An optics-based variable-temperature assay system for characterizing thermodynamics of biomolecular reactions on solid support

Energy Technology Data Exchange (ETDEWEB)

Fei, Yiyan; Landry, James P.; Zhu, X. D., E-mail: xdzhu@physics.ucdavis.edu [Department of Physics, University of California, One Shields Avenue, Davis, California 95616 (United States); Li, Yanhong; Yu, Hai; Lau, Kam; Huang, Shengshu; Chokhawala, Harshal A.; Chen, Xi [Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616 (United States)

2013-11-15

A biological state is equilibrium of multiple concurrent biomolecular reactions. The relative importance of these reactions depends on physiological temperature typically between 10 °C and 50 °C. Experimentally the temperature dependence of binding reaction constants reveals thermodynamics and thus details of these biomolecular processes. We developed a variable-temperature opto-fluidic system for real-time measurement of multiple (400–10 000) biomolecular binding reactions on solid supports from 10 °C to 60 °C within ±0.1 °C. We illustrate the performance of this system with investigation of binding reactions of plant lectins (carbohydrate-binding proteins) with 24 synthetic glycans (i.e., carbohydrates). We found that the lectin-glycan reactions in general can be enthalpy-driven, entropy-driven, or both, and water molecules play critical roles in the thermodynamics of these reactions.

A compact imaging spectroscopic system for biomolecular detections on plasmonic chips.

Science.gov (United States)

Lo, Shu-Cheng; Lin, En-Hung; Wei, Pei-Kuen; Tsai, Wan-Shao

2016-10-17

In this study, we demonstrate a compact imaging spectroscopic system for high-throughput detection of biomolecular interactions on plasmonic chips, based on a curved grating as the key element of light diffraction and light focusing. Both the curved grating and the plasmonic chips are fabricated on flexible plastic substrates using a gas-assisted thermal-embossing method. A fiber-coupled broadband light source and a camera are included in the system. Spectral resolution within 1 nm is achieved in sensing environmental index solutions and protein bindings. The detected sensitivities of the plasmonic chip are comparable with a commercial spectrometer. An extra one-dimensional scanning stage enables high-throughput detection of protein binding on a designed plasmonic chip consisting of several nanoslit arrays with different periods. The detected resonance wavelengths match well with the grating equation under an air environment. Wavelength shifts between 1 and 9 nm are detected for antigens of various concentrations binding with antibodies. A simple, mass-productive and cost-effective method has been demonstrated on the imaging spectroscopic system for real-time, label-free, highly sensitive and high-throughput screening of biomolecular interactions.

Improvements to the APBS biomolecular solvation software suite: Improvements to the APBS Software Suite

Energy Technology Data Exchange (ETDEWEB)

Jurrus, Elizabeth [Pacific Northwest National Laboratory, Richland Washington; Engel, Dave [Pacific Northwest National Laboratory, Richland Washington; Star, Keith [Pacific Northwest National Laboratory, Richland Washington; Monson, Kyle [Pacific Northwest National Laboratory, Richland Washington; Brandi, Juan [Pacific Northwest National Laboratory, Richland Washington; Felberg, Lisa E. [University of California, Berkeley California; Brookes, David H. [University of California, Berkeley California; Wilson, Leighton [University of Michigan, Ann Arbor Michigan; Chen, Jiahui [Southern Methodist University, Dallas Texas; Liles, Karina [Pacific Northwest National Laboratory, Richland Washington; Chun, Minju [Pacific Northwest National Laboratory, Richland Washington; Li, Peter [Pacific Northwest National Laboratory, Richland Washington; Gohara, David W. [St. Louis University, St. Louis Missouri; Dolinsky, Todd [FoodLogiQ, Durham North Carolina; Konecny, Robert [University of California San Diego, San Diego California; Koes, David R. [University of Pittsburgh, Pittsburgh Pennsylvania; Nielsen, Jens Erik [Protein Engineering, Novozymes A/S, Copenhagen Denmark; Head-Gordon, Teresa [University of California, Berkeley California; Geng, Weihua [Southern Methodist University, Dallas Texas; Krasny, Robert [University of Michigan, Ann Arbor Michigan; Wei, Guo-Wei [Michigan State University, East Lansing Michigan; Holst, Michael J. [University of California San Diego, San Diego California; McCammon, J. Andrew [University of California San Diego, San Diego California; Baker, Nathan A. [Pacific Northwest National Laboratory, Richland Washington; Brown University, Providence Rhode Island

2017-10-24

The Adaptive Poisson-Boltzmann Solver (APBS) software was developed to solve the equations of continuum electrostatics for large biomolecular assemblages that has provided impact in the study of a broad range of chemical, biological, and biomedical applications. APBS addresses three key technology challenges for understanding solvation and electrostatics in biomedical applications: accurate and efficient models for biomolecular solvation and electrostatics, robust and scalable software for applying those theories to biomolecular systems, and mechanisms for sharing and analyzing biomolecular electrostatics data in the scientific community. To address new research applications and advancing computational capabilities, we have continually updated APBS and its suite of accompanying software since its release in 2001. In this manuscript, we discuss the models and capabilities that have recently been implemented within the APBS software package including: a Poisson-Boltzmann analytical and a semi-analytical solver, an optimized boundary element solver, a geometry-based geometric flow solvation model, a graph theory based algorithm for determining pKa values, and an improved web-based visualization tool for viewing electrostatics.

Hybrid Quantum Mechanics/Molecular Mechanics/Coarse Grained Modeling: A Triple-Resolution Approach for Biomolecular Systems.

Science.gov (United States)

Sokkar, Pandian; Boulanger, Eliot; Thiel, Walter; Sanchez-Garcia, Elsa

2015-04-14

We present a hybrid quantum mechanics/molecular mechanics/coarse-grained (QM/MM/CG) multiresolution approach for solvated biomolecular systems. The chemically important active-site region is treated at the QM level. The biomolecular environment is described by an atomistic MM force field, and the solvent is modeled with the CG Martini force field using standard or polarizable (pol-CG) water. Interactions within the QM, MM, and CG regions, and between the QM and MM regions, are treated in the usual manner, whereas the CG-MM and CG-QM interactions are evaluated using the virtual sites approach. The accuracy and efficiency of our implementation is tested for two enzymes, chorismate mutase (CM) and p-hydroxybenzoate hydroxylase (PHBH). In CM, the QM/MM/CG potential energy scans along the reaction coordinate yield reaction energies that are too large, both for the standard and polarizable Martini CG water models, which can be attributed to adverse effects of using large CG water beads. The inclusion of an atomistic MM water layer (10 Å for uncharged CG water and 5 Å for polarizable CG water) around the QM region improves the energy profiles compared to the reference QM/MM calculations. In analogous QM/MM/CG calculations on PHBH, the use of the pol-CG description for the outer water does not affect the stabilization of the highly charged FADHOOH-pOHB transition state compared to the fully atomistic QM/MM calculations. Detailed performance analysis in a glycine-water model system indicates that computation times for QM energy and gradient evaluations at the density functional level are typically reduced by 40-70% for QM/MM/CG relative to fully atomistic QM/MM calculations.

Biomolecular Sciences: uniting Biology and Chemistry

NARCIS (Netherlands)

Vrieling, Engel

2017-01-01

Biomolecular Sciences: uniting Biology and Chemistry www.rug.nl/research/gbb The scientific discoveries in biomolecular sciences have benefitted enormously from technological innovations. At the Groningen Biomolecular Science and Biotechnology Institute (GBB) we now sequence a genome in days,

Rapid prototyping of nanofluidic systems using size-reduced electrospun nanofibers for biomolecular analysis.

Science.gov (United States)

Park, Seung-Min; Huh, Yun Suk; Szeto, Kylan; Joe, Daniel J; Kameoka, Jun; Coates, Geoffrey W; Edel, Joshua B; Erickson, David; Craighead, Harold G

2010-11-05

Biomolecular transport in nanofluidic confinement offers various means to investigate the behavior of biomolecules in their native aqueous environments, and to develop tools for diverse single-molecule manipulations. Recently, a number of simple nanofluidic fabrication techniques has been demonstrated that utilize electrospun nanofibers as a backbone structure. These techniques are limited by the arbitrary dimension of the resulting nanochannels due to the random nature of electrospinning. Here, a new method for fabricating nanofluidic systems from size-reduced electrospun nanofibers is reported and demonstrated. As it is demonstrated, this method uses the scanned electrospinning technique for generation of oriented sacrificial nanofibers and exposes these nanofibers to harsh, but isotropic etching/heating environments to reduce their cross-sectional dimension. The creation of various nanofluidic systems as small as 20 nm is demonstrated, and practical examples of single biomolecular handling, such as DNA elongation in nanochannels and fluorescence correlation spectroscopic analysis of biomolecules passing through nanochannels, are provided.

Introduction to a Protein Interaction System Used for Quantitative Evaluation of Biomolecular Interactions

OpenAIRE

Yamniuk, Aaron

2013-01-01

A central goal of molecular biology is the determination of biomolecular function. This comes largely from a knowledge of the non-covalent interactions that biological small and macro-molecules experience. The fundamental mission of the Molecular Interactions Research Group (MIRG) of the ABRF is to show how solution biophysical tools are used to quantitatively characterize molecular interactions, and to educate the ABRF members and scientific community on the utility and limitations of core t...

Membrane-based biomolecular smart materials

International Nuclear Information System (INIS)

Sarles, Stephen A; Leo, Donald J

2011-01-01

Membrane-based biomolecular materials are a new class of smart material that feature networks of artificial lipid bilayers contained within durable synthetic substrates. Bilayers contained within this modular material platform provide an environment that can be tailored to host an enormous diversity of functional biomolecules, where the functionality of the global material system depends on the type(s) and organization(s) of the biomolecules that are chosen. In this paper, we review a series of biomolecular material platforms developed recently within the Leo Group at Virginia Tech and we discuss several novel coupling mechanisms provided by these hybrid material systems. The platforms developed demonstrate that the functions of biomolecules and the properties of synthetic materials can be combined to operate in concert, and the examples provided demonstrate how the formation and properties of a lipid bilayer can respond to a variety of stimuli including mechanical forces and electric fields

New Distributed Multipole Methods for Accurate Electrostatics for Large-Scale Biomolecular Simultations

Science.gov (United States)

Sagui, Celeste

2006-03-01

An accurate and numerically efficient treatment of electrostatics is essential for biomolecular simulations, as this stabilizes much of the delicate 3-d structure associated with biomolecules. Currently, force fields such as AMBER and CHARMM assign ``partial charges'' to every atom in a simulation in order to model the interatomic electrostatic forces, so that the calculation of the electrostatics rapidly becomes the computational bottleneck in large-scale simulations. There are two main issues associated with the current treatment of classical electrostatics: (i) how does one eliminate the artifacts associated with the point-charges (e.g., the underdetermined nature of the current RESP fitting procedure for large, flexible molecules) used in the force fields in a physically meaningful way? (ii) how does one efficiently simulate the very costly long-range electrostatic interactions? Recently, we have dealt with both of these challenges as follows. In order to improve the description of the molecular electrostatic potentials (MEPs), a new distributed multipole analysis based on localized functions -- Wannier, Boys, and Edminston-Ruedenberg -- was introduced, which allows for a first principles calculation of the partial charges and multipoles. Through a suitable generalization of the particle mesh Ewald (PME) and multigrid method, one can treat electrostatic multipoles all the way to hexadecapoles all without prohibitive extra costs. The importance of these methods for large-scale simulations will be discussed, and examplified by simulations from polarizable DNA models.

Biomolecular electrostatics and solvation: a computational perspective.

Science.gov (United States)

Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G; Schnieders, Michael J; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A

2012-11-01

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view toward describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g. solvent structure, polarization, ion binding, and non-polar behavior) in order to provide a background to understand the different types of solvation models.

A compact hard X-ray source for medical imaging and biomolecular studies

International Nuclear Information System (INIS)

Cline, D.B.; Green, M.A.; Kolonko, J.

1995-01-01

There are a large number of synchrotron light sources in the world. However, these sources are designed for physics, chemistry, and engineering studies. To our knowledge, none have been optimized for either medical imaging or biomolecular studies. There are special needs for these applications. We present here a preliminary design of a very compact source, small enough for a hospital or a biomolecular laboratory, that is suitable for these applications. (orig.)

Biomolecular simulation: historical picture and future perspectives.

Science.gov (United States)

van Gunsteren, Wilfred F; Dolenc, Jozica

2008-02-01

Over the last 30 years, computation based on molecular models is playing an increasingly important role in biology, biological chemistry and biophysics. Since only a very limited number of properties of biomolecular systems are actually accessible to measurement by experimental means, computer simulation complements experiments by providing not only averages, but also distributions and time series of any definable, observable or non-observable, quantity. Biomolecular simulation may be used (i) to interpret experimental data, (ii) to provoke new experiments, (iii) to replace experiments and (iv) to protect intellectual property. Progress over the last 30 years is sketched and perspectives are outlined for the future.

Tailoring the Variational Implicit Solvent Method for New Challenges: Biomolecular Recognition and Assembly

Directory of Open Access Journals (Sweden)

Clarisse Gravina Ricci

2018-02-01

Full Text Available Predicting solvation free energies and describing the complex water behavior that plays an important role in essentially all biological processes is a major challenge from the computational standpoint. While an atomistic, explicit description of the solvent can turn out to be too expensive in large biomolecular systems, most implicit solvent methods fail to capture “dewetting” effects and heterogeneous hydration by relying on a pre-established (i.e., guessed solvation interface. Here we focus on the Variational Implicit Solvent Method, an implicit solvent method that adds water “plasticity” back to the picture by formulating the solvation free energy as a functional of all possible solvation interfaces. We survey VISM's applications to the problem of molecular recognition and report some of the most recent efforts to tailor VISM for more challenging scenarios, with the ultimate goal of including thermal fluctuations into the framework. The advances reported herein pave the way to make VISM a uniquely successful approach to characterize complex solvation properties in the recognition and binding of large-scale biomolecular complexes.

Tailoring the Variational Implicit Solvent Method for New Challenges: Biomolecular Recognition and Assembly

Science.gov (United States)

Ricci, Clarisse Gravina; Li, Bo; Cheng, Li-Tien; Dzubiella, Joachim; McCammon, J. Andrew

2018-01-01

Predicting solvation free energies and describing the complex water behavior that plays an important role in essentially all biological processes is a major challenge from the computational standpoint. While an atomistic, explicit description of the solvent can turn out to be too expensive in large biomolecular systems, most implicit solvent methods fail to capture “dewetting” effects and heterogeneous hydration by relying on a pre-established (i.e., guessed) solvation interface. Here we focus on the Variational Implicit Solvent Method, an implicit solvent method that adds water “plasticity” back to the picture by formulating the solvation free energy as a functional of all possible solvation interfaces. We survey VISM's applications to the problem of molecular recognition and report some of the most recent efforts to tailor VISM for more challenging scenarios, with the ultimate goal of including thermal fluctuations into the framework. The advances reported herein pave the way to make VISM a uniquely successful approach to characterize complex solvation properties in the recognition and binding of large-scale biomolecular complexes. PMID:29484300

A multiscale modeling approach for biomolecular systems

Energy Technology Data Exchange (ETDEWEB)

Bowling, Alan, E-mail: bowling@uta.edu; Haghshenas-Jaryani, Mahdi, E-mail: mahdi.haghshenasjaryani@mavs.uta.edu [The University of Texas at Arlington, Department of Mechanical and Aerospace Engineering (United States)

2015-04-15

This paper presents a new multiscale molecular dynamic model for investigating the effects of external interactions, such as contact and impact, during stepping and docking of motor proteins and other biomolecular systems. The model retains the mass properties ensuring that the result satisfies Newton’s second law. This idea is presented using a simple particle model to facilitate discussion of the rigid body model; however, the particle model does provide insights into particle dynamics at the nanoscale. The resulting three-dimensional model predicts a significant decrease in the effect of the random forces associated with Brownian motion. This conclusion runs contrary to the widely accepted notion that the motor protein’s movements are primarily the result of thermal effects. This work focuses on the mechanical aspects of protein locomotion; the effect ATP hydrolysis is estimated as internal forces acting on the mechanical model. In addition, the proposed model can be numerically integrated in a reasonable amount of time. Herein, the differences between the motion predicted by the old and new modeling approaches are compared using a simplified model of myosin V.

Modeling, Analysis, Simulation, and Synthesis of Biomolecular Networks

National Research Council Canada - National Science Library

Ruben, Harvey; Kumar, Vijay; Sokolsky, Oleg

2006-01-01

...) a first example of reachability analysis applied to a biomolecular system (lactose induction), 4) a model of tetracycline resistance that discriminates between two possible mechanisms for tetracycline diffusion through the cell membrane, and 5...

NMRbox: A Resource for Biomolecular NMR Computation.

Science.gov (United States)

Maciejewski, Mark W; Schuyler, Adam D; Gryk, Michael R; Moraru, Ion I; Romero, Pedro R; Ulrich, Eldon L; Eghbalnia, Hamid R; Livny, Miron; Delaglio, Frank; Hoch, Jeffrey C

2017-04-25

Advances in computation have been enabling many recent advances in biomolecular applications of NMR. Due to the wide diversity of applications of NMR, the number and variety of software packages for processing and analyzing NMR data is quite large, with labs relying on dozens, if not hundreds of software packages. Discovery, acquisition, installation, and maintenance of all these packages is a burdensome task. Because the majority of software packages originate in academic labs, persistence of the software is compromised when developers graduate, funding ceases, or investigators turn to other projects. To simplify access to and use of biomolecular NMR software, foster persistence, and enhance reproducibility of computational workflows, we have developed NMRbox, a shared resource for NMR software and computation. NMRbox employs virtualization to provide a comprehensive software environment preconfigured with hundreds of software packages, available as a downloadable virtual machine or as a Platform-as-a-Service supported by a dedicated compute cloud. Ongoing development includes a metadata harvester to regularize, annotate, and preserve workflows and facilitate and enhance data depositions to BioMagResBank, and tools for Bayesian inference to enhance the robustness and extensibility of computational analyses. In addition to facilitating use and preservation of the rich and dynamic software environment for biomolecular NMR, NMRbox fosters the development and deployment of a new class of metasoftware packages. NMRbox is freely available to not-for-profit users. Copyright © 2017 Biophysical Society. All rights reserved.

Bookshelf: a simple curation system for the storage of biomolecular simulation data.

Science.gov (United States)

Vohra, Shabana; Hall, Benjamin A; Holdbrook, Daniel A; Khalid, Syma; Biggin, Philip C

2010-01-01

Molecular dynamics simulations can now routinely generate data sets of several hundreds of gigabytes in size. The ability to generate this data has become easier over recent years and the rate of data production is likely to increase rapidly in the near future. One major problem associated with this vast amount of data is how to store it in a way that it can be easily retrieved at a later date. The obvious answer to this problem is a database. However, a key issue in the development and maintenance of such a database is its sustainability, which in turn depends on the ease of the deposition and retrieval process. Encouraging users to care about meta-data is difficult and thus the success of any storage system will ultimately depend on how well used by end-users the system is. In this respect we suggest that even a minimal amount of metadata if stored in a sensible fashion is useful, if only at the level of individual research groups. We discuss here, a simple database system which we call 'Bookshelf', that uses python in conjunction with a mysql database to provide an extremely simple system for curating and keeping track of molecular simulation data. It provides a user-friendly, scriptable solution to the common problem amongst biomolecular simulation laboratories; the storage, logging and subsequent retrieval of large numbers of simulations. Download URL: http://sbcb.bioch.ox.ac.uk/bookshelf/

Biomolecular engineering for nanobio/bionanotechnology

Science.gov (United States)

Nagamune, Teruyuki

2017-04-01

Biomolecular engineering can be used to purposefully manipulate biomolecules, such as peptides, proteins, nucleic acids and lipids, within the framework of the relations among their structures, functions and properties, as well as their applicability to such areas as developing novel biomaterials, biosensing, bioimaging, and clinical diagnostics and therapeutics. Nanotechnology can also be used to design and tune the sizes, shapes, properties and functionality of nanomaterials. As such, there are considerable overlaps between nanotechnology and biomolecular engineering, in that both are concerned with the structure and behavior of materials on the nanometer scale or smaller. Therefore, in combination with nanotechnology, biomolecular engineering is expected to open up new fields of nanobio/bionanotechnology and to contribute to the development of novel nanobiomaterials, nanobiodevices and nanobiosystems. This review highlights recent studies using engineered biological molecules (e.g., oligonucleotides, peptides, proteins, enzymes, polysaccharides, lipids, biological cofactors and ligands) combined with functional nanomaterials in nanobio/bionanotechnology applications, including therapeutics, diagnostics, biosensing, bioanalysis and biocatalysts. Furthermore, this review focuses on five areas of recent advances in biomolecular engineering: (a) nucleic acid engineering, (b) gene engineering, (c) protein engineering, (d) chemical and enzymatic conjugation technologies, and (e) linker engineering. Precisely engineered nanobiomaterials, nanobiodevices and nanobiosystems are anticipated to emerge as next-generation platforms for bioelectronics, biosensors, biocatalysts, molecular imaging modalities, biological actuators, and biomedical applications.

Stochastic Simulation of Biomolecular Reaction Networks Using the Biomolecular Network Simulator Software

National Research Council Canada - National Science Library

Frazier, John; Chusak, Yaroslav; Foy, Brent

2008-01-01

.... The software uses either exact or approximate stochastic simulation algorithms for generating Monte Carlo trajectories that describe the time evolution of the behavior of biomolecular reaction networks...

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

Science.gov (United States)

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

2013-01-01

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

A statistical nanomechanism of biomolecular patterning actuated by surface potential

Science.gov (United States)

Lin, Chih-Ting; Lin, Chih-Hao

2011-02-01

Biomolecular patterning on a nanoscale/microscale on chip surfaces is one of the most important techniques used in vitro biochip technologies. Here, we report upon a stochastic mechanics model we have developed for biomolecular patterning controlled by surface potential. The probabilistic biomolecular surface adsorption behavior can be modeled by considering the potential difference between the binding and nonbinding states. To verify our model, we experimentally implemented a method of electroactivated biomolecular patterning technology and the resulting fluorescence intensity matched the prediction of the developed model quite well. Based on this result, we also experimentally demonstrated the creation of a bovine serum albumin pattern with a width of 200 nm in 5 min operations. This submicron noncovalent-binding biomolecular pattern can be maintained for hours after removing the applied electrical voltage. These stochastic understandings and experimental results not only prove the feasibility of submicron biomolecular patterns on chips but also pave the way for nanoscale interfacial-bioelectrical engineering.

Thermodynamic properties of water solvating biomolecular surfaces

Science.gov (United States)

Heyden, Matthias

Changes in the potential energy and entropy of water molecules hydrating biomolecular interfaces play a significant role for biomolecular solubility and association. Free energy perturbation and thermodynamic integration methods allow calculations of free energy differences between two states from simulations. However, these methods are computationally demanding and do not provide insights into individual thermodynamic contributions, i.e. changes in the solvent energy or entropy. Here, we employ methods to spatially resolve distributions of hydration water thermodynamic properties in the vicinity of biomolecular surfaces. This allows direct insights into thermodynamic signatures of the hydration of hydrophobic and hydrophilic solvent accessible sites of proteins and small molecules and comparisons to ideal model surfaces. We correlate dynamic properties of hydration water molecules, i.e. translational and rotational mobility, to their thermodynamics. The latter can be used as a guide to extract thermodynamic information from experimental measurements of site-resolved water dynamics. Further, we study energy-entropy compensations of water at different hydration sites of biomolecular surfaces. This work is supported by the Cluster of Excellence RESOLV (EXC 1069) funded by the Deutsche Forschungsgemeinschaft.

Smartphones for cell and biomolecular detection.

Science.gov (United States)

Liu, Xiyuan; Lin, Tung-Yi; Lillehoj, Peter B

2014-11-01

Recent advances in biomedical science and technology have played a significant role in the development of new sensors and assays for cell and biomolecular detection. Generally, these efforts are aimed at reducing the complexity and costs associated with diagnostic testing so that it can be performed outside of a laboratory or hospital setting, requiring minimal equipment and user involvement. In particular, point-of-care (POC) testing offers immense potential for many important applications including medical diagnosis, environmental monitoring, food safety, and biosecurity. When coupled with smartphones, POC systems can offer portability, ease of use and enhanced functionality while maintaining performance. This review article focuses on recent advancements and developments in smartphone-based POC systems within the last 6 years with an emphasis on cell and biomolecular detection. These devices typically comprise multiple components, such as detectors, sample processors, disposable chips, batteries, and software, which are integrated with a commercial smartphone. One of the most important aspects of developing these systems is the integration of these components onto a compact and lightweight platform that requires minimal power. Researchers have demonstrated several promising approaches employing various detection schemes and device configurations, and it is expected that further developments in biosensors, battery technology and miniaturized electronics will enable smartphone-based POC technologies to become more mainstream tools in the scientific and biomedical communities.

Biomolecular condensates: organizers of cellular biochemistry.

Science.gov (United States)

Banani, Salman F; Lee, Hyun O; Hyman, Anthony A; Rosen, Michael K

2017-05-01

Biomolecular condensates are micron-scale compartments in eukaryotic cells that lack surrounding membranes but function to concentrate proteins and nucleic acids. These condensates are involved in diverse processes, including RNA metabolism, ribosome biogenesis, the DNA damage response and signal transduction. Recent studies have shown that liquid-liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates. With this physical framework, it is now possible to explain how the assembly, composition, physical properties and biochemical and cellular functions of these important structures are regulated.

Programming in biomolecular computation

DEFF Research Database (Denmark)

Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue

2011-01-01

Our goal is to provide a top-down approach to biomolecular computation. In spite of widespread discussion about connections between biology and computation, one question seems notable by its absence: Where are the programs? We identify a number of common features in programming that seem...... conspicuously absent from the literature on biomolecular computing; to partially redress this absence, we introduce a model of computation that is evidently programmable, by programs reminiscent of low-level computer machine code; and at the same time biologically plausible: its functioning is defined...... by a single and relatively small set of chemical-like reaction rules. Further properties: the model is stored-program: programs are the same as data, so programs are not only executable, but are also compilable and interpretable. It is universal: all computable functions can be computed (in natural ways...

iCAVE: an open source tool for visualizing biomolecular networks in 3D, stereoscopic 3D and immersive 3D.

Science.gov (United States)

Liluashvili, Vaja; Kalayci, Selim; Fluder, Eugene; Wilson, Manda; Gabow, Aaron; Gümüs, Zeynep H

2017-08-01

Visualizations of biomolecular networks assist in systems-level data exploration in many cellular processes. Data generated from high-throughput experiments increasingly inform these networks, yet current tools do not adequately scale with concomitant increase in their size and complexity. We present an open source software platform, interactome-CAVE (iCAVE), for visualizing large and complex biomolecular interaction networks in 3D. Users can explore networks (i) in 3D using a desktop, (ii) in stereoscopic 3D using 3D-vision glasses and a desktop, or (iii) in immersive 3D within a CAVE environment. iCAVE introduces 3D extensions of known 2D network layout, clustering, and edge-bundling algorithms, as well as new 3D network layout algorithms. Furthermore, users can simultaneously query several built-in databases within iCAVE for network generation or visualize their own networks (e.g., disease, drug, protein, metabolite). iCAVE has modular structure that allows rapid development by addition of algorithms, datasets, or features without affecting other parts of the code. Overall, iCAVE is the first freely available open source tool that enables 3D (optionally stereoscopic or immersive) visualizations of complex, dense, or multi-layered biomolecular networks. While primarily designed for researchers utilizing biomolecular networks, iCAVE can assist researchers in any field. © The Authors 2017. Published by Oxford University Press.

Biomolecular Structure Information from High-Speed Quantum Mechanical Electronic Spectra Calculation.

Science.gov (United States)

Seibert, Jakob; Bannwarth, Christoph; Grimme, Stefan

2017-08-30

A fully quantum mechanical (QM) treatment to calculate electronic absorption (UV-vis) and circular dichroism (CD) spectra of typical biomolecules with thousands of atoms is presented. With our highly efficient sTDA-xTB method, spectra averaged along structures from molecular dynamics (MD) simulations can be computed in a reasonable time frame on standard desktop computers. This way, nonequilibrium structure and conformational, as well as purely quantum mechanical effects like charge-transfer or exciton-coupling, are included. Different from other contemporary approaches, the entire system is treated quantum mechanically and neither fragmentation nor system-specific adjustment is necessary. Among the systems considered are a large DNA fragment, oligopeptides, and even entire proteins in an implicit solvent. We propose the method in tandem with experimental spectroscopy or X-ray studies for the elucidation of complex (bio)molecular structures including metallo-proteins like myoglobin.

Unique temporal and spatial biomolecular emission profile on individual zinc oxide nanorods

Science.gov (United States)

Singh, Manpreet; Song, Sheng; Hahm, Jong-In

2013-12-01

Zinc oxide nanorods (ZnO NRs) have emerged in recent years as extremely useful, optical signal-enhancing platforms in DNA and protein detection. Although the use of ZnO NRs in biodetection has been demonstrated so far in systems involving many ZnO NRs per detection element, their future applications will likely take place in a miniaturized setting while exploiting single ZnO NRs in a low-volume, high-throughput bioanalysis. In this paper, we investigate temporal and spatial characteristics of the biomolecular fluorescence on individual ZnO NR systems. Quantitative and qualitative examinations of the biomolecular intensity and photostability are carried out as a function of two important criteria, the time and position along the long axis (length) of NRs. Photostability profiles are also measured with respect to the position on NRs and compared to those characteristics of biomolecules on polymeric control platforms. Unlike the uniformly distributed signal observed on the control platforms, both the fluorescence intensity and photostability are position-dependent on individual ZnO NRs. We have identified a unique phenomenon of highly localized, fluorescence intensification on the nanorod ends (FINE) of well-characterized, individual ZnO nanostructures. When compared to the polymeric controls, the biomolecular fluorescence intensity and photostability are determined to be higher on individual ZnO NRs regardless of the position on NRs. We have also carried out finite-difference time-domain simulations the results of which are in good agreement with the observed FINE. The outcomes of our investigation will offer a much needed basis for signal interpretation for biodetection devices and platforms consisting of single ZnO NRs and, at the same time, contribute significantly to provide insight in understanding the biomolecular fluorescence observed from ZnO NR ensemble-based systems.Zinc oxide nanorods (ZnO NRs) have emerged in recent years as extremely useful, optical

Electrochemical sensor for multiplex screening of genetically modified DNA: identification of biotech crops by logic-based biomolecular analysis.

Science.gov (United States)

Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie

2013-12-15

Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.

Synthetic Approach to biomolecular science by cyborg supramolecular chemistry.

Science.gov (United States)

Kurihara, Kensuke; Matsuo, Muneyuki; Yamaguchi, Takumi; Sato, Sota

2018-02-01

To imitate the essence of living systems via synthetic chemistry approaches has been attempted. With the progress in supramolecular chemistry, it has become possible to synthesize molecules of a size and complexity close to those of biomacromolecules. Recently, the combination of precisely designed supramolecules with biomolecules has generated structural platforms for designing and creating unique molecular systems. Bridging between synthetic chemistry and biomolecular science is also developing methodologies for the creation of artificial cellular systems. This paper provides an overview of the recently expanding interdisciplinary research to fuse artificial molecules with biomolecules, that can deepen our understanding of the dynamical ordering of biomolecules. Using bottom-up approaches based on the precise chemical design, synthesis and hybridization of artificial molecules with biological materials have been realizing the construction of sophisticated platforms having the fundamental functions of living systems. The effective hybrid, molecular cyborg, approaches enable not only the establishment of dynamic systems mimicking nature and thus well-defined models for biophysical understanding, but also the creation of those with highly advanced, integrated functions. This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. Copyright © 2017 Elsevier B.V. All rights reserved.

A fast mollified impulse method for biomolecular atomistic simulations

Energy Technology Data Exchange (ETDEWEB)

Fath, L., E-mail: lukas.fath@kit.edu [Institute for App. and Num. Mathematics, Karlsruhe Institute of Technology (Germany); Hochbruck, M., E-mail: marlis.hochbruck@kit.edu [Institute for App. and Num. Mathematics, Karlsruhe Institute of Technology (Germany); Singh, C.V., E-mail: chandraveer.singh@utoronto.ca [Department of Materials Science & Engineering, University of Toronto (Canada)

2017-03-15

Classical integration methods for molecular dynamics are inherently limited due to resonance phenomena occurring at certain time-step sizes. The mollified impulse method can partially avoid this problem by using appropriate filters based on averaging or projection techniques. However, existing filters are computationally expensive and tedious in implementation since they require either analytical Hessians or they need to solve nonlinear systems from constraints. In this work we follow a different approach based on corotation for the construction of a new filter for (flexible) biomolecular simulations. The main advantages of the proposed filter are its excellent stability properties and ease of implementation in standard softwares without Hessians or solving constraint systems. By simulating multiple realistic examples such as peptide, protein, ice equilibrium and ice–ice friction, the new filter is shown to speed up the computations of long-range interactions by approximately 20%. The proposed filtered integrators allow step sizes as large as 10 fs while keeping the energy drift less than 1% on a 50 ps simulation.

REVIEW ARTICLE: How do biomolecular systems speed up and regulate rates?

Science.gov (United States)

Zhou, Huan-Xiang

2005-09-01

The viability of a biological system depends upon careful regulation of the rates of various processes. These rates have limits imposed by intrinsic chemical or physical steps (e.g., diffusion). These limits can be expanded by interactions and dynamics of the biomolecules. For example, (a) a chemical reaction is catalyzed when its transition state is preferentially bound to an enzyme; (b) the folding of a protein molecule is speeded up by specific interactions within the transition-state ensemble and may be assisted by molecular chaperones; (c) the rate of specific binding of a protein molecule to a cellular target can be enhanced by mechanisms such as long-range electrostatic interactions, nonspecific binding and folding upon binding; (d) directional movement of motor proteins is generated by capturing favorable Brownian motion through intermolecular binding energy; and (e) conduction and selectivity of ions through membrane channels are controlled by interactions and the dynamics of channel proteins. Simple physical models are presented here to illustrate these processes and provide a unifying framework for understanding speed attainment and regulation in biomolecular systems.

Application of Hidden Markov Models in Biomolecular Simulations.

Science.gov (United States)

Shukla, Saurabh; Shamsi, Zahra; Moffett, Alexander S; Selvam, Balaji; Shukla, Diwakar

2017-01-01

Hidden Markov models (HMMs) provide a framework to analyze large trajectories of biomolecular simulation datasets. HMMs decompose the conformational space of a biological molecule into finite number of states that interconvert among each other with certain rates. HMMs simplify long timescale trajectories for human comprehension, and allow comparison of simulations with experimental data. In this chapter, we provide an overview of building HMMs for analyzing bimolecular simulation datasets. We demonstrate the procedure for building a Hidden Markov model for Met-enkephalin peptide simulation dataset and compare the timescales of the process.

hPDB – Haskell library for processing atomic biomolecular structures in protein data bank format

OpenAIRE

Gajda, Michał Jan

2013-01-01

Background Protein DataBank file format is used for the majority of biomolecular data available today. Haskell is a lazy functional language that enjoys a high-level class-based type system, a growing collection of useful libraries and a reputation for efficiency. Findings I present a fast library for processing biomolecular data in the Protein Data Bank format. I present benchmarks indicating that this library is faster than other frequently used Protein Data Bank parsing programs. The propo...

THz time domain spectroscopy of biomolecular conformational modes

International Nuclear Information System (INIS)

Markelz, Andrea; Whitmire, Scott; Hillebrecht, Jay; Birge, Robert

2002-01-01

We discuss the use of terahertz time domain spectroscopy for studies of conformational flexibility and conformational change in biomolecules. Protein structural dynamics are vital to biological function with protein flexibility affecting enzymatic reaction rates and sensory transduction cycling times. Conformational mode dynamics occur on the picosecond timescale and with the collective vibrational modes associated with these large scale structural motions in the 1-100 cm -1 range. We have performed THz time domain spectroscopy (TTDS) of several biomolecular systems to explore the sensitivity of TTDS to distinguish different molecular species, different mutations within a single species and different conformations of a given biomolecule. We compare the measured absorbances to normal mode calculations and find that the TTDS absorbance reflects the density of normal modes determined by molecular mechanics calculations, and is sensitive to both conformation and mutation. These early studies demonstrate some of the advantages and limitations of using TTDS for the study of biomolecules

Micro and Nanotechnologies Enhanced Biomolecular Sensing

Directory of Open Access Journals (Sweden)

Tza-Huei Wang

2013-07-01

Full Text Available This editorial summarizes some of the recent advances of micro and nanotechnology-based tools and devices for biomolecular detection. These include the incorporation of nanomaterials into a sensor surface or directly interfacing with molecular probes to enhance target detection via more rapid and sensitive responses, and the use of self-assembled organic/inorganic nanocomposites that inhibit exceptional spectroscopic properties to enable facile homogenous assays with efficient binding kinetics. Discussions also include some insight into microfluidic principles behind the development of an integrated sample preparation and biosensor platform toward a miniaturized and fully functional system for point of care applications.

Conducting polymer based biomolecular electronic devices

Indian Academy of Sciences (India)

Conducting polymers; LB films; biosensor microactuators; monolayers. ... have been projected for applications for a wide range of biomolecular electronic devices such as optical, electronic, drug-delivery, memory and biosensing devices.

Biomolecular simulations on petascale: promises and challenges

International Nuclear Information System (INIS)

Agarwal, Pratul K; Alam, Sadaf R

2006-01-01

Proteins work as highly efficient machines at the molecular level and are responsible for a variety of processes in all living cells. There is wide interest in understanding these machines for implications in biochemical/biotechnology industries as well as in health related fields. Over the last century, investigations of proteins based on a variety of experimental techniques have provided a wealth of information. More recently, theoretical and computational modeling using large scale simulations is providing novel insights into the functioning of these machines. The next generation supercomputers with petascale computing power, hold great promises as well as challenges for the biomolecular simulation scientists. We briefly discuss the progress being made in this area

Perspective: Markov models for long-timescale biomolecular dynamics

International Nuclear Information System (INIS)

Schwantes, C. R.; McGibbon, R. T.; Pande, V. S.

2014-01-01

Molecular dynamics simulations have the potential to provide atomic-level detail and insight to important questions in chemical physics that cannot be observed in typical experiments. However, simply generating a long trajectory is insufficient, as researchers must be able to transform the data in a simulation trajectory into specific scientific insights. Although this analysis step has often been taken for granted, it deserves further attention as large-scale simulations become increasingly routine. In this perspective, we discuss the application of Markov models to the analysis of large-scale biomolecular simulations. We draw attention to recent improvements in the construction of these models as well as several important open issues. In addition, we highlight recent theoretical advances that pave the way for a new generation of models of molecular kinetics

Perspective: Markov models for long-timescale biomolecular dynamics

Energy Technology Data Exchange (ETDEWEB)

Schwantes, C. R.; McGibbon, R. T. [Department of Chemistry, Stanford University, Stanford, California 94305 (United States); Pande, V. S., E-mail: pande@stanford.edu [Department of Chemistry, Stanford University, Stanford, California 94305 (United States); Department of Computer Science, Stanford University, Stanford, California 94305 (United States); Department of Structural Biology, Stanford University, Stanford, California 94305 (United States); Biophysics Program, Stanford University, Stanford, California 94305 (United States)

2014-09-07

Molecular dynamics simulations have the potential to provide atomic-level detail and insight to important questions in chemical physics that cannot be observed in typical experiments. However, simply generating a long trajectory is insufficient, as researchers must be able to transform the data in a simulation trajectory into specific scientific insights. Although this analysis step has often been taken for granted, it deserves further attention as large-scale simulations become increasingly routine. In this perspective, we discuss the application of Markov models to the analysis of large-scale biomolecular simulations. We draw attention to recent improvements in the construction of these models as well as several important open issues. In addition, we highlight recent theoretical advances that pave the way for a new generation of models of molecular kinetics.

Evolution of biomolecular loadings along a major river system

Science.gov (United States)

Freymond, Chantal V.; Kündig, Nicole; Stark, Courcelle; Peterse, Francien; Buggle, Björn; Lupker, Maarten; Plötze, Michael; Blattmann, Thomas M.; Filip, Florin; Giosan, Liviu; Eglinton, Timothy I.

2018-02-01

Understanding the transport history and fate of organic carbon (OC) within river systems is crucial in order to constrain the dynamics and significance of land-ocean interactions as a component of the global carbon cycle. Fluvial export and burial of terrestrial OC in marine sediments influences atmospheric CO2 over a range of timescales, while river-dominated sedimentary sequences can provide valuable archives of paleoenvironmental information. While there is abundant evidence that the association of organic matter (OM) with minerals exerts an important influence on its stability as well as hydrodynamic behavior in aquatic systems, there is a paucity of information on where such associations form and how they evolve during fluvial transport. Here, we track total organic carbon (TOC) and terrestrial biomarker concentrations (plant wax-derived long-chain fatty acids (FA), branched glycerol dialkyl glycerol tetraethers (brGDGTs) and lignin-derived phenols) in sediments collected along the entire course of the Danube River system in the context of sedimentological parameters. Mineral-specific surface area-normalized biomarker and TOC concentrations show a systematic decrease from the upper to the lower Danube basin. Changes in OM loading of the available mineral phase correspond to a net decrease of 70-80% of different biomolecular components. Ranges for biomarker loadings on Danube River sediments, corresponding to 0.4-1.5 μgFA/m2 for long-chain (n-C24-32) fatty acids and 17-71 ngbrGDGT/m2 for brGDGTs, are proposed as a benchmark for comparison with other systems. We propose that normalizing TOC as well as biomarker concentrations to mineral surface area provides valuable quantitative constraints on OM dynamics and organo-mineral interactions during fluvial transport from terrigenous source to oceanic sink.

Application of biomolecular recognition via magnetic nanoparticle in nanobiotechnology

Science.gov (United States)

Shen, Wei-Zheng; Cetinel, Sibel; Montemagno, Carlo

2018-05-01

The marriage of biomolecular recognition and magnetic nanoparticle creates tremendous opportunities in the development of advanced technology both in academic research and in industrial sectors. In this paper, we review current progress on the magnetic nanoparticle-biomolecule hybrid systems, particularly employing the recognition pairs of DNA-DNA, DNA-protein, protein-protein, and protein-inorganics in several nanobiotechnology application areas, including molecular biology, diagnostics, medical treatment, industrial biocatalysts, and environmental separations.

A model system for targeted drug release triggered by biomolecular signals logically processed through enzyme logic networks.

Science.gov (United States)

Mailloux, Shay; Halámek, Jan; Katz, Evgeny

2014-03-07

A new Sense-and-Act system was realized by the integration of a biocomputing system, performing analytical processes, with a signal-responsive electrode. A drug-mimicking release process was triggered by biomolecular signals processed by different logic networks, including three concatenated AND logic gates or a 3-input OR logic gate. Biocatalytically produced NADH, controlled by various combinations of input signals, was used to activate the electrochemical system. A biocatalytic electrode associated with signal-processing "biocomputing" systems was electrically connected to another electrode coated with a polymer film, which was dissolved upon the formation of negative potential releasing entrapped drug-mimicking species, an enzyme-antibody conjugate, operating as a model for targeted immune-delivery and consequent "prodrug" activation. The system offers great versatility for future applications in controlled drug release and personalized medicine.

HPDB-Haskell library for processing atomic biomolecular structures in Protein Data Bank format.

Science.gov (United States)

Gajda, Michał Jan

2013-11-23

Protein DataBank file format is used for the majority of biomolecular data available today. Haskell is a lazy functional language that enjoys a high-level class-based type system, a growing collection of useful libraries and a reputation for efficiency. I present a fast library for processing biomolecular data in the Protein Data Bank format. I present benchmarks indicating that this library is faster than other frequently used Protein Data Bank parsing programs. The proposed library also features a convenient iterator mechanism, and a simple API modeled after BioPython. I set a new standard for convenience and efficiency of Protein Data Bank processing in a Haskell library, and release it to open source.

Coupling switches and oscillators as a means to shape cellular signals in biomolecular systems

International Nuclear Information System (INIS)

Zhou, Peipei; Cai, Shuiming; Liu, Zengrong; Chen, Luonan; Wang, Ruiqi

2013-01-01

To understand how a complex biomolecular network functions, a decomposition or a reconstruction process of the network is often needed so as to provide new insights into the regulatory mechanisms underlying various dynamical behaviors and also to gain qualitative knowledge of the network. Unfortunately, it seems that there are still no general rules on how to decompose a complex network into simple modules. An alternative resolution is to decompose a complex network into small modules or subsystems with specified functions such as switches and oscillators and then integrate them by analyzing the interactions between them. The main idea of this approach can be illustrated by considering a bidirectionally coupled network in this paper, i.e., coupled Toggle switch and Repressilator, and analyzing the occurrence of various dynamics, although the theoretical principle may hold for a general class of networks. We show that various biomolecular signals can be shaped by regulating the coupling between the subsystems. The approach presented here can be expected to simplify and analyze even more complex biological networks

Coupling switches and oscillators as a means to shape cellular signals in biomolecular systems

Energy Technology Data Exchange (ETDEWEB)

Zhou, Peipei [Institute of Systems Biology, Shanghai University, Shanghai 200444 (China); Faculty of Science, Jiangsu University, Zhenjiang, Jiangsu 212013 (China); Cai, Shuiming [Faculty of Science, Jiangsu University, Zhenjiang, Jiangsu 212013 (China); Liu, Zengrong [Institute of Systems Biology, Shanghai University, Shanghai 200444 (China); Chen, Luonan [Key Laboratory of Systems Biology, SIBS-Novo Nordisk Translational Research Center for PreDiabetes, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Collaborative Research Center for Innovative Mathematical Modeling, Institute of Industrial Science, University of Tokyo, Tokyo 153-8505 (Japan); Wang, Ruiqi [Institute of Systems Biology, Shanghai University, Shanghai 200444 (China)

2013-05-15

To understand how a complex biomolecular network functions, a decomposition or a reconstruction process of the network is often needed so as to provide new insights into the regulatory mechanisms underlying various dynamical behaviors and also to gain qualitative knowledge of the network. Unfortunately, it seems that there are still no general rules on how to decompose a complex network into simple modules. An alternative resolution is to decompose a complex network into small modules or subsystems with specified functions such as switches and oscillators and then integrate them by analyzing the interactions between them. The main idea of this approach can be illustrated by considering a bidirectionally coupled network in this paper, i.e., coupled Toggle switch and Repressilator, and analyzing the occurrence of various dynamics, although the theoretical principle may hold for a general class of networks. We show that various biomolecular signals can be shaped by regulating the coupling between the subsystems. The approach presented here can be expected to simplify and analyze even more complex biological networks.

Application of Nanodiamonds in Biomolecular Mass Spectrometry

Directory of Open Access Journals (Sweden)

Ping Cheng

2010-03-01

Full Text Available The combination of nanodiamond (ND with biomolecular mass spectrometry (MS makes rapid, sensitive detection of biopolymers from complex biosamples feasible. Due to its chemical inertness, optical transparency and biocompatibility, the advantage of NDs in MS study is unique. Furthermore, functionalization on the surfaces of NDs expands their application in the fields of proteomics and genomics for specific requirements greatly. This review presents methods of MS analysis based on solid phase extraction and elution on NDs and different application examples including peptide, protein, DNA, glycan and others. Owing to the quick development of nanotechnology, surface chemistry, new MS methods and the intense interest in proteomics and genomics, a huge increase of their applications in biomolecular MS analysis in the near future can be predicted.

MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations.

Science.gov (United States)

Vergara-Perez, Sandra; Marucho, Marcelo

2016-01-01

One of the most used and efficient approaches to compute electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation. There are several software packages available that solve the PB equation for molecules in aqueous electrolyte solutions. Most of these software packages are useful for scientists with specialized training and expertise in computational biophysics. However, the user is usually required to manually take several important choices, depending on the complexity of the biological system, to successfully obtain the numerical solution of the PB equation. This may become an obstacle for researchers, experimentalists, even students with no special training in computational methodologies. Aiming to overcome this limitation, in this article we present MPBEC, a free, cross-platform, open-source software that provides non-experts in the field an easy and efficient way to perform biomolecular electrostatic calculations on single processor computers. MPBEC is a Matlab script based on the Adaptative Poisson Boltzmann Solver, one of the most popular approaches used to solve the PB equation. MPBEC does not require any user programming, text editing or extensive statistical skills, and comes with detailed user-guide documentation. As a unique feature, MPBEC includes a useful graphical user interface (GUI) application which helps and guides users to configure and setup the optimal parameters and approximations to successfully perform the required biomolecular electrostatic calculations. The GUI also incorporates visualization tools to facilitate users pre- and post- analysis of structural and electrical properties of biomolecules.

MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations

Science.gov (United States)

Vergara-Perez, Sandra; Marucho, Marcelo

2016-01-01

One of the most used and efficient approaches to compute electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation. There are several software packages available that solve the PB equation for molecules in aqueous electrolyte solutions. Most of these software packages are useful for scientists with specialized training and expertise in computational biophysics. However, the user is usually required to manually take several important choices, depending on the complexity of the biological system, to successfully obtain the numerical solution of the PB equation. This may become an obstacle for researchers, experimentalists, even students with no special training in computational methodologies. Aiming to overcome this limitation, in this article we present MPBEC, a free, cross-platform, open-source software that provides non-experts in the field an easy and efficient way to perform biomolecular electrostatic calculations on single processor computers. MPBEC is a Matlab script based on the Adaptative Poisson-Boltzmann Solver, one of the most popular approaches used to solve the PB equation. MPBEC does not require any user programming, text editing or extensive statistical skills, and comes with detailed user-guide documentation. As a unique feature, MPBEC includes a useful graphical user interface (GUI) application which helps and guides users to configure and setup the optimal parameters and approximations to successfully perform the required biomolecular electrostatic calculations. The GUI also incorporates visualization tools to facilitate users pre- and post-analysis of structural and electrical properties of biomolecules.

Laser photodissociation and spectroscopy of mass-separated biomolecular ions

CERN Document Server

Polfer, Nicolas C

2014-01-01

This lecture notes book presents how enhanced structural information of biomolecular ions can be obtained from interaction with photons of specific frequency - laser light. The methods described in the book ""Laser photodissociation and spectroscopy of mass-separated biomolecular ions"" make use of the fact that the discrete energy and fast time scale of photoexcitation can provide more control in ion activation. This activation is the crucial process producing structure-informative product ions that cannot be generated with more conventional heating methods, such as collisional activation. Th

Engineering intracellular active transport systems as in vivo biomolecular tools.

Energy Technology Data Exchange (ETDEWEB)

Bachand, George David; Carroll-Portillo, Amanda

2006-11-01

Active transport systems provide essential functions in terms of cell physiology and metastasis. These systems, however, are also co-opted by invading viruses, enabling directed transport of the virus to and from the cell's nucleus (i.e., the site of virus replication). Based on this concept, fundamentally new approaches for interrogating and manipulating the inner workings of living cells may be achievable by co-opting Nature's active transport systems as an in vivo biomolecular tool. The overall goal of this project was to investigate the ability to engineer kinesin-based transport systems for in vivo applications, specifically the collection of effector proteins (e.g., transcriptional regulators) within single cells. In the first part of this project, a chimeric fusion protein consisting of kinesin and a single chain variable fragment (scFv) of an antibody was successfully produced through a recombinant expression system. The kinesin-scFv retained both catalytic and antigenic functionality, enabling selective capture and transport of target antigens. The incorporation of a rabbit IgG-specific scFv into the kinesin established a generalized system for functionalizing kinesin with a wide range of target-selective antibodies raised in rabbits. The second objective was to develop methods of isolating the intact microtubule network from live cells as a platform for evaluating kinesin-based transport within the cytoskeletal architecture of a cell. Successful isolation of intact microtubule networks from two distinct cell types was demonstrated using glutaraldehyde and methanol fixation methods. This work provides a platform for inferring the ability of kinesin-scFv to function in vivo, and may also serve as a three-dimensional scaffold for evaluating and exploiting kinesin-based transport for nanotechnological applications. Overall, the technology developed in this project represents a first-step in engineering active transport system for in vivo

Dynamic and label-free high-throughput detection of biomolecular interactions based on phase-shift interferometry

Science.gov (United States)

Li, Qiang; Huang, Guoliang; Gan, Wupeng; Chen, Shengyi

2009-08-01

Biomolecular interactions can be detected by many established technologies such as fluorescence imaging, surface plasmon resonance (SPR)[1-4], interferometry and radioactive labeling of the analyte. In this study, we have designed and constructed a label-free, real-time sensing platform and its operating imaging instrument that detects interactions using optical phase differences from the accumulation of biological material on solid substrates. This system allows us to monitor biomolecular interactions in real time and quantify concentration changes during micro-mixing processes by measuring the changes of the optical path length (OPD). This simple interferometric technology monitors the optical phase difference resulting from accumulated biomolecular mass. A label-free protein chip that forms a 4×4 probe array was designed and fabricated using a commercial microarray robot spotter on solid substrates. Two positive control probe lines of BSA (Bovine Serum Albumin) and two experimental human IgG and goat IgG was used. The binding of multiple protein targets was performed and continuously detected by using this label-free and real-time sensing platform.

Techniques of biomolecular quantification through AMS detection of radiocarbon

International Nuclear Information System (INIS)

Vogel, S.J.; Turteltaub, K.W.; Frantz, C.; Felton, J.S.; Gledhill, B.L.

1992-01-01

Accelerator mass spectrometry offers a large gain over scintillation counting in sensitivity for detecting radiocarbon in biomolecular tracing. Application of this sensitivity requires new considerations of procedures to extract or isolate the carbon fraction to be quantified, to inventory all carbon in the sample, to prepare graphite from the sample for use in the spectrometer, and to derive a meaningful quantification from the measured isotope ratio. These procedures need to be accomplished without contaminating the sample with radiocarbon, which may be ubiquitous in laboratories and on equipment previously used for higher dose, scintillation experiments. Disposable equipment, materials and surfaces are used to control these contaminations. Quantification of attomole amounts of labeled substances are possible through these techniques

Biomolecular modelling and simulations

CERN Document Server

Karabencheva-Christova, Tatyana

2014-01-01

Published continuously since 1944, the Advances in Protein Chemistry and Structural Biology series is the essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins. Each thematically organized volume is guest edited by leading experts in a broad range of protein-related topics. Describes advances in biomolecular modelling and simulations Chapters are written by authorities in their field Targeted to a wide audience of researchers, specialists, and students The information provided in the volume is well supported by a number of high quality illustrations, figures, and tables.

Biomolecular structure refinement using the GROMOS simulation software

International Nuclear Information System (INIS)

Schmid, Nathan; Allison, Jane R.; Dolenc, Jožica; Eichenberger, Andreas P.; Kunz, Anna-Pitschna E.; Gunsteren, Wilfred F. van

2011-01-01

For the understanding of cellular processes the molecular structure of biomolecules has to be accurately determined. Initial models can be significantly improved by structure refinement techniques. Here, we present the refinement methods and analysis techniques implemented in the GROMOS software for biomolecular simulation. The methodology and some implementation details of the computation of NMR NOE data, 3 J-couplings and residual dipolar couplings, X-ray scattering intensities from crystals and solutions and neutron scattering intensities used in GROMOS is described and refinement strategies and concepts are discussed using example applications. The GROMOS software allows structure refinement combining different types of experimental data with different types of restraining functions, while using a variety of methods to enhance conformational searching and sampling and the thermodynamically calibrated GROMOS force field for biomolecular simulation.

Biomolecular structure refinement using the GROMOS simulation software

Energy Technology Data Exchange (ETDEWEB)

Schmid, Nathan; Allison, Jane R.; Dolenc, Jozica; Eichenberger, Andreas P.; Kunz, Anna-Pitschna E.; Gunsteren, Wilfred F. van, E-mail: wfvgn@igc.phys.chem.ethz.ch [Swiss Federal Institute of Technology ETH, Laboratory of Physical Chemistry (Switzerland)

2011-11-15

For the understanding of cellular processes the molecular structure of biomolecules has to be accurately determined. Initial models can be significantly improved by structure refinement techniques. Here, we present the refinement methods and analysis techniques implemented in the GROMOS software for biomolecular simulation. The methodology and some implementation details of the computation of NMR NOE data, {sup 3}J-couplings and residual dipolar couplings, X-ray scattering intensities from crystals and solutions and neutron scattering intensities used in GROMOS is described and refinement strategies and concepts are discussed using example applications. The GROMOS software allows structure refinement combining different types of experimental data with different types of restraining functions, while using a variety of methods to enhance conformational searching and sampling and the thermodynamically calibrated GROMOS force field for biomolecular simulation.

An effective hierarchical model for the biomolecular covalent bond: an approach integrating artificial chemistry and an actual terrestrial life system.

Science.gov (United States)

Oohashi, Tsutomu; Ueno, Osamu; Maekawa, Tadao; Kawai, Norie; Nishina, Emi; Honda, Manabu

2009-01-01

Under the AChem paradigm and the programmed self-decomposition (PSD) model, we propose a hierarchical model for the biomolecular covalent bond (HBCB model). This model assumes that terrestrial organisms arrange their biomolecules in a hierarchical structure according to the energy strength of their covalent bonds. It also assumes that they have evolutionarily selected the PSD mechanism of turning biological polymers (BPs) into biological monomers (BMs) as an efficient biomolecular recycling strategy We have examined the validity and effectiveness of the HBCB model by coordinating two complementary approaches: biological experiments using existent terrestrial life, and simulation experiments using an AChem system. Biological experiments have shown that terrestrial life possesses a PSD mechanism as an endergonic, genetically regulated process and that hydrolysis, which decomposes a BP into BMs, is one of the main processes of such a mechanism. In simulation experiments, we compared different virtual self-decomposition processes. The virtual species in which the self-decomposition process mainly involved covalent bond cleavage from a BP to BMs showed evolutionary superiority over other species in which the self-decomposition process involved cleavage from BP to classes lower than BM. These converging findings strongly support the existence of PSD and the validity and effectiveness of the HBCB model.

The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

Directory of Open Access Journals (Sweden)

Giulio Caravagna

Full Text Available After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii a model of enzymatic futile cycle and (iii a genetic toggle switch. In (ii and (iii we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.

The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

Science.gov (United States)

Caravagna, Giulio; Mauri, Giancarlo; d'Onofrio, Alberto

2013-01-01

After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i) the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii) a model of enzymatic futile cycle and (iii) a genetic toggle switch. In (ii) and (iii) we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.

Nanogap biosensors for electrical and label-free detection of biomolecular interactions

International Nuclear Information System (INIS)

Kyu Kim, Sang; Cho, Hyunmin; Park, Hye-Jung; Kwon, Dohyoung; Min Lee, Jeong; Hyun Chung, Bong

2009-01-01

We demonstrate nanogap biosensors for electrical and label-free detection of biomolecular interactions. Parallel fabrication of nanometer distance gaps has been achieved using a silicon anisotropic wet etching technique on a silicon-on-insulator (SOI) wafer with a finely controllable silicon device layer. Since silicon anisotropic wet etching resulted in a trapezoid-shaped structure whose end became narrower during the etching, the nanogap structure was simply fabricated on the device layer of a SOI wafer. The nanogap devices were individually addressable and a gap size of less than 60 nm was obtained. We demonstrate that the nanogap biosensors can electrically detect biomolecular interactions such as biotin/streptavidin and antigen/antibody pairs. The nanogap devices show a current increase when the proteins are bound to the surface. The current increases proportionally depending upon the concentrations of the molecules in the range of 100 fg ml -1 -100 ng ml -1 at 1 V bias. It is expected that the nanogap developed here could be a highly sensitive biosensor platform for label-free detection of biomolecular interactions.

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

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Shannon, Paul; Markiel, Andrew; Ozier, Owen; Baliga, Nitin S; Wang, Jonathan T; Ramage, Daniel; Amin, Nada; Schwikowski, Benno; Ideker, Trey

2003-11-01

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

Selected topics in solution-phase biomolecular NMR spectroscopy

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Kay, Lewis E.; Frydman, Lucio

2017-05-01

Solution bio-NMR spectroscopy continues to enjoy a preeminent role as an important tool in elucidating the structure and dynamics of a range of important biomolecules and in relating these to function. Equally impressive is how NMR continues to 'reinvent' itself through the efforts of many brilliant practitioners who ask increasingly demanding and increasingly biologically relevant questions. The ability to manipulate spin Hamiltonians - almost at will - to dissect the information of interest contributes to the success of the endeavor and ensures that the NMR technology will be well poised to contribute to as yet unknown frontiers in the future. As a tribute to the versatility of solution NMR in biomolecular studies and to the continued rapid advances in the field we present a Virtual Special Issue (VSI) that includes over 40 articles on various aspects of solution-state biomolecular NMR that have been published in the Journal of Magnetic Resonance in the past 7 years. These, in total, help celebrate the achievements of this vibrant field.

Biomolecular surface construction by PDE transform.

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Zheng, Qiong; Yang, Siyang; Wei, Guo-Wei

2012-03-01

This work proposes a new framework for the surface generation based on the partial differential equation (PDE) transform. The PDE transform has recently been introduced as a general approach for the mode decomposition of images, signals, and data. It relies on the use of arbitrarily high-order PDEs to achieve the time-frequency localization, control the spectral distribution, and regulate the spatial resolution. The present work provides a new variational derivation of high-order PDE transforms. The fast Fourier transform is utilized to accomplish the PDE transform so as to avoid stringent stability constraints in solving high-order PDEs. As a consequence, the time integration of high-order PDEs can be done efficiently with the fast Fourier transform. The present approach is validated with a variety of test examples in two-dimensional and three-dimensional settings. We explore the impact of the PDE transform parameters, such as the PDE order and propagation time, on the quality of resulting surfaces. Additionally, we utilize a set of 10 proteins to compare the computational efficiency of the present surface generation method and a standard approach in Cartesian meshes. Moreover, we analyze the present method by examining some benchmark indicators of biomolecular surface, that is, surface area, surface-enclosed volume, solvation free energy, and surface electrostatic potential. A test set of 13 protein molecules is used in the present investigation. The electrostatic analysis is carried out via the Poisson-Boltzmann equation model. To further demonstrate the utility of the present PDE transform-based surface method, we solve the Poisson-Nernst-Planck equations with a PDE transform surface of a protein. Second-order convergence is observed for the electrostatic potential and concentrations. Finally, to test the capability and efficiency of the present PDE transform-based surface generation method, we apply it to the construction of an excessively large biomolecule, a

Studies of the charge instabilities in the complex nano-objects: clusters and bio-molecular systems

International Nuclear Information System (INIS)

Manil, B.

2007-11-01

For the last 6 years, my main research works focused on i) the Coulomb instabilities and the fragmentation processes of fullerenes and clusters of fullerenes ii) the stability and the reactivity of complex bio-molecular systems. Concerning the clusters of fullerenes, which are van der Waals type clusters, we have shown that the multiply charged species, obtained in collisions with slow highly charged ions, keep their structural properties but become very good electric conductor. In another hand, with the aim to understand the role of the biologic environment at the molecular scale in the irradiation damage of complex biomolecules, we have studied the charge stabilities of clusters of small biomolecules and the dissociation processes of larger nano-hydrated biomolecules. Theses studies have shown that first, specific molecular recognition mechanisms continue to exist in gas phase and secondly, a small and very simple biochemical environment is enough to change the dynamics of instabilities. (author)

DNA algorithms of implementing biomolecular databases on a biological computer.

Science.gov (United States)

Chang, Weng-Long; Vasilakos, Athanasios V

2015-01-01

In this paper, DNA algorithms are proposed to perform eight operations of relational algebra (calculus), which include Cartesian product, union, set difference, selection, projection, intersection, join, and division, on biomolecular relational databases.

The HADDOCK web server for data-driven biomolecular docking

NARCIS (Netherlands)

de Vries, S.J.|info:eu-repo/dai/nl/304837717; van Dijk, M.|info:eu-repo/dai/nl/325811113; Bonvin, A.M.J.J.|info:eu-repo/dai/nl/113691238

2010-01-01

Computational docking is the prediction or modeling of the three-dimensional structure of a biomolecular complex, starting from the structures of the individual molecules in their free, unbound form. HADDOC K is a popular docking program that takes a datadriven approach to docking, with support for

XML-based approaches for the integration of heterogeneous bio-molecular data.

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Mesiti, Marco; Jiménez-Ruiz, Ernesto; Sanz, Ismael; Berlanga-Llavori, Rafael; Perlasca, Paolo; Valentini, Giorgio; Manset, David

2009-10-15

The today's public database infrastructure spans a very large collection of heterogeneous biological data, opening new opportunities for molecular biology, bio-medical and bioinformatics research, but raising also new problems for their integration and computational processing. In this paper we survey the most interesting and novel approaches for the representation, integration and management of different kinds of biological data by exploiting XML and the related recommendations and approaches. Moreover, we present new and interesting cutting edge approaches for the appropriate management of heterogeneous biological data represented through XML. XML has succeeded in the integration of heterogeneous biomolecular information, and has established itself as the syntactic glue for biological data sources. Nevertheless, a large variety of XML-based data formats have been proposed, thus resulting in a difficult effective integration of bioinformatics data schemes. The adoption of a few semantic-rich standard formats is urgent to achieve a seamless integration of the current biological resources.

Scanning number and brightness yields absolute protein concentrations in live cells: a crucial parameter controlling functional bio-molecular interaction networks.

Science.gov (United States)

Papini, Christina; Royer, Catherine A

2018-02-01

Biological function results from properly timed bio-molecular interactions that transduce external or internal signals, resulting in any number of cellular fates, including triggering of cell-state transitions (division, differentiation, transformation, apoptosis), metabolic homeostasis and adjustment to changing physical or nutritional environments, amongst many more. These bio-molecular interactions can be modulated by chemical modifications of proteins, nucleic acids, lipids and other small molecules. They can result in bio-molecular transport from one cellular compartment to the other and often trigger specific enzyme activities involved in bio-molecular synthesis, modification or degradation. Clearly, a mechanistic understanding of any given high level biological function requires a quantitative characterization of the principal bio-molecular interactions involved and how these may change dynamically. Such information can be obtained using fluctation analysis, in particular scanning number and brightness, and used to build and test mechanistic models of the functional network to define which characteristics are the most important for its regulation.

GROMOS++Software for the Analysis of Biomolecular Simulation Trajectories

NARCIS (Netherlands)

Eichenberger, A.P.; Allison, J.R.; Dolenc, J.; Geerke, D.P.; Horta, B.A.C.; Meier, K; Oostenbrink, B.C.; Schmid, N.; Steiner, D; Wang, D.; van Gunsteren, W.F.

2011-01-01

GROMOS++ is a set of C++ programs for pre- and postprocessing of molecular dynamics simulation trajectories and as such is part of the GROningen MOlecular Simulation software for (bio)molecular simulation. It contains more than 70 programs that can be used to prepare data for the production of

Review of MEMS differential scanning calorimetry for biomolecular study

Science.gov (United States)

Yu, Shifeng; Wang, Shuyu; Lu, Ming; Zuo, Lei

2017-12-01

Differential scanning calorimetry (DSC) is one of the few techniques that allow direct determination of enthalpy values for binding reactions and conformational transitions in biomolecules. It provides the thermodynamics information of the biomolecules which consists of Gibbs free energy, enthalpy and entropy in a straightforward manner that enables deep understanding of the structure function relationship in biomolecules such as the folding/unfolding of protein and DNA, and ligand bindings. This review provides an up to date overview of the applications of DSC in biomolecular study such as the bovine serum albumin denaturation study, the relationship between the melting point of lysozyme and the scanning rate. We also introduce the recent advances of the development of micro-electro-mechanic-system (MEMS) based DSCs.

Integrated Spintronic Platforms for Biomolecular Recognition Detection

Science.gov (United States)

Martins, V. C.; Cardoso, F. A.; Loureiro, J.; Mercier, M.; Germano, J.; Cardoso, S.; Ferreira, R.; Fonseca, L. P.; Sousa, L.; Piedade, M. S.; Freitas, P. P.

2008-06-01

This paper covers recent developments in magnetoresistive based biochip platforms fabricated at INESC-MN, and their application to the detection and quantification of pathogenic waterborn microorganisms in water samples for human consumption. Such platforms are intended to give response to the increasing concern related to microbial contaminated water sources. The presented results concern the development of biological active DNA chips and protein chips and the demonstration of the detection capability of the present platforms. Two platforms are described, one including spintronic sensors only (spin-valve based or magnetic tunnel junction based), and the other, a fully scalable platform where each probe site consists of a MTJ in series with a thin film diode (TFD). Two microfluidic systems are described, for cell separation and concentration, and finally, the read out and control integrated electronics are described, allowing the realization of bioassays with a portable point of care unit. The present platforms already allow the detection of complementary biomolecular target recognition with 1 pM concentration.

Physics at the biomolecular interface fundamentals for molecular targeted therapy

CERN Document Server

Fernández, Ariel

2016-01-01

This book focuses primarily on the role of interfacial forces in understanding biological phenomena at the molecular scale. By providing a suitable statistical mechanical apparatus to handle the biomolecular interface, the book becomes uniquely positioned to address core problems in molecular biophysics. It highlights the importance of interfacial tension in delineating a solution to the protein folding problem, in unravelling the physico-chemical basis of enzyme catalysis and protein associations, and in rationally designing molecular targeted therapies. Thus grounded in fundamental science, the book develops a powerful technological platform for drug discovery, while it is set to inspire scientists at any level in their careers determined to address the major challenges in molecular biophysics. The acknowledgment of how exquisitely the structure and dynamics of proteins and their aqueous environment are related attests to the overdue recognition that biomolecular phenomena cannot be effectively understood w...

PREFACE: 1st Nano-IBCT Conference 2011 - Radiation Damage of Biomolecular Systems: Nanoscale Insights into Ion Beam Cancer Therapy

Science.gov (United States)

Huber, Bernd A.; Malot, Christiane; Domaracka, Alicja; Solov'yov, Andrey V.

2012-07-01

The 1st Nano-IBCT Conference entitled 'Radiation Damage in Biomolecular Systems: Nanoscale Insights into Ion Beam Cancer Therapy' was held in Caen, France, in October 2011. The Meeting was organised in the framework of the COST Action MP1002 (Nano-IBCT) which was launched in December 2010 (http://fias.uni-frankfurt.de/nano-ibct). This action aims to promote the understanding of mechanisms and processes underlying the radiation damage of biomolecular systems at the molecular and nanoscopic level and to use the findings to improve the strategy of Ion Beam Cancer Therapy. In the hope of achieving this, participants from different disciplines were invited to represent the fields of physics, biology, medicine and chemistry, and also included those from industry and the operators of hadron therapy centres. Ion beam therapy offers the possibility of excellent dose localization for treatment of malignant tumours, minimizing radiation damage in normal healthy tissue, while maximizing cell killing within the tumour. Several ion beam cancer therapy clinical centres are now operating in Europe and elsewhere. However, the full potential of such therapy can only be exploited by better understanding the physical, chemical and biological mechanisms that lead to cell death under ion irradiation. Considering a range of spatio-temporal scales, the proposed action therefore aims to combine the unique experimental and theoretical expertise available within Europe to acquire greater insight at the nanoscopic and molecular level into radiation damage induced by ion impact. Success in this endeavour will be both an important scientific breakthrough and give great impetus to the practical improvement of this innovative therapeutic technique. Ion therapy potentially provides an important advance in cancer therapy and the COST action MP1002 will be very significant in ensuring Europe's leadership in this field, providing the scientific background, required data and mechanistic insight which

An Overview of Biomolecular Event Extraction from Scientific Documents.

Science.gov (United States)

Vanegas, Jorge A; Matos, Sérgio; González, Fabio; Oliveira, José L

2015-01-01

This paper presents a review of state-of-the-art approaches to automatic extraction of biomolecular events from scientific texts. Events involving biomolecules such as genes, transcription factors, or enzymes, for example, have a central role in biological processes and functions and provide valuable information for describing physiological and pathogenesis mechanisms. Event extraction from biomedical literature has a broad range of applications, including support for information retrieval, knowledge summarization, and information extraction and discovery. However, automatic event extraction is a challenging task due to the ambiguity and diversity of natural language and higher-level linguistic phenomena, such as speculations and negations, which occur in biological texts and can lead to misunderstanding or incorrect interpretation. Many strategies have been proposed in the last decade, originating from different research areas such as natural language processing, machine learning, and statistics. This review summarizes the most representative approaches in biomolecular event extraction and presents an analysis of the current state of the art and of commonly used methods, features, and tools. Finally, current research trends and future perspectives are also discussed.

An Overview of Biomolecular Event Extraction from Scientific Documents

Directory of Open Access Journals (Sweden)

Jorge A. Vanegas

2015-01-01

Full Text Available This paper presents a review of state-of-the-art approaches to automatic extraction of biomolecular events from scientific texts. Events involving biomolecules such as genes, transcription factors, or enzymes, for example, have a central role in biological processes and functions and provide valuable information for describing physiological and pathogenesis mechanisms. Event extraction from biomedical literature has a broad range of applications, including support for information retrieval, knowledge summarization, and information extraction and discovery. However, automatic event extraction is a challenging task due to the ambiguity and diversity of natural language and higher-level linguistic phenomena, such as speculations and negations, which occur in biological texts and can lead to misunderstanding or incorrect interpretation. Many strategies have been proposed in the last decade, originating from different research areas such as natural language processing, machine learning, and statistics. This review summarizes the most representative approaches in biomolecular event extraction and presents an analysis of the current state of the art and of commonly used methods, features, and tools. Finally, current research trends and future perspectives are also discussed.

Photochirogenesis: Photochemical Models on the Origin of Biomolecular Homochirality

Directory of Open Access Journals (Sweden)

Cornelia Meinert

2010-05-01

Full Text Available Current research focuses on a better understanding of the origin of biomolecular asymmetry by the identification and detection of the possibly first chiral molecules that were involved in the appearance and evolution of life on Earth. We have reasons to assume that these molecules were specific chiral amino acids. Chiral amino acids have been identified in both chondritic meteorites and simulated interstellar ices. Present research reasons that circularly polarized electromagnetic radiation was identified in interstellar environments and an asymmetric interstellar photon-molecule interaction might have triggered biomolecular symmetry breaking. We review on the possible prebiotic interaction of ‘chiral photons’ in the form of circularly polarized light, with early chiral organic molecules. We will highlight recent studies on enantioselective photolysis of racemic amino acids by circularly polarized light and experiments on the asymmetric photochemical synthesis of amino acids from only one C and one N containing molecules by simulating interstellar environments. Both approaches are based on circular dichroic transitions of amino acids that will be presented as well.

A hydrogel-based versatile screening platform for specific biomolecular recognition in a well plate format.

Science.gov (United States)

Beer, Meike V; Rech, Claudia; Diederichs, Sylvia; Hahn, Kathrin; Bruellhoff, Kristina; Möller, Martin; Elling, Lothar; Groll, Jürgen

2012-04-01

Precise determination of biomolecular interactions in high throughput crucially depends on a surface coating technique that allows immobilization of a variety of interaction partners in a non-interacting environment. We present a one-step hydrogel coating system based on isocyanate functional six-arm poly(ethylene oxide)-based star polymers for commercially available 96-well microtiter plates that combines a straightforward and robust coating application with versatile bio-functionalization. This system generates resistance to unspecific protein adsorption and cell adhesion, as demonstrated with fluorescently labeled bovine serum albumin and primary human dermal fibroblasts (HDF), and high specificity for the assessment of biomolecular recognition processes when ligands are immobilized on this surface. One particular advantage is the wide range of biomolecules that can be immobilized and convert the per se inert coating into a specifically interacting surface. We here demonstrate the immobilization and quantification of a broad range of biochemically important ligands, such as peptide sequences GRGDS and GRGDSK-biotin, the broadly applicable coupler molecule biocytin, the protein fibronectin, and the carbohydrates N-acetylglucosamine and N-acetyllactosamine. A simplified protocol for an enzyme-linked immunosorbent assay was established for the detection and quantification of ligands on the coating surface. Cell adhesion on the peptide and protein-modified surfaces was assessed using HDF. All coatings were applied using a one-step preparation technique, including bioactivation, which makes the system suitable for high-throughput screening in a format that is compatible with the most routinely used testing systems.

Changes in biomolecular profile in a single nucleolus during cell fixation.

Science.gov (United States)

Kuzmin, Andrey N; Pliss, Artem; Prasad, Paras N

2014-11-04

Fixation of biological sample is an essential technique applied in order to "freeze" in time the intracellular molecular content. However, fixation induces changes of the cellular molecular structure, which mask physiological distribution of biomolecules and bias interpretation of results. Accurate, sensitive, and comprehensive characterization of changes in biomolecular composition, occurring during fixation, is crucial for proper analysis of experimental data. Here we apply biomolecular component analysis for Raman spectra measured in the same nucleoli of HeLa cells before and after fixation by either formaldehyde solution or by chilled ethanol. It is found that fixation in formaldehyde does not strongly affect the Raman spectra of nucleolar biomolecular components, but may significantly decrease the nucleolar RNA concentration. At the same time, ethanol fixation leads to a proportional increase (up to 40%) in concentrations of nucleolar proteins and RNA, most likely due to cell shrinkage occurring in the presence of coagulant fixative. Ethanol fixation also triggers changes in composition of nucleolar proteome, as indicated by an overall reduction of the α-helical structure of proteins and increase in the concentration of proteins containing the β-sheet conformation. We conclude that cross-linking fixation is a more appropriate protocol for mapping of proteins in situ. At the same time, ethanol fixation is preferential for studies of RNA-containing macromolecules. We supplemented our quantitative Raman spectroscopic measurements with mapping of the protein and lipid macromolecular groups in live and fixed cells using coherent anti-Stokes Raman scattering nonlinear optical imaging.

Affinity Capillary Electrophoresis – A Powerful Tool to Investigate Biomolecular Interactions

Czech Academy of Sciences Publication Activity Database

Kašička, Václav

2017-01-01

Roč. 30, č. 5 (2017), s. 248 ISSN 1471-6577 Institutional support: RVO:61388963 Keywords : capillary affinity electrophoresis * biomolecular interactions * binding constants Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 0.663, year: 2016

Developing the Biomolecular Screening Facility at the EPFL into the Chemical Biology Screening Platform for Switzerland.

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Turcatti, Gerardo

2014-05-01

The Biomolecular Screening Facility (BSF) is a multidisciplinary laboratory created in 2006 at the Ecole Polytechnique Federale de Lausanne (EPFL) to perform medium and high throughput screening in life sciences-related projects. The BSF was conceived and developed to meet the needs of a wide range of researchers, without privileging a particular biological discipline or therapeutic area. The facility has the necessary infrastructure, multidisciplinary expertise and flexibility to perform large screening programs using small interfering RNAs (siRNAs) and chemical collections in the areas of chemical biology, systems biology and drug discovery. In the framework of the National Centres of Competence in Research (NCCR) Chemical Biology, the BSF is hosting 'ACCESS', the Academic Chemical Screening Platform of Switzerland that provides the scientific community with chemical diversity, screening facilities and know-how in chemical genetics. In addition, the BSF started its own applied research axes that are driven by innovation in thematic areas related to preclinical drug discovery and discovery of bioactive probes.

Integration of biomolecular logic gates with field-effect transducers

Energy Technology Data Exchange (ETDEWEB)

Poghossian, A., E-mail: a.poghossian@fz-juelich.de [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Institute of Bio- and Nanosystems, Research Centre Juelich GmbH, D-52425 Juelich (Germany); Malzahn, K. [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Abouzar, M.H. [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Institute of Bio- and Nanosystems, Research Centre Juelich GmbH, D-52425 Juelich (Germany); Mehndiratta, P. [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Katz, E. [Department of Chemistry and Biomolecular Science, NanoBio Laboratory (NABLAB), Clarkson University, Potsdam, NY 13699-5810 (United States); Schoening, M.J. [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Institute of Bio- and Nanosystems, Research Centre Juelich GmbH, D-52425 Juelich (Germany)

2011-11-01

Highlights: > Enzyme-based AND/OR logic gates are integrated with a capacitive field-effect sensor. > The AND/OR logic gates compose of multi-enzyme system immobilised on sensor surface. > Logic gates were activated by different combinations of chemical inputs (analytes). > The logic output (pH change) produced by the enzymes was read out by the sensor. - Abstract: The integration of biomolecular logic gates with field-effect devices - the basic element of conventional electronic logic gates and computing - is one of the most attractive and promising approaches for the transformation of biomolecular logic principles into macroscopically useable electrical output signals. In this work, capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensors based on a p-Si-SiO{sub 2}-Ta{sub 2}O{sub 5} structure modified with a multi-enzyme membrane have been used for electronic transduction of biochemical signals processed by enzyme-based OR and AND logic gates. The realised OR logic gate composes of two enzymes (glucose oxidase and esterase) and was activated by ethyl butyrate or/and glucose. The AND logic gate composes of three enzymes (invertase, mutarotase and glucose oxidase) and was activated by two chemical input signals: sucrose and dissolved oxygen. The developed integrated enzyme logic gates produce local pH changes at the EIS sensor surface as a result of biochemical reactions activated by different combinations of chemical input signals, while the pH value of the bulk solution remains unchanged. The pH-induced charge changes at the gate-insulator (Ta{sub 2}O{sub 5}) surface of the EIS transducer result in an electronic signal corresponding to the logic output produced by the immobilised enzymes. The logic output signals have been read out by means of a constant-capacitance method.

Integration of biomolecular logic gates with field-effect transducers

International Nuclear Information System (INIS)

Poghossian, A.; Malzahn, K.; Abouzar, M.H.; Mehndiratta, P.; Katz, E.; Schoening, M.J.

2011-01-01

Highlights: → Enzyme-based AND/OR logic gates are integrated with a capacitive field-effect sensor. → The AND/OR logic gates compose of multi-enzyme system immobilised on sensor surface. → Logic gates were activated by different combinations of chemical inputs (analytes). → The logic output (pH change) produced by the enzymes was read out by the sensor. - Abstract: The integration of biomolecular logic gates with field-effect devices - the basic element of conventional electronic logic gates and computing - is one of the most attractive and promising approaches for the transformation of biomolecular logic principles into macroscopically useable electrical output signals. In this work, capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensors based on a p-Si-SiO 2 -Ta 2 O 5 structure modified with a multi-enzyme membrane have been used for electronic transduction of biochemical signals processed by enzyme-based OR and AND logic gates. The realised OR logic gate composes of two enzymes (glucose oxidase and esterase) and was activated by ethyl butyrate or/and glucose. The AND logic gate composes of three enzymes (invertase, mutarotase and glucose oxidase) and was activated by two chemical input signals: sucrose and dissolved oxygen. The developed integrated enzyme logic gates produce local pH changes at the EIS sensor surface as a result of biochemical reactions activated by different combinations of chemical input signals, while the pH value of the bulk solution remains unchanged. The pH-induced charge changes at the gate-insulator (Ta 2 O 5 ) surface of the EIS transducer result in an electronic signal corresponding to the logic output produced by the immobilised enzymes. The logic output signals have been read out by means of a constant-capacitance method.

Overcoming the solubility limit with solubility-enhancement tags: successful applications in biomolecular NMR studies

International Nuclear Information System (INIS)

Zhou Pei; Wagner, Gerhard

2010-01-01

Although the rapid progress of NMR technology has significantly expanded the range of NMR-trackable systems, preparation of NMR-suitable samples that are highly soluble and stable remains a bottleneck for studies of many biological systems. The application of solubility-enhancement tags (SETs) has been highly effective in overcoming solubility and sample stability issues and has enabled structural studies of important biological systems previously deemed unapproachable by solution NMR techniques. In this review, we provide a brief survey of the development and successful applications of the SET strategy in biomolecular NMR. We also comment on the criteria for choosing optimal SETs, such as for differently charged target proteins, and recent new developments on NMR-invisible SETs.

Computer Programming and Biomolecular Structure Studies: A Step beyond Internet Bioinformatics

Science.gov (United States)

Likic, Vladimir A.

2006-01-01

This article describes the experience of teaching structural bioinformatics to third year undergraduate students in a subject titled "Biomolecular Structure and Bioinformatics." Students were introduced to computer programming and used this knowledge in a practical application as an alternative to the well established Internet bioinformatics…

Multiresolution persistent homology for excessively large biomolecular datasets

Energy Technology Data Exchange (ETDEWEB)

Xia, Kelin; Zhao, Zhixiong [Department of Mathematics, Michigan State University, East Lansing, Michigan 48824 (United States); Wei, Guo-Wei, E-mail: wei@math.msu.edu [Department of Mathematics, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824 (United States)

2015-10-07

Although persistent homology has emerged as a promising tool for the topological simplification of complex data, it is computationally intractable for large datasets. We introduce multiresolution persistent homology to handle excessively large datasets. We match the resolution with the scale of interest so as to represent large scale datasets with appropriate resolution. We utilize flexibility-rigidity index to access the topological connectivity of the data set and define a rigidity density for the filtration analysis. By appropriately tuning the resolution of the rigidity density, we are able to focus the topological lens on the scale of interest. The proposed multiresolution topological analysis is validated by a hexagonal fractal image which has three distinct scales. We further demonstrate the proposed method for extracting topological fingerprints from DNA molecules. In particular, the topological persistence of a virus capsid with 273 780 atoms is successfully analyzed which would otherwise be inaccessible to the normal point cloud method and unreliable by using coarse-grained multiscale persistent homology. The proposed method has also been successfully applied to the protein domain classification, which is the first time that persistent homology is used for practical protein domain analysis, to our knowledge. The proposed multiresolution topological method has potential applications in arbitrary data sets, such as social networks, biological networks, and graphs.

Scanning probe and optical tweezer investigations of biomolecular interactions

International Nuclear Information System (INIS)

Rigby-Singleton, Shellie

2002-01-01

A complex array of intermolecular forces controls the interactions between and within biological molecules. The desire to empirically explore the fundamental forces has led to the development of several biophysical techniques. Of these, the atomic force microscope (AFM) and the optical tweezers have been employed throughout this thesis to monitor the intermolecular forces involved in biomolecular interactions. The AFM is a well-established force sensing technique capable of measuring biomolecular interactions at a single molecule level. However, its versatility has not been extrapolated to the investigation of a drug-enzyme complex. The energy landscape for the force induced dissociation of the DHFR-methotrexate complex was studied. Revealing an energy barrier to dissociation located ∼0.3 nm from the bound state. Unfortunately, the AFM has a limited range of accessible loading rates and in order to profile the complete energy landscape alternative force sensing instrumentation should be considered, for example the BFP and optical tweezers. Thus, this thesis outlines the development and construction an optical trap capable of measuring intermolecular forces between biomolecules at the single molecule level. To demonstrate the force sensing abilities of the optical set up, proof of principle measurements were performed which investigate the interactions between proteins and polymer surfaces subjected to varying degrees of argon plasma treatment. Complementary data was gained from measurements performed independently by the AFM. Changes in polymer resistance to proteins as a response to changes in polymer surface chemistry were detected utilising both AFM and optical tweezers measurements. Finally, the AFM and optical tweezers were employed as ultrasensitive biosensors. Single molecule investigations of the antibody-antigen interaction between the cardiac troponin I marker and its complementary antibody, reveals the impact therapeutic concentrations of heparin have

The use of gold nanoparticle aggregation for DNA computing and logic-based biomolecular detection

International Nuclear Information System (INIS)

Lee, In-Hee; Yang, Kyung-Ae; Zhang, Byoung-Tak; Lee, Ji-Hoon; Park, Ji-Yoon; Chai, Young Gyu; Lee, Jae-Hoon

2008-01-01

The use of DNA molecules as a physical computational material has attracted much interest, especially in the area of DNA computing. DNAs are also useful for logical control and analysis of biological systems if efficient visualization methods are available. Here we present a quick and simple visualization technique that displays the results of the DNA computing process based on a colorimetric change induced by gold nanoparticle aggregation, and we apply it to the logic-based detection of biomolecules. Our results demonstrate its effectiveness in both DNA-based logical computation and logic-based biomolecular detection

AIM for Allostery: Using the Ising Model to Understand Information Processing and Transmission in Allosteric Biomolecular Systems.

Science.gov (United States)

LeVine, Michael V; Weinstein, Harel

2015-05-01

In performing their biological functions, molecular machines must process and transmit information with high fidelity. Information transmission requires dynamic coupling between the conformations of discrete structural components within the protein positioned far from one another on the molecular scale. This type of biomolecular "action at a distance" is termed allostery . Although allostery is ubiquitous in biological regulation and signal transduction, its treatment in theoretical models has mostly eschewed quantitative descriptions involving the system's underlying structural components and their interactions. Here, we show how Ising models can be used to formulate an approach to allostery in a structural context of interactions between the constitutive components by building simple allosteric constructs we termed Allosteric Ising Models (AIMs). We introduce the use of AIMs in analytical and numerical calculations that relate thermodynamic descriptions of allostery to the structural context, and then show that many fundamental properties of allostery, such as the multiplicative property of parallel allosteric channels, are revealed from the analysis of such models. The power of exploring mechanistic structural models of allosteric function in more complex systems by using AIMs is demonstrated by building a model of allosteric signaling for an experimentally well-characterized asymmetric homodimer of the dopamine D2 receptor.

Poisson-Nernst-Planck Equations for Simulating Biomolecular Diffusion-Reaction Processes I: Finite Element Solutions.

Science.gov (United States)

Lu, Benzhuo; Holst, Michael J; McCammon, J Andrew; Zhou, Y C

2010-09-20

In this paper we developed accurate finite element methods for solving 3-D Poisson-Nernst-Planck (PNP) equations with singular permanent charges for electrodiffusion in solvated biomolecular systems. The electrostatic Poisson equation was defined in the biomolecules and in the solvent, while the Nernst-Planck equation was defined only in the solvent. We applied a stable regularization scheme to remove the singular component of the electrostatic potential induced by the permanent charges inside biomolecules, and formulated regular, well-posed PNP equations. An inexact-Newton method was used to solve the coupled nonlinear elliptic equations for the steady problems; while an Adams-Bashforth-Crank-Nicolson method was devised for time integration for the unsteady electrodiffusion. We numerically investigated the conditioning of the stiffness matrices for the finite element approximations of the two formulations of the Nernst-Planck equation, and theoretically proved that the transformed formulation is always associated with an ill-conditioned stiffness matrix. We also studied the electroneutrality of the solution and its relation with the boundary conditions on the molecular surface, and concluded that a large net charge concentration is always present near the molecular surface due to the presence of multiple species of charged particles in the solution. The numerical methods are shown to be accurate and stable by various test problems, and are applicable to real large-scale biophysical electrodiffusion problems.

Synergy of Two Highly Specific Biomolecular Recognition Events

DEFF Research Database (Denmark)

Ejlersen, Maria; Christensen, Niels Johan; Sørensen, Kasper K

2018-01-01

Two highly specific biomolecular recognition events, nucleic acid duplex hybridization and DNA-peptide recognition in the minor groove, were coalesced in a miniature ensemble for the first time by covalently attaching a natural AT-hook peptide motif to nucleic acid duplexes via a 2'-amino......-LNA scaffold. A combination of molecular dynamics simulations and ultraviolet thermal denaturation studies revealed high sequence-specific affinity of the peptide-oligonucleotide conjugates (POCs) when binding to complementary DNA strands, leveraging the bioinformation encrypted in the minor groove of DNA...

Biomolecular ions in superfluid helium nanodroplets

Energy Technology Data Exchange (ETDEWEB)

Gonzalez Florez, Ana Isabel

2016-07-01

The function of a biological molecule is closely related to its structure. As a result, understanding and predicting biomolecular structure has become the focus of an extensive field of research. However, the investigation of molecular structure can be hampered by two main difficulties: the inherent complications that may arise from studying biological molecules in their native environment, and the potential congestion of the experimental results as a consequence of the large number of degrees of freedom present in these molecules. In this work, a new experimental setup has been developed and established in order to overcome the afore mentioned limitations combining structure-sensitive gas-phase methods with superfluid helium droplets. First, biological molecules are ionised and brought into the gas phase, often referred to as a clean-room environment, where the species of interest are isolated from their surroundings and, thus, intermolecular interactions are absent. The mass-to-charge selected biomolecules are then embedded inside clusters of superfluid helium with an equilibrium temperature of ∝0.37 K. As a result, the internal energy of the molecules is lowered, thereby reducing the number of populated quantum states. Finally, the local hydrogen bonding patterns of the molecules are investigated by probing specific vibrational modes using the Fritz Haber Institute's free electron laser as a source of infrared radiation. Although the structure of a wide variety of molecules has been studied making use of the sub-Kelvin environment provided by superfluid helium droplets, the suitability of this method for the investigation of biological molecular ions was still unclear. However, the experimental results presented in this thesis demonstrate the applicability of this experimental approach in order to study the structure of intact, large biomolecular ions and the first vibrational spectrum of the protonated pentapeptide leu-enkephalin embedded in helium

Biomolecular ions in superfluid helium nanodroplets

International Nuclear Information System (INIS)

Gonzalez Florez, Ana Isabel

2016-01-01

The function of a biological molecule is closely related to its structure. As a result, understanding and predicting biomolecular structure has become the focus of an extensive field of research. However, the investigation of molecular structure can be hampered by two main difficulties: the inherent complications that may arise from studying biological molecules in their native environment, and the potential congestion of the experimental results as a consequence of the large number of degrees of freedom present in these molecules. In this work, a new experimental setup has been developed and established in order to overcome the afore mentioned limitations combining structure-sensitive gas-phase methods with superfluid helium droplets. First, biological molecules are ionised and brought into the gas phase, often referred to as a clean-room environment, where the species of interest are isolated from their surroundings and, thus, intermolecular interactions are absent. The mass-to-charge selected biomolecules are then embedded inside clusters of superfluid helium with an equilibrium temperature of ∝0.37 K. As a result, the internal energy of the molecules is lowered, thereby reducing the number of populated quantum states. Finally, the local hydrogen bonding patterns of the molecules are investigated by probing specific vibrational modes using the Fritz Haber Institute's free electron laser as a source of infrared radiation. Although the structure of a wide variety of molecules has been studied making use of the sub-Kelvin environment provided by superfluid helium droplets, the suitability of this method for the investigation of biological molecular ions was still unclear. However, the experimental results presented in this thesis demonstrate the applicability of this experimental approach in order to study the structure of intact, large biomolecular ions and the first vibrational spectrum of the protonated pentapeptide leu-enkephalin embedded in helium

Biomolecular solid state NMR with magic-angle spinning at 25K.

Science.gov (United States)

Thurber, Kent R; Tycko, Robert

2008-12-01

A magic-angle spinning (MAS) probe has been constructed which allows the sample to be cooled with helium, while the MAS bearing and drive gases are nitrogen. The sample can be cooled to 25K using roughly 3 L/h of liquid helium, while the 4-mm diameter rotor spins at 6.7 kHz with good stability (+/-5 Hz) for many hours. Proton decoupling fields up to at least 130 kHz can be applied. This helium-cooled MAS probe enables a variety of one-dimensional and two-dimensional NMR experiments on biomolecular solids and other materials at low temperatures, with signal-to-noise proportional to 1/T. We show examples of low-temperature (13)C NMR data for two biomolecular samples, namely the peptide Abeta(14-23) in the form of amyloid fibrils and the protein HP35 in frozen glycerol/water solution. Issues related to temperature calibration, spin-lattice relaxation at low temperatures, paramagnetic doping of frozen solutions, and (13)C MAS NMR linewidths are discussed.

Investigating biomolecular recognition at the cell surface using atomic force microscopy.

Science.gov (United States)

Wang, Congzhou; Yadavalli, Vamsi K

2014-05-01

Probing the interaction forces that drive biomolecular recognition on cell surfaces is essential for understanding diverse biological processes. Force spectroscopy has been a widely used dynamic analytical technique, allowing measurement of such interactions at the molecular and cellular level. The capabilities of working under near physiological environments, combined with excellent force and lateral resolution make atomic force microscopy (AFM)-based force spectroscopy a powerful approach to measure biomolecular interaction forces not only on non-biological substrates, but also on soft, dynamic cell surfaces. Over the last few years, AFM-based force spectroscopy has provided biophysical insight into how biomolecules on cell surfaces interact with each other and induce relevant biological processes. In this review, we focus on describing the technique of force spectroscopy using the AFM, specifically in the context of probing cell surfaces. We summarize recent progress in understanding the recognition and interactions between macromolecules that may be found at cell surfaces from a force spectroscopy perspective. We further discuss the challenges and future prospects of the application of this versatile technique. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cancer genetics meets biomolecular mechanism-bridging an age-old gulf.

Science.gov (United States)

González-Sánchez, Juan Carlos; Raimondi, Francesco; Russell, Robert B

2018-02-01

Increasingly available genomic sequencing data are exploited to identify genes and variants contributing to diseases, particularly cancer. Traditionally, methods to find such variants have relied heavily on allele frequency and/or familial history, often neglecting to consider any mechanistic understanding of their functional consequences. Thus, while the set of known cancer-related genes has increased, for many, their mechanistic role in the disease is not completely understood. This issue highlights a wide gap between the disciplines of genetics, which largely aims to correlate genetic events with phenotype, and molecular biology, which ultimately aims at a mechanistic understanding of biological processes. Fortunately, new methods and several systematic studies have proved illuminating for many disease genes and variants by integrating sequencing with mechanistic data, including biomolecular structures and interactions. These have provided new interpretations for known mutations and suggested new disease-relevant variants and genes. Here, we review these approaches and discuss particular examples where these have had a profound impact on the understanding of human cancers. © 2018 Federation of European Biochemical Societies.

Multiscale Persistent Functions for Biomolecular Structure Characterization

Energy Technology Data Exchange (ETDEWEB)

Xia, Kelin [Nanyang Technological University (Singapore). Division of Mathematical Sciences, School of Physical, Mathematical Sciences and School of Biological Sciences; Li, Zhiming [Central China Normal University, Wuhan (China). Key Laboratory of Quark and Lepton Physics (MOE) and Institute of Particle Physics; Mu, Lin [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Computer Science and Mathematics Division

2017-11-02

Here in this paper, we introduce multiscale persistent functions for biomolecular structure characterization. The essential idea is to combine our multiscale rigidity functions (MRFs) with persistent homology analysis, so as to construct a series of multiscale persistent functions, particularly multiscale persistent entropies, for structure characterization. To clarify the fundamental idea of our method, the multiscale persistent entropy (MPE) model is discussed in great detail. Mathematically, unlike the previous persistent entropy (Chintakunta et al. in Pattern Recognit 48(2):391–401, 2015; Merelli et al. in Entropy 17(10):6872–6892, 2015; Rucco et al. in: Proceedings of ECCS 2014, Springer, pp 117–128, 2016), a special resolution parameter is incorporated into our model. Various scales can be achieved by tuning its value. Physically, our MPE can be used in conformational entropy evaluation. More specifically, it is found that our method incorporates in it a natural classification scheme. This is achieved through a density filtration of an MRF built from angular distributions. To further validate our model, a systematical comparison with the traditional entropy evaluation model is done. Additionally, it is found that our model is able to preserve the intrinsic topological features of biomolecular data much better than traditional approaches, particularly for resolutions in the intermediate range. Moreover, by comparing with traditional entropies from various grid sizes, bond angle-based methods and a persistent homology-based support vector machine method (Cang et al. in Mol Based Math Biol 3:140–162, 2015), we find that our MPE method gives the best results in terms of average true positive rate in a classic protein structure classification test. More interestingly, all-alpha and all-beta protein classes can be clearly separated from each other with zero error only in our model. Finally, a special protein structure index (PSI) is proposed, for the first

Integrative NMR for biomolecular research

International Nuclear Information System (INIS)

Lee, Woonghee; Cornilescu, Gabriel; Dashti, Hesam; Eghbalnia, Hamid R.; Tonelli, Marco; Westler, William M.; Butcher, Samuel E.; Henzler-Wildman, Katherine A.; Markley, John L.

2016-01-01

NMR spectroscopy is a powerful technique for determining structural and functional features of biomolecules in physiological solution as well as for observing their intermolecular interactions in real-time. However, complex steps associated with its practice have made the approach daunting for non-specialists. We introduce an NMR platform that makes biomolecular NMR spectroscopy much more accessible by integrating tools, databases, web services, and video tutorials that can be launched by simple installation of NMRFAM software packages or using a cross-platform virtual machine that can be run on any standard laptop or desktop computer. The software package can be downloaded freely from the NMRFAM software download page ( http://pine.nmrfam.wisc.edu/download-packages.html http://pine.nmrfam.wisc.edu/download_packages.html ), and detailed instructions are available from the Integrative NMR Video Tutorial page ( http://pine.nmrfam.wisc.edu/integrative.html http://pine.nmrfam.wisc.edu/integrative.html ).

Integrative NMR for biomolecular research

Energy Technology Data Exchange (ETDEWEB)

Lee, Woonghee, E-mail: whlee@nmrfam.wisc.edu; Cornilescu, Gabriel; Dashti, Hesam; Eghbalnia, Hamid R.; Tonelli, Marco; Westler, William M.; Butcher, Samuel E.; Henzler-Wildman, Katherine A.; Markley, John L., E-mail: markley@nmrfam.wisc.edu [University of Wisconsin-Madison, National Magnetic Resonance Facility at Madison and Biochemistry Department (United States)

2016-04-15

NMR spectroscopy is a powerful technique for determining structural and functional features of biomolecules in physiological solution as well as for observing their intermolecular interactions in real-time. However, complex steps associated with its practice have made the approach daunting for non-specialists. We introduce an NMR platform that makes biomolecular NMR spectroscopy much more accessible by integrating tools, databases, web services, and video tutorials that can be launched by simple installation of NMRFAM software packages or using a cross-platform virtual machine that can be run on any standard laptop or desktop computer. The software package can be downloaded freely from the NMRFAM software download page ( http://pine.nmrfam.wisc.edu/download-packages.html http://pine.nmrfam.wisc.edu/download{sub p}ackages.html ), and detailed instructions are available from the Integrative NMR Video Tutorial page ( http://pine.nmrfam.wisc.edu/integrative.html http://pine.nmrfam.wisc.edu/integrative.html ).

Sequence co-evolutionary information is a natural partner to minimally-frustrated models of biomolecular dynamics [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Jeffrey K Noel

2016-01-01

Full Text Available Experimentally derived structural constraints have been crucial to the implementation of computational models of biomolecular dynamics. For example, not only does crystallography provide essential starting points for molecular simulations but also high-resolution structures permit for parameterization of simplified models. Since the energy landscapes for proteins and other biomolecules have been shown to be minimally frustrated and therefore funneled, these structure-based models have played a major role in understanding the mechanisms governing folding and many functions of these systems. Structural information, however, may be limited in many interesting cases. Recently, the statistical analysis of residue co-evolution in families of protein sequences has provided a complementary method of discovering residue-residue contact interactions involved in functional configurations. These functional configurations are often transient and difficult to capture experimentally. Thus, co-evolutionary information can be merged with that available for experimentally characterized low free-energy structures, in order to more fully capture the true underlying biomolecular energy landscape.

Sop-GPU: accelerating biomolecular simulations in the centisecond timescale using graphics processors.

Science.gov (United States)

Zhmurov, A; Dima, R I; Kholodov, Y; Barsegov, V

2010-11-01

Theoretical exploration of fundamental biological processes involving the forced unraveling of multimeric proteins, the sliding motion in protein fibers and the mechanical deformation of biomolecular assemblies under physiological force loads is challenging even for distributed computing systems. Using a C(α)-based coarse-grained self organized polymer (SOP) model, we implemented the Langevin simulations of proteins on graphics processing units (SOP-GPU program). We assessed the computational performance of an end-to-end application of the program, where all the steps of the algorithm are running on a GPU, by profiling the simulation time and memory usage for a number of test systems. The ∼90-fold computational speedup on a GPU, compared with an optimized central processing unit program, enabled us to follow the dynamics in the centisecond timescale, and to obtain the force-extension profiles using experimental pulling speeds (v(f) = 1-10 μm/s) employed in atomic force microscopy and in optical tweezers-based dynamic force spectroscopy. We found that the mechanical molecular response critically depends on the conditions of force application and that the kinetics and pathways for unfolding change drastically even upon a modest 10-fold increase in v(f). This implies that, to resolve accurately the free energy landscape and to relate the results of single-molecule experiments in vitro and in silico, molecular simulations should be carried out under the experimentally relevant force loads. This can be accomplished in reasonable wall-clock time for biomolecules of size as large as 10(5) residues using the SOP-GPU package. © 2010 Wiley-Liss, Inc.

Versatile single-molecule multi-color excitation and detection fluorescence setup for studying biomolecular dynamics

KAUST Repository

Sobhy, M. A.; Elshenawy, M. M.; Takahashi, Masateru; Whitman, B. H.; Walter, N. G.; Hamdan, S. M.

2011-01-01

Single-molecule fluorescence imaging is at the forefront of tools applied to study biomolecular dynamics both in vitro and in vivo. The ability of the single-molecule fluorescence microscope to conduct simultaneous multi-color excitation

Electrostatics in biomolecular simulations : where are we now and where are we heading?

NARCIS (Netherlands)

Karttunen, M.E.J.; Rottler, J.; Vattulainen, I.; Sagui, C.

2008-01-01

Chapter 2. In this review, we discuss current methods and developments in the treatment of electrostatic interactions in biomolecular and soft matter simulations. We review the current ‘work horses’, namely, Ewald summation based methods such the Particle-Mesh Ewald, and others, and also newer

Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks

DEFF Research Database (Denmark)

Soberano de Oliveira, Ana Paula; Patil, Kiran Raosaheb; Nielsen, Jens

2008-01-01

is to use the topology of bio-molecular interaction networks in order to constrain the solution space. Such approaches systematically integrate the existing biological knowledge with the 'omics' data. Results: Here we introduce a hypothesis-driven method that integrates bio-molecular network topology......Background: Uncovering the operating principles underlying cellular processes by using 'omics' data is often a difficult task due to the high-dimensionality of the solution space that spans all interactions among the bio-molecules under consideration. A rational way to overcome this problem...... with transcriptome data, thereby allowing the identification of key biological features (Reporter Features) around which transcriptional changes are significantly concentrated. We have combined transcriptome data with different biological networks in order to identify Reporter Gene Ontologies, Reporter Transcription...

Design of an embedded inverse-feedforward biomolecular tracking controller for enzymatic reaction processes.

Science.gov (United States)

Foo, Mathias; Kim, Jongrae; Sawlekar, Rucha; Bates, Declan G

2017-04-06

Feedback control is widely used in chemical engineering to improve the performance and robustness of chemical processes. Feedback controllers require a 'subtractor' that is able to compute the error between the process output and the reference signal. In the case of embedded biomolecular control circuits, subtractors designed using standard chemical reaction network theory can only realise one-sided subtraction, rendering standard controller design approaches inadequate. Here, we show how a biomolecular controller that allows tracking of required changes in the outputs of enzymatic reaction processes can be designed and implemented within the framework of chemical reaction network theory. The controller architecture employs an inversion-based feedforward controller that compensates for the limitations of the one-sided subtractor that generates the error signals for a feedback controller. The proposed approach requires significantly fewer chemical reactions to implement than alternative designs, and should have wide applicability throughout the fields of synthetic biology and biological engineering.

Applications of atomic force microscopy to the studies of biomaterials in biomolecular systems

Science.gov (United States)

Ma, Xiang

Atomic force microscopy (AFM) is a unique tool for the studies of nanoscale structures and interactions. In this dissertation, I applied AFM to study transitions among multiple states of biomaterials in three different microscopic biomolecular systems: MukB-dependent DNA condensation, holdfast adhesion, and virus elasticity. To elucidate the mechanism of MukB-dependent DNA condensation, I have studied the conformational changes of MukB proteins as indicators for the strength of interactions between MukB, DNA and other molecular factors, such as magnesium and ParC proteins, using high-resolution AFM imaging. To determine the physical origins of holdfast adhesion, I have investigated the dynamics of adhesive force development of the holdfast, employing AFM force spectroscopy. By measuring rupture forces between the holdfast and the substrate, I showed that the holdfast adhesion is strongly time-dependent and involves transformations at multiple time scales. Understanding the mechanisms of adhesion force development of the holdfast will be critical for future engineering of holdfasts properties for various applications. Finally, I have examined the elasticity of self-assembled hepatitis B virus-like particles (HBV VLPs) and brome mosaic virus (BMV) in response to changes of pH and salinity, using AFM nanoindentation. The distributions of elasticity were mapped on a single particle level and compared between empty, RNA- and gold-filled HBV VLPs. I found that a single HBV VLP showed heterogeneous distribution of elasticity and a two-step buckling transition, suggesting a discrete property of HBV capsids. For BMV, I have showed that viruses containing different RNA molecules can be distinguished by mechanical measurements, while they are indistinguishable by morphology. I also studied the effect of pH on the elastic behaviors of three-particle BMV and R3/4 BMV. This study can yield insights into RNA presentation/release mechanisms, and could help us to design novel drug

Instrumental biosensors: new perspectives for the analysis of biomolecular interactions.

Science.gov (United States)

Nice, E C; Catimel, B

1999-04-01

The use of instrumental biosensors in basic research to measure biomolecular interactions in real time is increasing exponentially. Applications include protein-protein, protein-peptide, DNA-protein, DNA-DNA, and lipid-protein interactions. Such techniques have been applied to, for example, antibody-antigen, receptor-ligand, signal transduction, and nuclear receptor studies. This review outlines the principles of two of the most commonly used instruments and highlights specific operating parameters that will assist in optimising experimental design, data generation, and analysis.

NMR paves the way for atomic level descriptions of sparsely populated, transiently formed biomolecular conformers.

Science.gov (United States)

Sekhar, Ashok; Kay, Lewis E

2013-08-06

The importance of dynamics to biomolecular function is becoming increasingly clear. A description of the structure-function relationship must, therefore, include the role of motion, requiring a shift in paradigm from focus on a single static 3D picture to one where a given biomolecule is considered in terms of an ensemble of interconverting conformers, each with potentially diverse activities. In this Perspective, we describe how recent developments in solution NMR spectroscopy facilitate atomic resolution studies of sparsely populated, transiently formed biomolecular conformations that exchange with the native state. Examples of how this methodology is applied to protein folding and misfolding, ligand binding, and molecular recognition are provided as a means of illustrating both the power of the new techniques and the significant roles that conformationally excited protein states play in biology.

Insights Into the Bifunctional Aphidicolan-16-ß-ol Synthase Through Rapid Biomolecular Modeling Approaches

Directory of Open Access Journals (Sweden)

Max Hirte

2018-04-01

Full Text Available Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modeling techniques offer an alternative route to study the enzyme's reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modeling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modeling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789, and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modeling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially

Insights Into the Bifunctional Aphidicolan-16-ß-ol Synthase Through Rapid Biomolecular Modeling Approaches.

Science.gov (United States)

Hirte, Max; Meese, Nicolas; Mertz, Michael; Fuchs, Monika; Brück, Thomas B

2018-01-01

Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modeling techniques offer an alternative route to study the enzyme's reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modeling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modeling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789, and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modeling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially restricted location of

Insights into the bifunctional Aphidicolan-16-ß-ol synthase through rapid biomolecular modelling approaches

Science.gov (United States)

Hirte, Max; Meese, Nicolas; Mertz, Michael; Fuchs, Monika; Brück, Thomas B.

2018-04-01

Diterpene synthases catalyze complex, multi-step C-C coupling reactions thereby converting the universal, aliphatic precursor geranylgeranyl diphosphate into diverse olefinic macrocylces that form the basis for the structural diversity of the diterpene natural product family. Since catalytically relevant crystal structures of diterpene synthases are scarce, homology based biomolecular modelling techniques offer an alternative route to study the enzyme’s reaction mechanism. However, precise identification of catalytically relevant amino acids is challenging since these models require careful preparation and refinement techniques prior to substrate docking studies. Targeted amino acid substitutions in this protein class can initiate premature quenching of the carbocation centered reaction cascade. The structural characterization of those alternative cyclization products allows for elucidation of the cyclization reaction cascade and provides a new source for complex macrocyclic synthons. In this study, new insights into structure and function of the fungal, bifunctional Aphidicolan-16-ß-ol synthase were achieved using a simplified biomolecular modelling strategy. The applied refinement methodologies could rapidly generate a reliable protein-ligand complex, which provides for an accurate in silico identification of catalytically relevant amino acids. Guided by our modelling data, ACS mutations lead to the identification of the catalytically relevant ACS amino acid network I626, T657, Y658, A786, F789 and Y923. Moreover, the ACS amino acid substitutions Y658L and D661A resulted in a premature termination of the cyclization reaction cascade en-route from syn-copalyl diphosphate to Aphidicolan-16-ß-ol. Both ACS mutants generated the diterpene macrocycle syn-copalol and a minor, non-hydroxylated labdane related diterpene, respectively. Our biomolecular modelling and mutational studies suggest that the ACS substrate cyclization occurs in a spatially restricted location

A new approach to implement absorbing boundary condition in biomolecular electrostatics.

Science.gov (United States)

Goni, Md Osman

2013-01-01

This paper discusses a novel approach to employ the absorbing boundary condition in conjunction with the finite-element method (FEM) in biomolecular electrostatics. The introduction of Bayliss-Turkel absorbing boundary operators in electromagnetic scattering problem has been incorporated by few researchers. However, in the area of biomolecular electrostatics, this boundary condition has not been investigated yet. The objective of this paper is twofold. First, to solve nonlinear Poisson-Boltzmann equation using Newton's method and second, to find an efficient and acceptable solution with minimum number of unknowns. In this work, a Galerkin finite-element formulation is used along with a Bayliss-Turkel absorbing boundary operator that explicitly accounts for the open field problem by mapping the Sommerfeld radiation condition from the far field to near field. While the Bayliss-Turkel condition works well when the artificial boundary is far from the scatterer, an acceptable tolerance of error can be achieved with the second order operator. Numerical results on test case with simple sphere show that the treatment is able to reach the same level of accuracy achieved by the analytical method while using a lower grid density. Bayliss-Turkel absorbing boundary condition (BTABC) combined with the FEM converges to the exact solution of scattering problems to within discretization error.

High-speed AFM for Studying Dynamic Biomolecular Processes

Science.gov (United States)

Ando, Toshio

2008-03-01

Biological molecules show their vital activities only in aqueous solutions. It had been one of dreams in biological sciences to directly observe biological macromolecules (protein, DNA) at work under a physiological condition because such observation is straightforward to understanding their dynamic behaviors and functional mechanisms. Optical microscopy has no sufficient spatial resolution and electron microscopy is not applicable to in-liquid samples. Atomic force microscopy (AFM) can visualize molecules in liquids at high resolution but its imaging rate was too low to capture dynamic biological processes. This slow imaging rate is because AFM employs mechanical probes (cantilevers) and mechanical scanners to detect the sample height at each pixel. It is quite difficult to quickly move a mechanical device of macroscopic size with sub-nanometer accuracy without producing unwanted vibrations. It is also difficult to maintain the delicate contact between a probe tip and fragile samples. Two key techniques are required to realize high-speed AFM for biological research; fast feedback control to maintain a weak tip-sample interaction force and a technique to suppress mechanical vibrations of the scanner. Various efforts have been carried out in the past decade to materialize high-speed AFM. The current high-speed AFM can capture images on video at 30-60 frames/s for a scan range of 250nm and 100 scan lines, without significantly disturbing week biomolecular interaction. Our recent studies demonstrated that this new microscope can reveal biomolecular processes such as myosin V walking along actin tracks and association/dissociation dynamics of chaperonin GroEL-GroES that occurs in a negatively cooperative manner. The capacity of nanometer-scale visualization of dynamic processes in liquids will innovate on biological research. In addition, it will open a new way to study dynamic chemical/physical processes of various phenomena that occur at the liquid-solid interfaces.

Large-scale event extraction from literature with multi-level gene normalization.

Directory of Open Access Journals (Sweden)

Sofie Van Landeghem

Full Text Available Text mining for the life sciences aims to aid database curation, knowledge summarization and information retrieval through the automated processing of biomedical texts. To provide comprehensive coverage and enable full integration with existing biomolecular database records, it is crucial that text mining tools scale up to millions of articles and that their analyses can be unambiguously linked to information recorded in resources such as UniProt, KEGG, BioGRID and NCBI databases. In this study, we investigate how fully automated text mining of complex biomolecular events can be augmented with a normalization strategy that identifies biological concepts in text, mapping them to identifiers at varying levels of granularity, ranging from canonicalized symbols to unique gene and proteins and broad gene families. To this end, we have combined two state-of-the-art text mining components, previously evaluated on two community-wide challenges, and have extended and improved upon these methods by exploiting their complementary nature. Using these systems, we perform normalization and event extraction to create a large-scale resource that is publicly available, unique in semantic scope, and covers all 21.9 million PubMed abstracts and 460 thousand PubMed Central open access full-text articles. This dataset contains 40 million biomolecular events involving 76 million gene/protein mentions, linked to 122 thousand distinct genes from 5032 species across the full taxonomic tree. Detailed evaluations and analyses reveal promising results for application of this data in database and pathway curation efforts. The main software components used in this study are released under an open-source license. Further, the resulting dataset is freely accessible through a novel API, providing programmatic and customized access (http://www.evexdb.org/api/v001/. Finally, to allow for large-scale bioinformatic analyses, the entire resource is available for bulk download from

Interacting with the biomolecular solvent accessible surface via a haptic feedback device

Directory of Open Access Journals (Sweden)

Hayward Steven

2009-10-01

Full Text Available Abstract Background From the 1950s computer based renderings of molecules have been produced to aid researchers in their understanding of biomolecular structure and function. A major consideration for any molecular graphics software is the ability to visualise the three dimensional structure of the molecule. Traditionally, this was accomplished via stereoscopic pairs of images and later realised with three dimensional display technologies. Using a haptic feedback device in combination with molecular graphics has the potential to enhance three dimensional visualisation. Although haptic feedback devices have been used to feel the interaction forces during molecular docking they have not been used explicitly as an aid to visualisation. Results A haptic rendering application for biomolecular visualisation has been developed that allows the user to gain three-dimensional awareness of the shape of a biomolecule. By using a water molecule as the probe, modelled as an oxygen atom having hard-sphere interactions with the biomolecule, the process of exploration has the further benefit of being able to determine regions on the molecular surface that are accessible to the solvent. This gives insight into how awkward it is for a water molecule to gain access to or escape from channels and cavities, indicating possible entropic bottlenecks. In the case of liver alcohol dehydrogenase bound to the inhibitor SAD, it was found that there is a channel just wide enough for a single water molecule to pass through. Placing the probe coincident with crystallographic water molecules suggests that they are sometimes located within small pockets that provide a sterically stable environment irrespective of hydrogen bonding considerations. Conclusion By using the software, named HaptiMol ISAS (available from http://www.haptimol.co.uk, one can explore the accessible surface of biomolecules using a three-dimensional input device to gain insights into the shape and water

Systematic methods for defining coarse-grained maps in large biomolecules.

Science.gov (United States)

Zhang, Zhiyong

2015-01-01

Large biomolecules are involved in many important biological processes. It would be difficult to use large-scale atomistic molecular dynamics (MD) simulations to study the functional motions of these systems because of the computational expense. Therefore various coarse-grained (CG) approaches have attracted rapidly growing interest, which enable simulations of large biomolecules over longer effective timescales than all-atom MD simulations. The first issue in CG modeling is to construct CG maps from atomic structures. In this chapter, we review the recent development of a novel and systematic method for constructing CG representations of arbitrarily complex biomolecules, in order to preserve large-scale and functionally relevant essential dynamics (ED) at the CG level. In this ED-CG scheme, the essential dynamics can be characterized by principal component analysis (PCA) on a structural ensemble, or elastic network model (ENM) of a single atomic structure. Validation and applications of the method cover various biological systems, such as multi-domain proteins, protein complexes, and even biomolecular machines. The results demonstrate that the ED-CG method may serve as a very useful tool for identifying functional dynamics of large biomolecules at the CG level.

A new strategy for imaging biomolecular events through interactions between liquid crystals and oil-in-water emulsions.

Science.gov (United States)

Hu, Qiong-Zheng; Jang, Chang-Hyun

2012-11-21

In this study, we demonstrate a new strategy to image biomolecular events through interactions between liquid crystals (LCs) and oil-in-water emulsions. The optical response had a dark appearance when a nematic LC, 4-cyano-4'-pentylbiphenyl (5CB), is in contact with emulsion droplets of glyceryl trioleate (GT). In contrast, the optical response had a bright appearance when 5CB is in contact with GT emulsions decorated with surfactants such as sodium oleate. Since lipase can hydrolyze GT and produce oleic acid, the optical response also displays a bright appearance after 5CB has been in contact with a mixture of lipase and GT emulsions. These results indicate the feasibility of monitoring biomolecular events through interactions between LCs and oil-in-water emulsions.

The universal statistical distributions of the affinity, equilibrium constants, kinetics and specificity in biomolecular recognition.

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Xiliang Zheng

2015-04-01

Full Text Available We uncovered the universal statistical laws for the biomolecular recognition/binding process. We quantified the statistical energy landscapes for binding, from which we can characterize the distributions of the binding free energy (affinity, the equilibrium constants, the kinetics and the specificity by exploring the different ligands binding with a particular receptor. The results of the analytical studies are confirmed by the microscopic flexible docking simulations. The distribution of binding affinity is Gaussian around the mean and becomes exponential near the tail. The equilibrium constants of the binding follow a log-normal distribution around the mean and a power law distribution in the tail. The intrinsic specificity for biomolecular recognition measures the degree of discrimination of native versus non-native binding and the optimization of which becomes the maximization of the ratio of the free energy gap between the native state and the average of non-native states versus the roughness measured by the variance of the free energy landscape around its mean. The intrinsic specificity obeys a Gaussian distribution near the mean and an exponential distribution near the tail. Furthermore, the kinetics of binding follows a log-normal distribution near the mean and a power law distribution at the tail. Our study provides new insights into the statistical nature of thermodynamics, kinetics and function from different ligands binding with a specific receptor or equivalently specific ligand binding with different receptors. The elucidation of distributions of the kinetics and free energy has guiding roles in studying biomolecular recognition and function through small-molecule evolution and chemical genetics.

Micro- and nanodevices integrated with biomolecular probes.

Science.gov (United States)

Alapan, Yunus; Icoz, Kutay; Gurkan, Umut A

2015-12-01

Understanding how biomolecules, proteins and cells interact with their surroundings and other biological entities has become the fundamental design criterion for most biomedical micro- and nanodevices. Advances in biology, medicine, and nanofabrication technologies complement each other and allow us to engineer new tools based on biomolecules utilized as probes. Engineered micro/nanosystems and biomolecules in nature have remarkably robust compatibility in terms of function, size, and physical properties. This article presents the state of the art in micro- and nanoscale devices designed and fabricated with biomolecular probes as their vital constituents. General design and fabrication concepts are presented and three major platform technologies are highlighted: microcantilevers, micro/nanopillars, and microfluidics. Overview of each technology, typical fabrication details, and application areas are presented by emphasizing significant achievements, current challenges, and future opportunities. Copyright © 2015 Elsevier Inc. All rights reserved.

Proceedings of the international advisory committee on 'biomolecular dynamics instrument DNA' and the workshop on 'biomolecular dynamics backscattering spectrometers'

International Nuclear Information System (INIS)

Arai, Masatoshi; Aizawa, Kazuya; Nakajima, Kenji; Shibata, Kaoru; Takahashi, Nobuaki

2008-08-01

A workshop entitled 'Biomolecular Dynamics Backscattering Spectrometers' was held on February 27th - 29th, 2008 at J-PARC Center, Japan Atomic Energy Agency. This workshop was planned to be held for aiming to realize an innovative neutron backscattering instrument, namely DNA, in the MLF and thus four leading scientists in the field of neutron backscattering instruments were invited as the International Advisory Committee (IAC member: Dr. Dan Neumann (Chair); Prof. Ferenc Mezei; Dr. Hannu Mutka; Dr. Philip Tregenna-Piggott) for DNA from institutes in the United States, France and Switzerland, where backscattering instruments are in-service. It was therefore held in the form of lecture anterior and then in the form of the committee posterior. This report includes the executive summary of the IAC and materials of the presentations in the IAC and the workshop. (author)

Theoretical restrictions on longest implicit time scales in Markov state models of biomolecular dynamics

Science.gov (United States)

Sinitskiy, Anton V.; Pande, Vijay S.

2018-01-01

Markov state models (MSMs) have been widely used to analyze computer simulations of various biomolecular systems. They can capture conformational transitions much slower than an average or maximal length of a single molecular dynamics (MD) trajectory from the set of trajectories used to build the MSM. A rule of thumb claiming that the slowest implicit time scale captured by an MSM should be comparable by the order of magnitude to the aggregate duration of all MD trajectories used to build this MSM has been known in the field. However, this rule has never been formally proved. In this work, we present analytical results for the slowest time scale in several types of MSMs, supporting the above rule. We conclude that the slowest implicit time scale equals the product of the aggregate sampling and four factors that quantify: (1) how much statistics on the conformational transitions corresponding to the longest implicit time scale is available, (2) how good the sampling of the destination Markov state is, (3) the gain in statistics from using a sliding window for counting transitions between Markov states, and (4) a bias in the estimate of the implicit time scale arising from finite sampling of the conformational transitions. We demonstrate that in many practically important cases all these four factors are on the order of unity, and we analyze possible scenarios that could lead to their significant deviation from unity. Overall, we provide for the first time analytical results on the slowest time scales captured by MSMs. These results can guide further practical applications of MSMs to biomolecular dynamics and allow for higher computational efficiency of simulations.

Raman spectroscopy detects biomolecular changes associated with nanoencapsulated hesperetin treatment in experimental oral carcinogenesis

International Nuclear Information System (INIS)

Gurushankar, K; Gohulkumar, M; Krishnakumar, N; Kumar, Piyush; Murali Krishna, C

2016-01-01

Recently it has been shown that Raman spectroscopy possesses great potential in the investigation of biomolecular changes of tumor tissues with therapeutic drug response in a non-invasive and label-free manner. The present study is designed to investigate the antitumor effect of hespertin-loaded nanoparticles (HETNPs) relative to the efficacy of native hesperetin (HET) in modifying the biomolecular changes during 7,12-dimethyl benz(a)anthracene (DMBA)-induced oral carcinogenesis using a Raman spectroscopic technique. Significant differences in the intensity and shape of the Raman spectra between the control and the experimental tissues at 1800–500 cm −1 were observed. Tumor tissues are characterized by an increase in the relative amount of proteins, nucleic acids, tryptophan and phenylalanine and a decrease in the percentage of lipids when compared to the control tissues. Further, oral administration of HET and its nanoparticulates restored the status of the lipids and significantly decreased the levels of protein and nucleic acid content. Treatment with HETNPs showed a more potent antitumor effect than treatment with native HET, which resulted in an overall reduction in the intensity of several biochemical Raman bands in DMBA-induced oral carcinogenesis being observed. Principal component and linear discriminant analysis (PC–LDA), together with leave-one-out cross validation (LOOCV) on Raman spectra yielded diagnostic sensitivities of 100%, 80%, 91.6% and 65% and specificities of 100%, 65%, 60% and 55% for classification of control versus DMBA, DMBA versus DMBA  +  HET, DMBA versus DMBA  +  HETNPs and DMBA  +  HET versus DMBA  +  HETNPs treated tissue groups, respectively. These results further demonstrate that Raman spectroscopy associated with multivariate statistical algorithms could be a valuable tool for developing a comprehensive understanding of the process of biomolecular changes, and could reveal the signatures of the

The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes.

Science.gov (United States)

van Zundert, G C P; Rodrigues, J P G L M; Trellet, M; Schmitz, C; Kastritis, P L; Karaca, E; Melquiond, A S J; van Dijk, M; de Vries, S J; Bonvin, A M J J

2016-02-22

The prediction of the quaternary structure of biomolecular macromolecules is of paramount importance for fundamental understanding of cellular processes and drug design. In the era of integrative structural biology, one way of increasing the accuracy of modeling methods used to predict the structure of biomolecular complexes is to include as much experimental or predictive information as possible in the process. This has been at the core of our information-driven docking approach HADDOCK. We present here the updated version 2.2 of the HADDOCK portal, which offers new features such as support for mixed molecule types, additional experimental restraints and improved protocols, all of this in a user-friendly interface. With well over 6000 registered users and 108,000 jobs served, an increasing fraction of which on grid resources, we hope that this timely upgrade will help the community to solve important biological questions and further advance the field. The HADDOCK2.2 Web server is freely accessible to non-profit users at http://haddock.science.uu.nl/services/HADDOCK2.2. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biomolecular Markers in Cancer of the Tongue

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Daris Ferrari

2009-01-01

Full Text Available The incidence of tongue cancer is increasing worldwide, and its aggressiveness remains high regardless of treatment. Genetic changes and the expression of abnormal proteins have been frequently reported in the case of head and neck cancers, but the little information that has been published concerning tongue tumours is often contradictory. This review will concentrate on the immunohistochemical expression of biomolecular markers and their relationships with clinical behaviour and prognosis. Most of these proteins are associated with nodal stage, tumour progression and metastases, but there is still controversy concerning their impact on disease-free and overall survival, and treatment response. More extensive clinical studies are needed to identify the patterns of molecular alterations and the most reliable predictors in order to develop tailored anti-tumour strategies based on the targeting of hypoxia markers, vascular and lymphangiogenic factors, epidermal growth factor receptors, intracytoplasmatic signalling and apoptosis.

Towards sensitive, high-throughput, biomolecular assays based on fluorescence lifetime

Science.gov (United States)

Ioanna Skilitsi, Anastasia; Turko, Timothé; Cianfarani, Damien; Barre, Sophie; Uhring, Wilfried; Hassiepen, Ulrich; Léonard, Jérémie

2017-09-01

Time-resolved fluorescence detection for robust sensing of biomolecular interactions is developed by implementing time-correlated single photon counting in high-throughput conditions. Droplet microfluidics is used as a promising platform for the very fast handling of low-volume samples. We illustrate the potential of this very sensitive and cost-effective technology in the context of an enzymatic activity assay based on fluorescently-labeled biomolecules. Fluorescence lifetime detection by time-correlated single photon counting is shown to enable reliable discrimination between positive and negative control samples at a throughput as high as several hundred samples per second.

Small-angle X-ray scattering investigations of biomolecular confinement, loading, and release from liquid-crystalline nanochannel assemblies

Czech Academy of Sciences Publication Activity Database

Angelova, A.; Angelov, Borislav; Garamus, V. M.; Couvreur, P.; Lesieur, S.

2012-01-01

Roč. 3, č. 3 (2012), s. 445-457 ISSN 1948-7185 Institutional research plan: CEZ:AV0Z40500505 Keywords : nanochannels * biomolecular nanostructures * SAXS Subject RIV: CD - Macromolecular Chemistry Impact factor: 6.585, year: 2012

Single-Cell Biomolecular Analysis of Coral Algal Symbionts Reveals Opposing Metabolic Responses to Heat Stress and Expulsion

Directory of Open Access Journals (Sweden)

Katherina Petrou

2018-03-01

Full Text Available The success of corals in nutrient poor environments is largely attributed to the symbiosis between the cnidarian host and its intracellular alga. Warm water anomalies have been shown to destabilize this symbiosis, yet detailed analysis of the effect of temperature and expulsion on cell-specific carbon and nutrient allocation in the symbiont is limited. Here, we exposed colonies of the hard coral Acropora millepora to heat stress and using synchrotron-based infrared microspectroscopy measured the biomolecular profiles of individual in hospite and expelled symbiont cells at an acute state of bleaching. Our results showed symbiont metabolic profiles to be remarkably distinct with heat stress and expulsion, where the two effectors elicited opposing metabolic adjustments independent of treatment or cell type. Elevated temperature resulted in biomolecular changes reflecting cellular stress, with relative increases in free amino acids and phosphorylation of molecules and a concomitant decline in protein content, suggesting protein modification and degradation. This contrasted with the metabolic profiles of expelled symbionts, which showed relative decreases in free amino acids and phosphorylated molecules, but increases in proteins and lipids, suggesting expulsion lessens the overall effect of heat stress on the metabolic signature of the algal symbionts. Interestingly, the combined effects of expulsion and thermal stress were additive, reducing the overall shifts in all biomolecules, with the notable exception of the significant accumulation of lipids and saturated fatty acids. This first use of a single-cell metabolomics approach on the coral symbiosis provides novel insight into coral bleaching and emphasizes the importance of a single-cell approach to demark the cell-to-cell variability in the physiology of coral cellular populations.

Modeling systems-level dynamics: Understanding without mechanistic explanation in integrative systems biology.

Science.gov (United States)

MacLeod, Miles; Nersessian, Nancy J

2015-02-01

In this paper we draw upon rich ethnographic data of two systems biology labs to explore the roles of explanation and understanding in large-scale systems modeling. We illustrate practices that depart from the goal of dynamic mechanistic explanation for the sake of more limited modeling goals. These processes use abstract mathematical formulations of bio-molecular interactions and data fitting techniques which we call top-down abstraction to trade away accurate mechanistic accounts of large-scale systems for specific information about aspects of those systems. We characterize these practices as pragmatic responses to the constraints many modelers of large-scale systems face, which in turn generate more limited pragmatic non-mechanistic forms of understanding of systems. These forms aim at knowledge of how to predict system responses in order to manipulate and control some aspects of them. We propose that this analysis of understanding provides a way to interpret what many systems biologists are aiming for in practice when they talk about the objective of a "systems-level understanding." Copyright © 2014 Elsevier Ltd. All rights reserved.

Foreword [IJEGMBE 2015: India-Japan expert group meeting on biomolecular electronics and organic nanotechnology for environment preservation, Fukuoka (Japan), 23-26 December 2015

International Nuclear Information System (INIS)

2016-01-01

There is increased interest in organic nanotechnology and biomolecular electronics for environmental preservation, and in their anticipated impact on the economics of both the developing and the developed world. Keeping this in mind, the Department of Biological Functions, Graduate School of Life Sciences and Systems Engineering, Kyushu Institute of Technology (KIT), Kitakyushu, Japan, and the Department of Science and Technology Centre on Biomolecular Electronics (DSTCBE), National Physical Laboratory (NPL) jointly organized the India-Japan Workshop on Biomolecular Electronics and Organic Nanotechnology for Environmental Preservation (IJWBME 2009) at NPL, New Delhi from 17 th - 19 th December 2009, IJWBME 2011 at EGRET Himeji, Himeji, from 7 th - 10 th December, Japan, and IJWBME 2013 at Delhi Technological University, New Delhi, from 13 th - 15 th December. The India-Japan Expert Group Meeting on Biomolecular Electronics and Organic Nanotechnology for Environment Preservation (IJEGMBE) will be held from 22 th – 25 th , December, 2015, at Nakamura Centenary Memorial Hall, Kyushu Institute of Technology, Kitakyushu, Japan in association with Delhi Technological University, Delhi, India. Recent years have seen rapid growth in the area of Biomolecular Electronics involving the association and expertise of physicists, biologists, chemists, electronics engineers and information technologists. There is increasing interest in the development of nanotechnology and biomolecular electronic devices for the preservation of our precious environment. In this context, the world of the electronics, which developed on Si semiconductors, is going to change drastically. A paradigm shift towards organic or printed electronics is more likely in the future. The field of organic electronics promises exciting new technologies based on inexpensive and mechanically flexible electronic devices, and is now starting to see commercial success. On the sidelines of this increasingly well

ISAMBARD: an open-source computational environment for biomolecular analysis, modelling and design.

Science.gov (United States)

Wood, Christopher W; Heal, Jack W; Thomson, Andrew R; Bartlett, Gail J; Ibarra, Amaurys Á; Brady, R Leo; Sessions, Richard B; Woolfson, Derek N

2017-10-01

The rational design of biomolecules is becoming a reality. However, further computational tools are needed to facilitate and accelerate this, and to make it accessible to more users. Here we introduce ISAMBARD, a tool for structural analysis, model building and rational design of biomolecules. ISAMBARD is open-source, modular, computationally scalable and intuitive to use. These features allow non-experts to explore biomolecular design in silico. ISAMBARD addresses a standing issue in protein design, namely, how to introduce backbone variability in a controlled manner. This is achieved through the generalization of tools for parametric modelling, describing the overall shape of proteins geometrically, and without input from experimentally determined structures. This will allow backbone conformations for entire folds and assemblies not observed in nature to be generated de novo, that is, to access the 'dark matter of protein-fold space'. We anticipate that ISAMBARD will find broad applications in biomolecular design, biotechnology and synthetic biology. A current stable build can be downloaded from the python package index (https://pypi.python.org/pypi/isambard/) with development builds available on GitHub (https://github.com/woolfson-group/) along with documentation, tutorial material and all the scripts used to generate the data described in this paper. d.n.woolfson@bristol.ac.uk or chris.wood@bristol.ac.uk. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Perspective: Watching low-frequency vibrations of water in biomolecular recognition by THz spectroscopy

Science.gov (United States)

Xu, Yao; Havenith, Martina

2015-11-01

Terahertz (THz) spectroscopy has turned out to be a powerful tool which is able to shed new light on the role of water in biomolecular processes. The low frequency spectrum of the solvated biomolecule in combination with MD simulations provides deep insights into the collective hydrogen bond dynamics on the sub-ps time scale. The absorption spectrum between 1 THz and 10 THz of solvated biomolecules is sensitive to changes in the fast fluctuations of the water network. Systematic studies on mutants of antifreeze proteins indicate a direct correlation between biological activity and a retardation of the (sub)-ps hydration dynamics at the protein binding site, i.e., a "hydration funnel." Kinetic THz absorption studies probe the temporal changes of THz absorption during a biological process, and give access to the kinetics of the coupled protein-hydration dynamics. When combined with simulations, the observed results can be explained in terms of a two-tier model involving a local binding and a long range influence on the hydration bond dynamics of the water around the binding site that highlights the significance of the changes in the hydration dynamics at recognition site for biomolecular recognition. Water is shown to assist molecular recognition processes.

BioMagResBank (BMRB) as a partner in the Worldwide Protein Data Bank (wwPDB): new policies affecting biomolecular NMR depositions

International Nuclear Information System (INIS)

Markley, John L.; Ulrich, Eldon L.; Berman, Helen M.; Henrick, Kim; Nakamura, Haruki; Akutsu, Hideo

2008-01-01

We describe the role of the BioMagResBank (BMRB) within the Worldwide Protein Data Bank (wwPDB) and recent policies affecting the deposition of biomolecular NMR data. All PDB depositions of structures based on NMR data must now be accompanied by experimental restraints. A scheme has been devised that allows depositors to specify a representative structure and to define residues within that structure found experimentally to be largely unstructured. The BMRB now accepts coordinate sets representing three-dimensional structural models based on experimental NMR data of molecules of biological interest that fall outside the guidelines of the Protein Data Bank (i.e., the molecule is a peptide with 23 or fewer residues, a polynucleotide with 3 or fewer residues, a polysaccharide with 3 or fewer sugar residues, or a natural product), provided that the coordinates are accompanied by representation of the covalent structure of the molecule (atom connectivity), assigned NMR chemical shifts, and the structural restraints used in generating model. The BMRB now contains an archive of NMR data for metabolites and other small molecules found in biological systems

Orientation of biomolecular assemblies in a microfluidic jet

International Nuclear Information System (INIS)

Priebe, M; Kalbfleisch, S; Tolkiehn, M; Salditt, T; Koester, S; Abel, B; Davies, R J

2010-01-01

We have investigated multilamellar lipid assemblies in a microfluidic jet, operating at high shear rates of the order of 10 7 s -1 . Compared to classical Couette cells or rheometers, the shear rate was increased by at least 2-3 orders of magnitude, and the sample volume was scaled down correspondingly. At the same time, the jet is characterized by high extensional stress due to elongational flow. A focused synchrotron x-ray beam was used to measure the structure and orientation of the lipid assemblies in the jet. The diffraction patterns indicate conventional multilamellar phases, aligned with the membrane normals oriented along the velocity gradient of the jet. The results indicate that the setup may be well suited for coherent diffractive imaging of oriented biomolecular assemblies and macromolecules at the future x-ray free electron laser (XFEL) sources.

ANCA: Anharmonic Conformational Analysis of Biomolecular Simulations.

Science.gov (United States)

Parvatikar, Akash; Vacaliuc, Gabriel S; Ramanathan, Arvind; Chennubhotla, S Chakra

2018-05-08

Anharmonicity in time-dependent conformational fluctuations is noted to be a key feature of functional dynamics of biomolecules. Although anharmonic events are rare, long-timescale (μs-ms and beyond) simulations facilitate probing of such events. We have previously developed quasi-anharmonic analysis to resolve higher-order spatial correlations and characterize anharmonicity in biomolecular simulations. In this article, we have extended this toolbox to resolve higher-order temporal correlations and built a scalable Python package called anharmonic conformational analysis (ANCA). ANCA has modules to: 1) measure anharmonicity in the form of higher-order statistics and its variation as a function of time, 2) output a storyboard representation of the simulations to identify key anharmonic conformational events, and 3) identify putative anharmonic conformational substates and visualization of transitions between these substates. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Design of an embedded inverse-feedforward biomolecular tracking controller for enzymatic reaction processes

OpenAIRE

Foo, Mathias; Kim, Jongrae; Sawlekar, Rucha; Bates, Declan G.

2017-01-01

Feedback control is widely used in chemical engineering to improve the performance and robustness of chemical processes. Feedback controllers require a ‘subtractor’ that is able to compute the error between the process output and the reference signal. In the case of embedded biomolecular control circuits, subtractors designed using standard chemical reaction network theory can only realise one-sided subtraction, rendering standard controller design approaches inadequate. Here, we show how a b...

RPYFMM: Parallel adaptive fast multipole method for Rotne-Prager-Yamakawa tensor in biomolecular hydrodynamics simulations

Science.gov (United States)

Guan, W.; Cheng, X.; Huang, J.; Huber, G.; Li, W.; McCammon, J. A.; Zhang, B.

2018-06-01

RPYFMM is a software package for the efficient evaluation of the potential field governed by the Rotne-Prager-Yamakawa (RPY) tensor interactions in biomolecular hydrodynamics simulations. In our algorithm, the RPY tensor is decomposed as a linear combination of four Laplace interactions, each of which is evaluated using the adaptive fast multipole method (FMM) (Greengard and Rokhlin, 1997) where the exponential expansions are applied to diagonalize the multipole-to-local translation operators. RPYFMM offers a unified execution on both shared and distributed memory computers by leveraging the DASHMM library (DeBuhr et al., 2016, 2018). Preliminary numerical results show that the interactions for a molecular system of 15 million particles (beads) can be computed within one second on a Cray XC30 cluster using 12,288 cores, while achieving approximately 54% strong-scaling efficiency.

A biomolecular proportional integral controller based on feedback regulations of protein level and activity.

Science.gov (United States)

Mairet, Francis

2018-02-01

Homeostasis is the capacity of living organisms to keep internal conditions regulated at a constant level, despite environmental fluctuations. Integral feedback control is known to play a key role in this behaviour. Here, I show that a feedback system involving transcriptional and post-translational regulations of the same executor protein acts as a proportional integral (PI) controller, leading to enhanced transient performances in comparison with a classical integral loop. Such a biomolecular controller-which I call a level and activity-PI controller (LA-PI)-is involved in the regulation of ammonium uptake by Escherichia coli through the transporter AmtB. The P II molecules, which reflect the nitrogen status of the cell, inhibit both the production of AmtB and its activity (via the NtrB-NtrC system and the formation of a complex with GlnK, respectively). Other examples of LA-PI controller include copper and zinc transporters, and the redox regulation in photosynthesis. This scheme has thus emerged through evolution in many biological systems, surely because of the benefits it offers in terms of performances (rapid and perfect adaptation) and economy (protein production according to needs).

Pre-Clinical Tests of an Integrated CMOS Biomolecular Sensor for Cardiac Diseases Diagnosis.

Science.gov (United States)

Lee, Jen-Kuang; Wang, I-Shun; Huang, Chi-Hsien; Chen, Yih-Fan; Huang, Nien-Tsu; Lin, Chih-Ting

2017-11-26

Coronary artery disease and its related complications pose great threats to human health. In this work, we aim to clinically evaluate a CMOS field-effect biomolecular sensor for cardiac biomarkers, cardiac-specific troponin-I (cTnI), N -terminal prohormone brain natriuretic peptide (NT-proBNP), and interleukin-6 (IL-6). The CMOS biosensor is implemented via a standard commercialized 0.35 μm CMOS process. To validate the sensing characteristics, in buffer conditions, the developed CMOS biosensor has identified the detection limits of IL-6, cTnI, and NT-proBNP as being 45 pM, 32 pM, and 32 pM, respectively. In clinical serum conditions, furthermore, the developed CMOS biosensor performs a good correlation with an enzyme-linked immuno-sorbent assay (ELISA) obtained from a hospital central laboratory. Based on this work, the CMOS field-effect biosensor poses good potential for accomplishing the needs of a point-of-care testing (POCT) system for heart disease diagnosis.

Native fluorescence detection of biomolecular and pharmaceutical compounds in capillary electrophoresis: detector designs, performance and applications: A review

NARCIS (Netherlands)

de Kort, B.J.; de Jong, G.J.; Somsen, G.W.

2013-01-01

This review treats the coupling of capillary electrophoresis (CE) with fluorescence detection (Flu) for the analysis of natively fluorescent biomolecular and pharmaceutical compounds. CE-Flu combines the excellent separation efficiency of CE with the high selectivity and sensitivity of Flu. In

Tibialis anterior muscle needle biopsy and sensitive biomolecular methods: a useful tool in myotonic dystrophy type 1

Directory of Open Access Journals (Sweden)

S. Iachettini

2015-10-01

Full Text Available Myotonic dystrophy type 1 (DM1 is a neuromuscular disorder caused by a CTG repeat expansion in 3’UTR of DMPK gene. This mutation causes accumulation of toxic RNA in nuclear foci leading to splicing misregulation of specific genes. In view of future clinical trials with antisense oligonucleotides in DM1 patients, it is important to set up sensitive and minimally-invasive tools to monitor the efficacy of treatments on skeletal muscle. A tibialis anterior (TA muscle sample of about 60 mg was obtained from 5 DM1 patients and 5 healthy subjects through a needle biopsy. A fragment of about 40 mg was used for histological examination and a fragment of about 20 mg was used for biomolecular analysis. The TA fragments obtained with the minimally-invasive needle biopsy technique is enough to perform all the histopathological and biomolecular evaluations useful to monitor a clinical trial on DM1 patients.

Hybrid organic semiconductor lasers for bio-molecular sensing.

Science.gov (United States)

Haughey, Anne-Marie; Foucher, Caroline; Guilhabert, Benoit; Kanibolotsky, Alexander L; Skabara, Peter J; Burley, Glenn; Dawson, Martin D; Laurand, Nicolas

2014-01-01

Bio-functionalised luminescent organic semiconductors are attractive for biophotonics because they can act as efficient laser materials while simultaneously interacting with molecules. In this paper, we present and discuss a laser biosensor platform that utilises a gain layer made of such an organic semiconductor material. The simple structure of the sensor and its operation principle are described. Nanolayer detection is shown experimentally and analysed theoretically in order to assess the potential and the limits of the biosensor. The advantage conferred by the organic semiconductor is explained, and comparisons to laser sensors using alternative dye-doped materials are made. Specific biomolecular sensing is demonstrated, and routes to functionalisation with nucleic acid probes, and future developments opened up by this achievement, are highlighted. Finally, attractive formats for sensing applications are mentioned, as well as colloidal quantum dots, which in the future could be used in conjunction with organic semiconductors.

Design rules for biomolecular adhesion: lessons from force measurements.

Science.gov (United States)

Leckband, Deborah

2010-01-01

Cell adhesion to matrix, other cells, or pathogens plays a pivotal role in many processes in biomolecular engineering. Early macroscopic methods of quantifying adhesion led to the development of quantitative models of cell adhesion and migration. The more recent use of sensitive probes to quantify the forces that alter or manipulate adhesion proteins has revealed much greater functional diversity than was apparent from population average measurements of cell adhesion. This review highlights theoretical and experimental methods that identified force-dependent molecular properties that are central to the biological activity of adhesion proteins. Experimental and theoretical methods emphasized in this review include the surface force apparatus, atomic force microscopy, and vesicle-based probes. Specific examples given illustrate how these tools have revealed unique properties of adhesion proteins and their structural origins.

FY 2000 report on the results of the R and D of the fusion domain. Volume 3. Biomolecular mechanism and design; 2000 nendo yugo ryoiki kenkyu kaihatsu. 3. Biomolecular mechanism and design

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

For the purpose of creating cells/tissue assemblies and the molecular machine that substitute for self-organizing and self-repairing functions of a living body outside the body, the basic technology research was conducted, and the FY 2000 results were reported. In the study of 3D cell and tissue module engineering, the following were conducted: study of the surface modification and functional expression of biomaterials, study of the mechanical stress to cartilaginous cells and the response, development of the production method of biodegradable synthetic polymer porous materials, study of organism hard tissue materials/bone remodeling and cultured bone transportation, development of zinc-releasing calcium phosphate ceramics. In the study of biomolecular mechanism and design, 1D unidirectional movement of microtubules by applying microlithography technology, structural study of kinesin-family molecular motor by low temperature microscope, ribozyme and the application to leukemia, basic study on assessment of chemical substances by human cultured cells, study of a low molecule detection system using nucleic acid and peptide. (NEDO)

Optimal use of data in parallel tempering simulations for the construction of discrete-state Markov models of biomolecular dynamics.

Science.gov (United States)

Prinz, Jan-Hendrik; Chodera, John D; Pande, Vijay S; Swope, William C; Smith, Jeremy C; Noé, Frank

2011-06-28

Parallel tempering (PT) molecular dynamics simulations have been extensively investigated as a means of efficient sampling of the configurations of biomolecular systems. Recent work has demonstrated how the short physical trajectories generated in PT simulations of biomolecules can be used to construct the Markov models describing biomolecular dynamics at each simulated temperature. While this approach describes the temperature-dependent kinetics, it does not make optimal use of all available PT data, instead estimating the rates at a given temperature using only data from that temperature. This can be problematic, as some relevant transitions or states may not be sufficiently sampled at the temperature of interest, but might be readily sampled at nearby temperatures. Further, the comparison of temperature-dependent properties can suffer from the false assumption that data collected from different temperatures are uncorrelated. We propose here a strategy in which, by a simple modification of the PT protocol, the harvested trajectories can be reweighted, permitting data from all temperatures to contribute to the estimated kinetic model. The method reduces the statistical uncertainty in the kinetic model relative to the single temperature approach and provides estimates of transition probabilities even for transitions not observed at the temperature of interest. Further, the method allows the kinetics to be estimated at temperatures other than those at which simulations were run. We illustrate this method by applying it to the generation of a Markov model of the conformational dynamics of the solvated terminally blocked alanine peptide.

A biomolecular recognition approach for the functionalization of cellulose with gold nanoparticles.

Science.gov (United States)

Almeida, A; Rosa, A M M; Azevedo, A M; Prazeres, D M F

2017-09-01

Materials with new and improved functionalities can be obtained by modifying cellulose with gold nanoparticles (AuNPs) via the in situ reduction of a gold precursor or the deposition or covalent immobilization of pre-synthesized AuNPs. Here, we present an alternative biomolecular recognition approach to functionalize cellulose with biotin-AuNPs that relies on a complex of 2 recognition elements: a ZZ-CBM3 fusion that combines a carbohydrate-binding module (CBM) with the ZZ fragment of the staphylococcal protein A and an anti-biotin antibody. Paper and cellulose microparticles with AuNPs immobilized via the ZZ-CBM3:anti-biotin IgG supramolecular complex displayed an intense red color, whereas essentially no color was detected when AuNPs were deposited over the unmodified materials. Scanning electron microscopy analysis revealed a homogeneous distribution of AuNPs when immobilized via ZZ-CBM3:anti-biotin IgG complexes and aggregation of AuNPs when deposited over paper, suggesting that color differences are due to interparticle plasmon coupling effects. The approach could be used to functionalize paper substrates and cellulose nanocrystals with AuNPs. More important, however, is the fact that the occurrence of a biomolecular recognition event between the CBM-immobilized antibody and its specific, AuNP-conjugated antigen is signaled by red color. This opens up the way for the development of simple and straightforward paper/cellulose-based tests where detection of a target analyte can be made by direct use of color signaling. Copyright © 2017 John Wiley & Sons, Ltd.

Investigation of the Human Disease Osteogenesis Imperfecta: A Research-Based Introduction to Concepts and Skills in Biomolecular Analysis

Science.gov (United States)

Mate, Karen; Sim, Alistair; Weidenhofer, Judith; Milward, Liz; Scott, Judith

2013-01-01

A blended approach encompassing problem-based learning (PBL) and structured inquiry was used in this laboratory exercise based on the congenital disease Osteogenesis imperfecta (OI), to introduce commonly used techniques in biomolecular analysis within a clinical context. During a series of PBL sessions students were presented with several…

Positrons in biomolecular systems. II

International Nuclear Information System (INIS)

Glass, J.C.; Graf, G.; Costabal, H.; Ewert, D.H.; English, L.

1982-01-01

Pickoff-annihilation parameters, as related to the free volume model, are shown to be indicators of structural fluctuations in membranes and membrane bound proteins. Nitrous oxide anesthetic induces lateral rigidity in a membrane, and an anesthetic mechanism is suggested. Conformational changes of (Na + ,K + )ATPase in natural membrane are observed with ATP and Mg-ion binding. New positron applications to active transport and photosynthetic systems are suggested. (Auth.)

A common-path phase-shift interferometry surface plasmon imaging system

Science.gov (United States)

Su, Y.-T.; Chen, Shean-Jen; Yeh, T.-L.

2005-03-01

A biosensing imaging system is proposed based on the integration of surface plasmon resonance (SPR) and common-path phase-shift interferometry (PSI) techniques to measure the two-dimensional spatial phase variation caused by biomolecular interactions upon a sensing chip. The SPR phase imaging system can offer high resolution and high-throughout screening capabilities to analyze microarray biomolecular interaction without the need for additional labeling. With the long-term stability advantage of the common-path PSI technique even with external disturbances such as mechanical vibration, buffer flow noise, and laser unstable issue, the system can match the demand of real-time kinetic study for biomolecular interaction analysis (BIA). The SPR-PSI imaging system has achieved a detection limit of 2×10-7 refraction index change, a long-term phase stability of 2.5x10-4π rms over four hours, and a spatial phase resolution of 10-3 π with a lateral resolution of 100μm.

Parity Violation in Chiral Molecules: From Theory towards Spectroscopic Experiment and the Evolution of Biomolecular Homochirality

CERN Multimedia

CERN. Geneva

2016-01-01

The observation of biomolecular homochirality can be considered as a quasi-fossil of the evolution of life [1], the interpretation of which has been an open question for more than a century, with numerous related hypotheses, but no definitive answers. We shall briefly discuss the current status and the relation to the other two questions. The discovery of parity violation led to important developm...

Toxicity evaluation of PEDOT/biomolecular composites intended for neural communication electrodes

International Nuclear Information System (INIS)

Asplund, M; Thaning, E; Von Holst, H; Lundberg, J; Sandberg-Nordqvist, A C; Kostyszyn, B; Inganaes, O

2009-01-01

Electrodes coated with the conducting polymer poly(3,4-ethylene dioxythiophene) (PEDOT) possess attractive electrochemical properties for stimulation or recording in the nervous system. Biomolecules, added as counter ions in electropolymerization, could further improve the biomaterial properties, eliminating the need for surfactant counter ions in the process. Such PEDOT/biomolecular composites, using heparin or hyaluronic acid, have previously been investigated electrochemically. In the present study, their biocompatibility is evaluated. An agarose overlay assay using L929 fibroblasts, and elution and direct contact tests on human neuroblastoma SH-SY5Y cells are applied to investigate cytotoxicity in vitro. PEDOT:heparin was further evaluated in vivo through polymer-coated implants in rodent cortex. No cytotoxic response was seen to any of the PEDOT materials tested. The examination of cortical tissue exposed to polymer-coated implants showed extensive glial scarring irrespective of implant material (Pt:polymer or Pt). However, quantification of immunological response, through distance measurements from implant site to closest neuron and counting of ED1+ cell density around implant, was comparable to those of platinum controls. These results indicate that PEDOT:heparin surfaces were non-cytotoxic and show no marked difference in immunological response in cortical tissue compared to pure platinum controls.

A Quick-responsive DNA Nanotechnology Device for Bio-molecular Homeostasis Regulation.

Science.gov (United States)

Wu, Songlin; Wang, Pei; Xiao, Chen; Li, Zheng; Yang, Bing; Fu, Jieyang; Chen, Jing; Wan, Neng; Ma, Cong; Li, Maoteng; Yang, Xiangliang; Zhan, Yi

2016-08-10

Physiological processes such as metabolism, cell apoptosis and immune responses, must be strictly regulated to maintain their homeostasis and achieve their normal physiological functions. The speed with which bio-molecular homeostatic regulation occurs directly determines the ability of an organism to adapt to conditional changes. To produce a quick-responsive regulatory system that can be easily utilized for various types of homeostasis, a device called nano-fingers that facilitates the regulation of physiological processes was constructed using DNA origami nanotechnology. This nano-fingers device functioned in linked open and closed phases using two types of DNA tweezers, which were covalently coupled with aptamers that captured specific molecules when the tweezer arms were sufficiently close. Via this specific interaction mechanism, certain physiological processes could be simultaneously regulated from two directions by capturing one biofactor and releasing the other to enhance the regulatory capacity of the device. To validate the universal application of this device, regulation of the homeostasis of the blood coagulant thrombin was attempted using the nano-fingers device. It was successfully demonstrated that this nano-fingers device achieved coagulation buffering upon the input of fuel DNA. This nano-device could also be utilized to regulate the homeostasis of other types of bio-molecules.

Dose controlled low energy electron irradiator for biomolecular films.

Science.gov (United States)

Kumar, S V K; Tare, Satej T; Upalekar, Yogesh V; Tsering, Thupten

2016-03-01

We have developed a multi target, Low Energy Electron (LEE), precise dose controlled irradiator for biomolecular films. Up to seven samples can be irradiated one after another at any preset electron energy and dose under UHV conditions without venting the chamber. In addition, one more sample goes through all the steps except irradiation, which can be used as control for comparison with the irradiated samples. All the samples are protected against stray electron irradiation by biasing them at -20 V during the entire period, except during irradiation. Ethernet based communication electronics hardware, LEE beam control electronics and computer interface were developed in house. The user Graphical User Interface to control the irradiation and dose measurement was developed using National Instruments Lab Windows CVI. The working and reliability of the dose controlled irradiator has been fully tested over the electron energy range of 0.5 to 500 eV by studying LEE induced single strand breaks to ΦX174 RF1 dsDNA.

Dose controlled low energy electron irradiator for biomolecular films

Energy Technology Data Exchange (ETDEWEB)

Kumar, S. V. K., E-mail: svkk@tifr.res.in; Tare, Satej T.; Upalekar, Yogesh V.; Tsering, Thupten [Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005 (India)

2016-03-15

We have developed a multi target, Low Energy Electron (LEE), precise dose controlled irradiator for biomolecular films. Up to seven samples can be irradiated one after another at any preset electron energy and dose under UHV conditions without venting the chamber. In addition, one more sample goes through all the steps except irradiation, which can be used as control for comparison with the irradiated samples. All the samples are protected against stray electron irradiation by biasing them at −20 V during the entire period, except during irradiation. Ethernet based communication electronics hardware, LEE beam control electronics and computer interface were developed in house. The user Graphical User Interface to control the irradiation and dose measurement was developed using National Instruments Lab Windows CVI. The working and reliability of the dose controlled irradiator has been fully tested over the electron energy range of 0.5 to 500 eV by studying LEE induced single strand breaks to ΦX174 RF1 dsDNA.

Computational methods to study the structure and dynamics of biomolecules and biomolecular processes from bioinformatics to molecular quantum mechanics

CERN Document Server

2014-01-01

Since the second half of the 20th century machine computations have played a critical role in science and engineering. Computer-based techniques have become especially important in molecular biology, since they often represent the only viable way to gain insights into the behavior of a biological system as a whole. The complexity of biological systems, which usually needs to be analyzed on different time- and size-scales and with different levels of accuracy, requires the application of different approaches, ranging from comparative analysis of sequences and structural databases, to the analysis of networks of interdependence between cell components and processes, through coarse-grained modeling to atomically detailed simulations, and finally to molecular quantum mechanics. This book provides a comprehensive overview of modern computer-based techniques for computing the structure, properties and dynamics of biomolecules and biomolecular processes. The twenty-two chapters, written by scientists from all over t...

Biomolecular System Design: Architecture, Synthesis, and Simulation

OpenAIRE

Chiang , Katherine

2015-01-01

The advancements in systems and synthetic biology have been broadening the range of realizable systems with increasing complexity both in vitro and in vivo. Systems for digital logic operations, signal processing, analog computation, program flow control, as well as those composed of different functions – for example an on-site diagnostic system based on multiple biomarker measurements and signal processing – have been realized successfully. However, the efforts to date tend to tackle each de...

Stable isotope applications in biomolecular structure and mechanisms. A meeting to bring together producers and users of stable-isotope-labeled compounds to assess current and future needs

International Nuclear Information System (INIS)

Trewhella, J.; Cross, T.A.; Unkefer, C.J.

1994-12-01

Knowledge of biomolecular structure is a prerequisite for understanding biomolecular function, and stable isotopes play an increasingly important role in structure determination of biological molecules. The first Conference on Stable Isotope Applications in Biomolecular Structure and Mechanisms was held in Santa Fe, New Mexico, March 27--31, 1994. More than 120 participants from 8 countries and 44 institutions reviewed significant developments, discussed the most promising applications for stable isotopes, and addressed future needs and challenges. Participants focused on applications of stable isotopes for studies of the structure and function of proteins, peptides, RNA, and DNA. Recent advances in NMR techniques neutron scattering, EPR, and vibrational spectroscopy were highlighted in addition to the production and synthesis of labeled compounds. This volume includes invited speaker and poster presentations as well as a set of reports from discussion panels that focused on the needs of the scientific community and the potential roles of private industry, the National Stable Isotope Resource, and the National High Magnetic Field Laboratory in serving those needs. This is the leading abstract. Individual papers are processed separately for the database

Stable isotope applications in biomolecular structure and mechanisms. A meeting to bring together producers and users of stable-isotope-labeled compounds to assess current and future needs

Energy Technology Data Exchange (ETDEWEB)

Trewhella, J.; Cross, T.A.; Unkefer, C.J. [eds.

1994-12-01

Knowledge of biomolecular structure is a prerequisite for understanding biomolecular function, and stable isotopes play an increasingly important role in structure determination of biological molecules. The first Conference on Stable Isotope Applications in Biomolecular Structure and Mechanisms was held in Santa Fe, New Mexico, March 27--31, 1994. More than 120 participants from 8 countries and 44 institutions reviewed significant developments, discussed the most promising applications for stable isotopes, and addressed future needs and challenges. Participants focused on applications of stable isotopes for studies of the structure and function of proteins, peptides, RNA, and DNA. Recent advances in NMR techniques neutron scattering, EPR, and vibrational spectroscopy were highlighted in addition to the production and synthesis of labeled compounds. This volume includes invited speaker and poster presentations as well as a set of reports from discussion panels that focused on the needs of the scientific community and the potential roles of private industry, the National Stable Isotope Resource, and the National High Magnetic Field Laboratory in serving those needs. This is the leading abstract. Individual papers are processed separately for the database.

Conformation of bovine submaxillary mucin layers on hydrophobic surface as studied by biomolecular probes

DEFF Research Database (Denmark)

Pakkanen, Kirsi I.; Madsen, Jan Busk; Lee, Seunghwan

2015-01-01

In the present study, the conformational changes of bovine submaxillary mucin (BSM) adsorbed on a hydrophobic surface (polystyrene (PS)) as a function of concentration in bulk solution (up to 2mg/mL) have been investigated with biomolecular probe-based approaches, including bicinchoninic acid (BCA),enzyme-linkedimmunosorbentassay(EIA...... solution. Adsorbed masses of BSM onto hydrophobic surface, as probe by BCA, showed a continuously increasing trend up to 2mg/mL. But, the signals from EIA and ELLA, which probe the concentration of available unglycosylatedC-terminals and the central glycosylated regions, respectively, showed complicated...

Allosteric transitions of supramolecular systems explored by network models: application to chaperonin GroEL.

Directory of Open Access Journals (Sweden)

Zheng Yang

2009-04-01

Full Text Available Identification of pathways involved in the structural transitions of biomolecular systems is often complicated by the transient nature of the conformations visited across energy barriers and the multiplicity of paths accessible in the multidimensional energy landscape. This task becomes even more challenging in exploring molecular systems on the order of megadaltons. Coarse-grained models that lend themselves to analytical solutions appear to be the only possible means of approaching such cases. Motivated by the utility of elastic network models for describing the collective dynamics of biomolecular systems and by the growing theoretical and experimental evidence in support of the intrinsic accessibility of functional substates, we introduce a new method, adaptive anisotropic network model (aANM, for exploring functional transitions. Application to bacterial chaperonin GroEL and comparisons with experimental data, results from action minimization algorithm, and previous simulations support the utility of aANM as a computationally efficient, yet physically plausible, tool for unraveling potential transition pathways sampled by large complexes/assemblies. An important outcome is the assessment of the critical inter-residue interactions formed/broken near the transition state(s, most of which involve conserved residues.

A variational approach to moment-closure approximations for the kinetics of biomolecular reaction networks

Science.gov (United States)

Bronstein, Leo; Koeppl, Heinz

2018-01-01

Approximate solutions of the chemical master equation and the chemical Fokker-Planck equation are an important tool in the analysis of biomolecular reaction networks. Previous studies have highlighted a number of problems with the moment-closure approach used to obtain such approximations, calling it an ad hoc method. In this article, we give a new variational derivation of moment-closure equations which provides us with an intuitive understanding of their properties and failure modes and allows us to correct some of these problems. We use mixtures of product-Poisson distributions to obtain a flexible parametric family which solves the commonly observed problem of divergences at low system sizes. We also extend the recently introduced entropic matching approach to arbitrary ansatz distributions and Markov processes, demonstrating that it is a special case of variational moment closure. This provides us with a particularly principled approximation method. Finally, we extend the above approaches to cover the approximation of multi-time joint distributions, resulting in a viable alternative to process-level approximations which are often intractable.

A Starting Point for Fluorescence-Based Single-Molecule Measurements in Biomolecular Research

Directory of Open Access Journals (Sweden)

Alexander Gust

2014-09-01

Full Text Available Single-molecule fluorescence techniques are ideally suited to provide information about the structure-function-dynamics relationship of a biomolecule as static and dynamic heterogeneity can be easily detected. However, what type of single-molecule fluorescence technique is suited for which kind of biological question and what are the obstacles on the way to a successful single-molecule microscopy experiment? In this review, we provide practical insights into fluorescence-based single-molecule experiments aiming for scientists who wish to take their experiments to the single-molecule level. We especially focus on fluorescence resonance energy transfer (FRET experiments as these are a widely employed tool for the investigation of biomolecular mechanisms. We will guide the reader through the most critical steps that determine the success and quality of diffusion-based confocal and immobilization-based total internal reflection fluorescence microscopy. We discuss the specific chemical and photophysical requirements that make fluorescent dyes suitable for single-molecule fluorescence experiments. Most importantly, we review recently emerged photoprotection systems as well as passivation and immobilization strategies that enable the observation of fluorescently labeled molecules under biocompatible conditions. Moreover, we discuss how the optical single-molecule toolkit has been extended in recent years to capture the physiological complexity of a cell making it even more relevant for biological research.

Automating large-scale reactor systems

International Nuclear Information System (INIS)

Kisner, R.A.

1985-01-01

This paper conveys a philosophy for developing automated large-scale control systems that behave in an integrated, intelligent, flexible manner. Methods for operating large-scale systems under varying degrees of equipment degradation are discussed, and a design approach that separates the effort into phases is suggested. 5 refs., 1 fig

Reliability of large and complex systems

CERN Document Server

Kolowrocki, Krzysztof

2014-01-01

Reliability of Large and Complex Systems, previously titled Reliability of Large Systems, is an innovative guide to the current state and reliability of large and complex systems. In addition to revised and updated content on the complexity and safety of large and complex mechanisms, this new edition looks at the reliability of nanosystems, a key research topic in nanotechnology science. The author discusses the importance of safety investigation of critical infrastructures that have aged or have been exposed to varying operational conditions. This reference provides an asympt

Evolução biomolecular homoquiral: a origem e a amplificação da quiralidade nas moléculas da vida Homochiral biomolecular evolution: the origin and the amplification of chirality in life molecules

Directory of Open Access Journals (Sweden)

José Augusto R. Rodrigues

2010-01-01

Full Text Available The fact that biologically relevant molecules exist only as one of the two enantiomers is a fascinating example of complete symmetry breaking of chirality and has long intrigued our curiosity. The origin of this selective chirality has remained a fundamental enigma with regard to the origin of life since the time of Pasteur, 160 years ago. The symmetry breaking processes, which include autocatalytic crystallization, asymmetric autocatalysis, spontaneous crystallization, adsorption and polymerization of amino acids on mineral surfaces, provide new insights into the origin of biomolecular homochirality.

Database management system for large container inspection system

International Nuclear Information System (INIS)

Gao Wenhuan; Li Zheng; Kang Kejun; Song Binshan; Liu Fang

1998-01-01

Large Container Inspection System (LCIS) based on radiation imaging technology is a powerful tool for the Customs to check the contents inside a large container without opening it. The author has discussed a database application system, as a part of Signal and Image System (SIS), for the LCIS. The basic requirements analysis was done first. Then the selections of computer hardware, operating system, and database management system were made according to the technology and market products circumstance. Based on the above considerations, a database application system with central management and distributed operation features has been implemented

Workflow management in large distributed systems

International Nuclear Information System (INIS)

Legrand, I; Newman, H; Voicu, R; Dobre, C; Grigoras, C

2011-01-01

The MonALISA (Monitoring Agents using a Large Integrated Services Architecture) framework provides a distributed service system capable of controlling and optimizing large-scale, data-intensive applications. An essential part of managing large-scale, distributed data-processing facilities is a monitoring system for computing facilities, storage, networks, and the very large number of applications running on these systems in near realtime. All this monitoring information gathered for all the subsystems is essential for developing the required higher-level services—the components that provide decision support and some degree of automated decisions—and for maintaining and optimizing workflow in large-scale distributed systems. These management and global optimization functions are performed by higher-level agent-based services. We present several applications of MonALISA's higher-level services including optimized dynamic routing, control, data-transfer scheduling, distributed job scheduling, dynamic allocation of storage resource to running jobs and automated management of remote services among a large set of grid facilities.

Workflow management in large distributed systems

Science.gov (United States)

Legrand, I.; Newman, H.; Voicu, R.; Dobre, C.; Grigoras, C.

2011-12-01

The MonALISA (Monitoring Agents using a Large Integrated Services Architecture) framework provides a distributed service system capable of controlling and optimizing large-scale, data-intensive applications. An essential part of managing large-scale, distributed data-processing facilities is a monitoring system for computing facilities, storage, networks, and the very large number of applications running on these systems in near realtime. All this monitoring information gathered for all the subsystems is essential for developing the required higher-level services—the components that provide decision support and some degree of automated decisions—and for maintaining and optimizing workflow in large-scale distributed systems. These management and global optimization functions are performed by higher-level agent-based services. We present several applications of MonALISA's higher-level services including optimized dynamic routing, control, data-transfer scheduling, distributed job scheduling, dynamic allocation of storage resource to running jobs and automated management of remote services among a large set of grid facilities.

Potential environmental impacts associated with large-scale herbicide-tolerant GM oilseed rape crops

Directory of Open Access Journals (Sweden)

Fellous Marc

2004-07-01

Full Text Available The Biomolecular Engineering Commission considers that the knowledge acquired in the last three years has provided significant information in reply to the points raised in its review dated 16 February 2001. The Commission has studied the potential environmental impacts associated with large-scale herbicidetolerantGMoilseed rape crops, making a distinction between direct and indirect impacts. Direct impacts stem from the intrinsic properties of herbicide-tolerant GM oilseed rape crops whereas indirect impacts result from practices associated with the farming of these crops. The Commission considers that, in the absence of the use of the herbicide in question in and outside of farmed land, there is no direct environmental risk (development of invasive crops per se associated with the presence of a herbicide-tolerance gene in oilseed rape (or related species. Nevertheless, since the interest of these tolerant crops lies in the use of the herbicide in question, indirect effects, to varying extents, have been identified and must be taken into account: the use of the herbicide in question, applied to agricultural fields containing the herbicide-tolerant crop could lead to an increase in oilseed rape volunteer populations in crop rotations; the selective pressure exerted by non-specific herbicides (to which the crops have been rendered tolerant may be very high in cases of continuous and uncontrolled use of these herbicides, and may result in the persistence of rare events such as the reproduction of fertile interspecies hybrids; the change to the range of herbicides used should be conveyed by more effective weed control and, like any change in farming practices, induce indirect effects on the agri-ecosystem, particularly in terms of changes to weeds and the associated animal life. Accordingly, the Biomolecular Engineering Commission recommends a global approach in terms of the large-scale farming of herbicide-tolerant crops that: accounts for the

Large scale network-centric distributed systems

CERN Document Server

Sarbazi-Azad, Hamid

2014-01-01

A highly accessible reference offering a broad range of topics and insights on large scale network-centric distributed systems Evolving from the fields of high-performance computing and networking, large scale network-centric distributed systems continues to grow as one of the most important topics in computing and communication and many interdisciplinary areas. Dealing with both wired and wireless networks, this book focuses on the design and performance issues of such systems. Large Scale Network-Centric Distributed Systems provides in-depth coverage ranging from ground-level hardware issu

Report on result 1998. Research and development on fusion area. Part 3 (biomolecular mechanism and design); 1998 nendo seika hokokusho. Yugo ryoiki kenkyu kaihatsu daisan bunsatsu (bimolecular mechanism and design)

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

An organism is a molecular mechanical system consisting of nucleic acid, peptide and protein having a self-forming and a self-repairing function. For the purpose of creating cells, tissues and molecular mechanism alternating these biological functions, their basic technology was developed. Concretely, studies were made on three-dimensional cellular structural module engineering and biomolecular mechanism and design. Studies on biological soft tissue resulted in success by giving atmospheric glow discharge treatment to the inner surface of a tubular PVC. An artificial vitreous body was created using PVA hydrogels. In addition, liver cells were successfully cultured for the first time in the world. Studies on biological hard tissue revealed that osteopontin plays a role of a trigger for the initial differentiation of the osteoblast cell. Further, a basic experiment was carried out on the initial response of the cartilage cell. In the research on the molecular mechanism, examination was made on the mechanism of a double-head molecular motor. Examination was also made on the adjustment of the hydrogenase LB film as an electricity/hydrogen energy conversion element and on the biomolecular mechanism and design. (NEDO)

Automatic management software for large-scale cluster system

International Nuclear Information System (INIS)

Weng Yunjian; Chinese Academy of Sciences, Beijing; Sun Gongxing

2007-01-01

At present, the large-scale cluster system faces to the difficult management. For example the manager has large work load. It needs to cost much time on the management and the maintenance of large-scale cluster system. The nodes in large-scale cluster system are very easy to be chaotic. Thousands of nodes are put in big rooms so that some managers are very easy to make the confusion with machines. How do effectively carry on accurate management under the large-scale cluster system? The article introduces ELFms in the large-scale cluster system. Furthermore, it is proposed to realize the large-scale cluster system automatic management. (authors)

Distributed simulation of large computer systems

International Nuclear Information System (INIS)

Marzolla, M.

2001-01-01

Sequential simulation of large complex physical systems is often regarded as a computationally expensive task. In order to speed-up complex discrete-event simulations, the paradigm of Parallel and Distributed Discrete Event Simulation (PDES) has been introduced since the late 70s. The authors analyze the applicability of PDES to the modeling and analysis of large computer system; such systems are increasingly common in the area of High Energy and Nuclear Physics, because many modern experiments make use of large 'compute farms'. Some feasibility tests have been performed on a prototype distributed simulator

"Peak tracking chip" for label-free optical detection of bio-molecular interaction and bulk sensing.

Science.gov (United States)

Bougot-Robin, Kristelle; Li, Shunbo; Zhang, Yinghua; Hsing, I-Ming; Benisty, Henri; Wen, Weijia

2012-10-21

A novel imaging method for bulk refractive index sensing or label-free bio-molecular interaction sensing is presented. This method is based on specially designed "Peak tracking chip" (PTC) involving "tracks" of adjacent resonant waveguide gratings (RWG) "micropads" with slowly evolving resonance position. Using a simple camera the spatial information robustly retrieves the diffraction efficiency, which in turn transduces either the refractive index of the liquids on the tracks or the effective thickness of an immobilized biological layer. Our intrinsically multiplex chip combines tunability and versatility advantages of dielectric guided wave biochips without the need of costly hyperspectral instrumentation. The current success of surface plasmon imaging techniques suggests that our chip proposal could leverage an untapped potential to routinely extend such techniques in a convenient and sturdy optical configuration toward, for instance for large analytes detection. PTC design and fabrication are discussed with challenging process to control micropads properties by varying their period (step of 2 nm) or their duty cycle through the groove width (steps of 4 nm). Through monochromatic imaging of our PTC, we present experimental demonstration of bulk index sensing on the range [1.33-1.47] and of surface biomolecule detection of molecular weight 30 kDa in aqueous solution using different surface densities. A sensitivity of the order of 10(-5) RIU for bulk detection and a sensitivity of the order of ∼10 pg mm(-2) for label-free surface detection are expected, therefore opening a large range of application of our chip based imaging technique. Exploiting and chip design, we expect as well our chip to open new direction for multispectral studies through imaging.

Solving the 0/1 Knapsack Problem by a Biomolecular DNA Computer

Directory of Open Access Journals (Sweden)

Hassan Taghipour

2013-01-01

Full Text Available Solving some mathematical problems such as NP-complete problems by conventional silicon-based computers is problematic and takes so long time. DNA computing is an alternative method of computing which uses DNA molecules for computing purposes. DNA computers have massive degrees of parallel processing capability. The massive parallel processing characteristic of DNA computers is of particular interest in solving NP-complete and hard combinatorial problems. NP-complete problems such as knapsack problem and other hard combinatorial problems can be easily solved by DNA computers in a very short period of time comparing to conventional silicon-based computers. Sticker-based DNA computing is one of the methods of DNA computing. In this paper, the sticker based DNA computing was used for solving the 0/1 knapsack problem. At first, a biomolecular solution space was constructed by using appropriate DNA memory complexes. Then, by the application of a sticker-based parallel algorithm using biological operations, knapsack problem was resolved in polynomial time.

Piezoelectric tuning fork biosensors for the quantitative measurement of biomolecular interactions

International Nuclear Information System (INIS)

Gonzalez, Laura; Maria Benito, Angel; Puig-Vidal, Manel; Otero, Jorge; Rodrigues, Mafalda; Pérez-García, Lluïsa

2015-01-01

The quantitative measurement of biomolecular interactions is of great interest in molecular biology. Atomic force microscopy (AFM) has proved its capacity to act as a biosensor and determine the affinity between biomolecules of interest. Nevertheless, the detection scheme presents certain limitations when it comes to developing a compact biosensor. Recently, piezoelectric quartz tuning forks (QTFs) have been used as laser-free detection sensors for AFM. However, only a few studies along these lines have considered soft biological samples, and even fewer constitute quantified molecular recognition experiments. Here, we demonstrate the capacity of QTF probes to perform specific interaction measurements between biotin–streptavidin complexes in buffer solution. We propose in this paper a variant of dynamic force spectroscopy based on representing adhesion energies E (aJ) against pulling rates v (nm s"–"1). Our results are compared with conventional AFM measurements and show the great potential of these sensors in molecular interaction studies. (paper)

H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations.

Science.gov (United States)

Anandakrishnan, Ramu; Aguilar, Boris; Onufriev, Alexey V

2012-07-01

The accuracy of atomistic biomolecular modeling and simulation studies depend on the accuracy of the input structures. Preparing these structures for an atomistic modeling task, such as molecular dynamics (MD) simulation, can involve the use of a variety of different tools for: correcting errors, adding missing atoms, filling valences with hydrogens, predicting pK values for titratable amino acids, assigning predefined partial charges and radii to all atoms, and generating force field parameter/topology files for MD. Identifying, installing and effectively using the appropriate tools for each of these tasks can be difficult for novice and time-consuming for experienced users. H++ (http://biophysics.cs.vt.edu/) is a free open-source web server that automates the above key steps in the preparation of biomolecular structures for molecular modeling and simulations. H++ also performs extensive error and consistency checking, providing error/warning messages together with the suggested corrections. In addition to numerous minor improvements, the latest version of H++ includes several new capabilities and options: fix erroneous (flipped) side chain conformations for HIS, GLN and ASN, include a ligand in the input structure, process nucleic acid structures and generate a solvent box with specified number of common ions for explicit solvent MD.

Microfluidic Devices for Studying Biomolecular Interactions

Science.gov (United States)

Wilson, Wilbur W.; Garcia, Carlos d.; Henry, Charles S.

2006-01-01

Microfluidic devices for monitoring biomolecular interactions have been invented. These devices are basically highly miniaturized liquid-chromatography columns. They are intended to be prototypes of miniature analytical devices of the laboratory on a chip type that could be fabricated rapidly and inexpensively and that, because of their small sizes, would yield analytical results from very small amounts of expensive analytes (typically, proteins). Other advantages to be gained by this scaling down of liquid-chromatography columns may include increases in resolution and speed, decreases in the consumption of reagents, and the possibility of performing multiple simultaneous and highly integrated analyses by use of multiple devices of this type, each possibly containing multiple parallel analytical microchannels. The principle of operation is the same as that of a macroscopic liquid-chromatography column: The column is a channel packed with particles, upon which are immobilized molecules of the protein of interest (or one of the proteins of interest if there are more than one). Starting at a known time, a solution or suspension containing molecules of the protein or other substance of interest is pumped into the channel at its inlet. The liquid emerging from the outlet of the channel is monitored to detect the molecules of the dissolved or suspended substance(s). The time that it takes these molecules to flow from the inlet to the outlet is a measure of the degree of interaction between the immobilized and the dissolved or suspended molecules. Depending on the precise natures of the molecules, this measure can be used for diverse purposes: examples include screening for solution conditions that favor crystallization of proteins, screening for interactions between drugs and proteins, and determining the functions of biomolecules.

Systems engineering for very large systems

Science.gov (United States)

Lewkowicz, Paul E.

Very large integrated systems have always posed special problems for engineers. Whether they are power generation systems, computer networks or space vehicles, whenever there are multiple interfaces, complex technologies or just demanding customers, the challenges are unique. 'Systems engineering' has evolved as a discipline in order to meet these challenges by providing a structured, top-down design and development methodology for the engineer. This paper attempts to define the general class of problems requiring the complete systems engineering treatment and to show how systems engineering can be utilized to improve customer satisfaction and profit ability. Specifically, this work will focus on a design methodology for the largest of systems, not necessarily in terms of physical size, but in terms of complexity and interconnectivity.

Multiscale virtual particle based elastic network model (MVP-ENM) for normal mode analysis of large-sized biomolecules.

Science.gov (United States)

Xia, Kelin

2017-12-20

In this paper, a multiscale virtual particle based elastic network model (MVP-ENM) is proposed for the normal mode analysis of large-sized biomolecules. The multiscale virtual particle (MVP) model is proposed for the discretization of biomolecular density data. With this model, large-sized biomolecular structures can be coarse-grained into virtual particles such that a balance between model accuracy and computational cost can be achieved. An elastic network is constructed by assuming "connections" between virtual particles. The connection is described by a special harmonic potential function, which considers the influence from both the mass distributions and distance relations of the virtual particles. Two independent models, i.e., the multiscale virtual particle based Gaussian network model (MVP-GNM) and the multiscale virtual particle based anisotropic network model (MVP-ANM), are proposed. It has been found that in the Debye-Waller factor (B-factor) prediction, the results from our MVP-GNM with a high resolution are as good as the ones from GNM. Even with low resolutions, our MVP-GNM can still capture the global behavior of the B-factor very well with mismatches predominantly from the regions with large B-factor values. Further, it has been demonstrated that the low-frequency eigenmodes from our MVP-ANM are highly consistent with the ones from ANM even with very low resolutions and a coarse grid. Finally, the great advantage of MVP-ANM model for large-sized biomolecules has been demonstrated by using two poliovirus virus structures. The paper ends with a conclusion.

Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)—the effect of biomolecular ligands to balance cell adhesion and stimulated detachment

International Nuclear Information System (INIS)

Teichmann, Juliane; Valtink, Monika; Funk, Richard H W; Engelmann, Katrin; Nitschke, Mirko; Pette, Dagmar; Gramm, Stefan; Werner, Carsten; Härtel, Frauke V; Noll, Thomas

2015-01-01

Two established material systems for thermally stimulated detachment of adherent cells were combined in a cross-linked polymer blend to merge favorable properties. Through this approach poly(N-isopropylacrylamide) (PNiPAAm) with its superior switching characteristic was paired with a poly(vinyl methyl ether)-based composition that allows adjusting physico-chemical and biomolecular properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive coating provides thickness, stiffness and swelling behavior, as well as an apposite density of reactive sites for biomolecular functionalization, as effective tuning parameters to meet specific requirements of a particular cell type regarding initial adhesion and ease of detachment. To illustrate the strength of this approach, the novel cell culture carrier was applied to generate transplantable sheets of human corneal endothelial cells (HCEC). Sheets were grown, detached, and transferred onto planar targets. Cell morphology, viability and functionality were analyzed by immunocytochemistry and determination of transepithelial electrical resistance (TEER) before and after sheet detachment and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells were positive for function-associated marker proteins ZO-1, Na + /K + -ATPase, and paxillin, and extracellular matrix proteins fibronectin, laminin and collagen type IV before and after transfer. Sheet detachment and transfer did not impair cell viability. Subsequently, a potential application in ophthalmology was demonstrated by transplantation onto de-endothelialized porcine corneas in vitro. The novel thermo-responsive cell culture carrier facilitates the generation and transfer of functional HCEC sheets. This paves the way to generate tissue engineered human corneal endothelium as an alternative transplant source for endothelial keratoplasty. (paper)

Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)—the effect of biomolecular ligands to balance cell adhesion and stimulated detachment

Science.gov (United States)

Teichmann, Juliane; Nitschke, Mirko; Pette, Dagmar; Valtink, Monika; Gramm, Stefan; Härtel, Frauke V; Noll, Thomas; Funk, Richard H W; Engelmann, Katrin; Werner, Carsten

2015-01-01

Two established material systems for thermally stimulated detachment of adherent cells were combined in a cross-linked polymer blend to merge favorable properties. Through this approach poly(N-isopropylacrylamide) (PNiPAAm) with its superior switching characteristic was paired with a poly(vinyl methyl ether)-based composition that allows adjusting physico-chemical and biomolecular properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive coating provides thickness, stiffness and swelling behavior, as well as an apposite density of reactive sites for biomolecular functionalization, as effective tuning parameters to meet specific requirements of a particular cell type regarding initial adhesion and ease of detachment. To illustrate the strength of this approach, the novel cell culture carrier was applied to generate transplantable sheets of human corneal endothelial cells (HCEC). Sheets were grown, detached, and transferred onto planar targets. Cell morphology, viability and functionality were analyzed by immunocytochemistry and determination of transepithelial electrical resistance (TEER) before and after sheet detachment and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells were positive for function-associated marker proteins ZO-1, Na+/K+-ATPase, and paxillin, and extracellular matrix proteins fibronectin, laminin and collagen type IV before and after transfer. Sheet detachment and transfer did not impair cell viability. Subsequently, a potential application in ophthalmology was demonstrated by transplantation onto de-endothelialized porcine corneas in vitro. The novel thermo-responsive cell culture carrier facilitates the generation and transfer of functional HCEC sheets. This paves the way to generate tissue engineered human corneal endothelium as an alternative transplant source for endothelial keratoplasty. PMID:27877823

Large solar energy systems within IEA task 14

NARCIS (Netherlands)

Geus, A.C. de; Isakson, P.; Bokhoven, T.P.; Vanoli, K.; Tepe, R.

1996-01-01

Within IEA Task 14 (Advanced Solar Systems) a working group was established dealing with large advanced solar energy systems (the Large Systems Working group). The goal of this working group was to generate a common base of experiences for the design and construction of advanced large solar systems.

Optimization of large-scale heterogeneous system-of-systems models.

Energy Technology Data Exchange (ETDEWEB)

Parekh, Ojas; Watson, Jean-Paul; Phillips, Cynthia Ann; Siirola, John; Swiler, Laura Painton; Hough, Patricia Diane (Sandia National Laboratories, Livermore, CA); Lee, Herbert K. H. (University of California, Santa Cruz, Santa Cruz, CA); Hart, William Eugene; Gray, Genetha Anne (Sandia National Laboratories, Livermore, CA); Woodruff, David L. (University of California, Davis, Davis, CA)

2012-01-01

Decision makers increasingly rely on large-scale computational models to simulate and analyze complex man-made systems. For example, computational models of national infrastructures are being used to inform government policy, assess economic and national security risks, evaluate infrastructure interdependencies, and plan for the growth and evolution of infrastructure capabilities. A major challenge for decision makers is the analysis of national-scale models that are composed of interacting systems: effective integration of system models is difficult, there are many parameters to analyze in these systems, and fundamental modeling uncertainties complicate analysis. This project is developing optimization methods to effectively represent and analyze large-scale heterogeneous system of systems (HSoS) models, which have emerged as a promising approach for describing such complex man-made systems. These optimization methods enable decision makers to predict future system behavior, manage system risk, assess tradeoffs between system criteria, and identify critical modeling uncertainties.

An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles.

Science.gov (United States)

Digiacomo, L; Cardarelli, F; Pozzi, D; Palchetti, S; Digman, M A; Gratton, E; Capriotti, A L; Mahmoudi, M; Caracciolo, G

2017-11-16

Following exposure to biological milieus (e.g. after systemic administration), nanoparticles (NPs) get covered by an outer biomolecular corona (BC) that defines many of their biological outcomes, such as the elicited immune response, biodistribution, and targeting abilities. In spite of this, the role of BC in regulating the cellular uptake and the subcellular trafficking properties of NPs has remained elusive. Here, we tackle this issue by employing multicomponent (MC) lipid NPs, human plasma (HP) and HeLa cells as models for nanoformulations, biological fluids, and target cells, respectively. By conducting confocal fluorescence microscopy experiments and image correlation analyses, we quantitatively demonstrate that the BC promotes a neat switch of the cell entry mechanism and subsequent intracellular trafficking, from macropinocytosis to clathrin-dependent endocytosis. Nano-liquid chromatography tandem mass spectrometry identifies apolipoproteins as the most abundant components of the BC tested here. Interestingly, this class of proteins target the LDL receptors, which are overexpressed in clathrin-enriched membrane domains. Our results highlight the crucial role of BC as an intrinsic trigger of specific NP-cell interactions and biological responses and set the basis for a rational exploitation of the BC for targeted delivery.

ATR-FTIR Spectroscopic Evidence for Biomolecular Phosphorus and Carboxyl Groups Facilitating Bacterial Adhesion to Iron Oxides

Science.gov (United States)

Parikh, Sanjai J.; Mukome, Fungai N.D.; Zhang, Xiaoming

2014-01-01

Attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy has been used to probe the binding of bacteria to hematite (α-Fe2O3) and goethite (α-FeOOH). In situ ATR-FTIR experiments with bacteria (Pseudomonas putida, P. aeruginosa, Escherichia coli), mixed amino acids, polypeptide extracts, deoxyribonucleic acid (DNA), and a suite of model compounds were conducted. These compounds represent carboxyl, catecholate, amide, and phosphate groups present in siderophores, amino acids, polysaccharides, phospholipids, and DNA. Due in part to the ubiquitous presence of carboxyl groups in biomolecules, numerous IR peaks corresponding to outer-sphere or unbound (1400 cm−1) and inner-sphere (1310-1320 cm−1) coordinated carboxyl groups are noted following reaction of bacteria and biomolecules with α-Fe2O3 and α-FeOOH. However, the data also reveal that the presence of low-level amounts (i.e., 0.45-0.79%) of biomolecular phosphorous groups result in strong IR bands at ~1043 cm−1, corresponding to inner-sphere Fe-O-P bonds, underscoring the importance of bacteria associated P-containing groups in biomolecule and cell adhesion. Spectral comparisons also reveal slightly greater P-O-Fe contributions for bacteria (Pseudomonad, E. coli) deposited on α-FeOOH, as compared to α-Fe2O3. This data demonstrates that slight differences in bacterial adhesion to Fe oxides can be attributed to bacterial species and Fe-oxide minerals. However, more importantly, the strong binding affinity of phosphate in all bacteria samples to both Fe-oxides results in the formation of inner-sphere Fe-O-P bonds, signifying the critical role of biomolecular P in the initiation of bacterial adhesion. PMID:24859052

Zwitterionic Silane Copolymer for Ultra-Stable and Bright Biomolecular Probes Based on Fluorescent Quantum Dot Nanoclusters.

Science.gov (United States)

Dembele, Fatimata; Tasso, Mariana; Trapiella-Alfonso, Laura; Xu, Xiangzhen; Hanafi, Mohamed; Lequeux, Nicolas; Pons, Thomas

2017-05-31

Fluorescent semiconductor quantum dots (QDs) exhibit several unique properties that make them suitable candidates for biomolecular sensing, including high brightness, photostability, broad excitation, and narrow emission spectra. Assembling these QDs into robust and functionalizable nanosized clusters (QD-NSCs) can provide fluorescent probes that are several orders of magnitude brighter than individual QDs, thus allowing an even greater sensitivity of detection with simplified instrumentation. However, the formation of compact, antifouling, functionalizable, and stable QD-NSCs remains a challenging task, especially for a use at ultralow concentrations for single-molecule detection. Here, we describe the development of fluorescent QD-NSCs envisioned as a tool for fast and sensitive biomolecular recognition. First, QDs were assembled into very compact 100-150 nm diameter spherical aggregates; the final QD-NSCs were obtained by growing a cross-linked silica shell around these aggregates. Hydrolytic stability in several concentration and pH conditions is a key requirement for a potential and efficient single-molecule detection tool. However, the hydrolysis of Si-O-Si bonds leads to desorption of monosilane-based surface groups at very low silica concentrations or in a slightly basic medium. Thus, we designed a novel multidentate copolymer composed of multiple silane as well as zwitterionic monomers. Coating silica beads with this multidentate copolymer provided a robust surface chemistry that was demonstrated to be stable against hydrolysis, even at low concentrations. Copolymer-coated silica beads also showed low fouling properties and high colloidal stability in saline solutions. Furthermore, incorporation of additional azido-monomers enabled easy functionalization of QD-NSCs using copper-free bio-orthogonal cyclooctyne-azide click chemistry, as demonstrated by a biotin-streptavidin affinity test.

Fires in large scale ventilation systems

International Nuclear Information System (INIS)

Gregory, W.S.; Martin, R.A.; White, B.W.; Nichols, B.D.; Smith, P.R.; Leslie, I.H.; Fenton, D.L.; Gunaji, M.V.; Blythe, J.P.

1991-01-01

This paper summarizes the experience gained simulating fires in large scale ventilation systems patterned after ventilation systems found in nuclear fuel cycle facilities. The series of experiments discussed included: (1) combustion aerosol loading of 0.61x0.61 m HEPA filters with the combustion products of two organic fuels, polystyrene and polymethylemethacrylate; (2) gas dynamic and heat transport through a large scale ventilation system consisting of a 0.61x0.61 m duct 90 m in length, with dampers, HEPA filters, blowers, etc.; (3) gas dynamic and simultaneous transport of heat and solid particulate (consisting of glass beads with a mean aerodynamic diameter of 10μ) through the large scale ventilation system; and (4) the transport of heat and soot, generated by kerosene pool fires, through the large scale ventilation system. The FIRAC computer code, designed to predict fire-induced transients in nuclear fuel cycle facility ventilation systems, was used to predict the results of experiments (2) through (4). In general, the results of the predictions were satisfactory. The code predictions for the gas dynamics, heat transport, and particulate transport and deposition were within 10% of the experimentally measured values. However, the code was less successful in predicting the amount of soot generation from kerosene pool fires, probably due to the fire module of the code being a one-dimensional zone model. The experiments revealed a complicated three-dimensional combustion pattern within the fire room of the ventilation system. Further refinement of the fire module within FIRAC is needed. (orig.)

Large-scale Complex IT Systems

OpenAIRE

Sommerville, Ian; Cliff, Dave; Calinescu, Radu; Keen, Justin; Kelly, Tim; Kwiatkowska, Marta; McDermid, John; Paige, Richard

2011-01-01

This paper explores the issues around the construction of large-scale complex systems which are built as 'systems of systems' and suggests that there are fundamental reasons, derived from the inherent complexity in these systems, why our current software engineering methods and techniques cannot be scaled up to cope with the engineering challenges of constructing such systems. It then goes on to propose a research and education agenda for software engineering that identifies the major challen...

Large-scale complex IT systems

OpenAIRE

Sommerville, Ian; Cliff, Dave; Calinescu, Radu; Keen, Justin; Kelly, Tim; Kwiatkowska, Marta; McDermid, John; Paige, Richard

2012-01-01

12 pages, 2 figures This paper explores the issues around the construction of large-scale complex systems which are built as 'systems of systems' and suggests that there are fundamental reasons, derived from the inherent complexity in these systems, why our current software engineering methods and techniques cannot be scaled up to cope with the engineering challenges of constructing such systems. It then goes on to propose a research and education agenda for software engineering that ident...

Compressed sensing and the reconstruction of ultrafast 2D NMR data: Principles and biomolecular applications.

Science.gov (United States)

Shrot, Yoav; Frydman, Lucio

2011-04-01

A topic of active investigation in 2D NMR relates to the minimum number of scans required for acquiring this kind of spectra, particularly when these are dictated by sampling rather than by sensitivity considerations. Reductions in this minimum number of scans have been achieved by departing from the regular sampling used to monitor the indirect domain, and relying instead on non-uniform sampling and iterative reconstruction algorithms. Alternatively, so-called "ultrafast" methods can compress the minimum number of scans involved in 2D NMR all the way to a minimum number of one, by spatially encoding the indirect domain information and subsequently recovering it via oscillating field gradients. Given ultrafast NMR's simultaneous recording of the indirect- and direct-domain data, this experiment couples the spectral constraints of these orthogonal domains - often calling for the use of strong acquisition gradients and large filter widths to fulfill the desired bandwidth and resolution demands along all spectral dimensions. This study discusses a way to alleviate these demands, and thereby enhance the method's performance and applicability, by combining spatial encoding with iterative reconstruction approaches. Examples of these new principles are given based on the compressed-sensed reconstruction of biomolecular 2D HSQC ultrafast NMR data, an approach that we show enables a decrease of the gradient strengths demanded in this type of experiments by up to 80%. Copyright © 2011 Elsevier Inc. All rights reserved.

Uma abordagem visual para análise comparativa de redes biomoleculares com apoio de diagramas de Venn

OpenAIRE

Henry Heberle

2014-01-01

Sistemas biológicos podem ser representados por redes que armazenam não apenas informações de conectividade, mas também informações de características de seus nós. No contexto biomolecular, esses nós podem representar proteínas, metabólitos, entre outros tipos de moléculas. Cada molécula possui características anotadas e armazenadas em bases de dados como o Gene Ontology. A comparação visual dessas redes depende de ferramentas que permitam o usuário identificar diferenças e semelhanças entre ...

Versatile single-molecule multi-color excitation and detection fluorescence setup for studying biomolecular dynamics

KAUST Repository

Sobhy, M. A.

2011-11-07

Single-molecule fluorescence imaging is at the forefront of tools applied to study biomolecular dynamics both in vitro and in vivo. The ability of the single-molecule fluorescence microscope to conduct simultaneous multi-color excitation and detection is a key experimental feature that is under continuous development. In this paper, we describe in detail the design and the construction of a sophisticated and versatile multi-color excitation and emission fluorescence instrument for studying biomolecular dynamics at the single-molecule level. The setup is novel, economical and compact, where two inverted microscopes share a laser combiner module with six individual laser sources that extend from 400 to 640 nm. Nonetheless, each microscope can independently and in a flexible manner select the combinations, sequences, and intensities of the excitation wavelengths. This high flexibility is achieved by the replacement of conventional mechanical shutters with acousto-optic tunable filter (AOTF). The use of AOTF provides major advancement by controlling the intensities, duration, and selection of up to eight different wavelengths with microsecond alternation time in a transparent and easy manner for the end user. To our knowledge this is the first time AOTF is applied to wide-field total internal reflection fluorescence (TIRF) microscopy even though it has been commonly used in multi-wavelength confocal microscopy. The laser outputs from the combiner module are coupled to the microscopes by two sets of four single-mode optic fibers in order to allow for the optimization of the TIRF angle for each wavelength independently. The emission is split into two or four spectral channels to allow for the simultaneous detection of up to four different fluorophores of wide selection and using many possible excitation and photoactivation schemes. We demonstrate the performance of this new setup by conducting two-color alternating excitation single-molecule fluorescence resonance energy

Phase sensitive spectral domain interferometry for label free biomolecular interaction analysis and biosensing applications

Science.gov (United States)

Chirvi, Sajal

Biomolecular interaction analysis (BIA) plays vital role in wide variety of fields, which include biomedical research, pharmaceutical industry, medical diagnostics, and biotechnology industry. Study and quantification of interactions between natural biomolecules (proteins, enzymes, DNA) and artificially synthesized molecules (drugs) is routinely done using various labeled and label-free BIA techniques. Labeled BIA (Chemiluminescence, Fluorescence, Radioactive) techniques suffer from steric hindrance of labels on interaction site, difficulty of attaching labels to molecules, higher cost and time of assay development. Label free techniques with real time detection capabilities have demonstrated advantages over traditional labeled techniques. The gold standard for label free BIA is surface Plasmon resonance (SPR) that detects and quantifies the changes in refractive index of the ligand-analyte complex molecule with high sensitivity. Although SPR is a highly sensitive BIA technique, it requires custom-made sensor chips and is not well suited for highly multiplexed BIA required in high throughput applications. Moreover implementation of SPR on various biosensing platforms is limited. In this research work spectral domain phase sensitive interferometry (SD-PSI) has been developed for label-free BIA and biosensing applications to address limitations of SPR and other label free techniques. One distinct advantage of SD-PSI compared to other label-free techniques is that it does not require use of custom fabricated biosensor substrates. Laboratory grade, off-the-shelf glass or plastic substrates of suitable thickness with proper surface functionalization are used as biosensor chips. SD-PSI is tested on four separate BIA and biosensing platforms, which include multi-well plate, flow cell, fiber probe with integrated optics and fiber tip biosensor. Sensitivity of 33 ng/ml for anti-IgG is achieved using multi-well platform. Principle of coherence multiplexing for multi

Trust dynamics in a large system implementation

DEFF Research Database (Denmark)

Schlichter, Bjarne Rerup; Rose, Jeremy

2013-01-01

outcomes, but largely ignored the dynamics of trust relations. Giddens, as part of his study of modernity, theorises trust dynamics in relation to abstract social systems, though without focusing on information systems. We use Giddens’ concepts to investigate evolving trust relationships in a longitudinal......A large information systems implementation (such as Enterprise Resource Planning systems) relies on the trust of its stakeholders to succeed. Such projects impact diverse groups of stakeholders, each with their legitimate interests and expectations. Levels of stakeholder trust can be expected...... case analysis of a large Integrated Hospital System implementation for the Faroe Islands. Trust relationships suffered a serious breakdown, but the project was able to recover and meet its goals. We develop six theoretical propositions theorising the relationship between trust and project outcomes...

Modelling small-angle scattering data from complex protein-lipid systems

DEFF Research Database (Denmark)

Kynde, Søren Andreas Røssell

This thesis consists of two parts. The rst part is divided into five chapters. Chapter 1 gives a general introduction to the bio-molecular systems that have been studied. These are membrane proteins and their lipid environments in the form of phospholipid nanodiscs. Membrane proteins...... the techniques very well suited for the study of the nanodisc system. Chapter 3 explains two different modelling approaches that can be used in the analysis of small-angle scattering data from lipid-protein complexes. These are the continuous approach where the system of interest is modelled as a few regular...... combine the bene ts of each of the methods and give unique structural information about relevant bio-molecular complexes in solution. Chapter 4 describes the work behind a proposal of a small-angle neutron scattering instrument for the European Spallation Source under construction in Lund. The instrument...

Constructing Markov State Models to elucidate the functional conformational changes of complex biomolecules

KAUST Repository

Wang, Wei; Cao, Siqin; Zhu, Lizhe; Huang, Xuhui

2017-01-01

bioengineering applications and rational drug design. Constructing Markov State Models (MSMs) based on large-scale molecular dynamics simulations has emerged as a powerful approach to model functional conformational changes of the biomolecular system

Biomolecular Nano-Flow-Sensor to Measure Near-Surface Flow

Directory of Open Access Journals (Sweden)

Noji Hiroyuki

2009-01-01

Full Text Available Abstract We have proposed and experimentally demonstrated that the measurement of the near-surface flow at the interface between a liquid and solid using a 10 nm-sized biomolecular motor of F1-ATPase as a nano-flow-sensor. For this purpose, we developed a microfluidic test-bed chip to precisely control the liquid flow acting on the F1-ATPase. In order to visualize the rotation of F1-ATPase, several hundreds nanometer-sized particle was immobilized at the rotational axis of F1-ATPase to enhance the rotation to be detected by optical microscopy. The rotational motion of F1-ATPase, which was immobilized on an inner surface of the test-bed chip, was measured to obtain the correlation between the near-surface flow and the rotation speed of F1-ATPase. As a result, we obtained the relationship that the rotation speed of F1-ATPase was linearly decelerated with increasing flow velocity. The mechanism of the correlation between the rotation speed and the near-surface flow remains unclear, however the concept to use biomolecule as a nano-flow-sensor was proofed successfully. (See supplementary material 1 Electronic supplementary material The online version of this article (doi:10.1007/s11671-009-9479-3 contains supplementary material, which is available to authorized users. Click here for file

Status: Large-scale subatmospheric cryogenic systems

International Nuclear Information System (INIS)

Peterson, T.

1989-01-01

In the late 1960's and early 1970's an interest in testing and operating RF cavities at 1.8K motivated the development and construction of four large (300 Watt) 1.8K refrigeration systems. in the past decade, development of successful superconducting RF cavities and interest in obtaining higher magnetic fields with the improved Niobium-Titanium superconductors has once again created interest in large-scale 1.8K refrigeration systems. The L'Air Liquide plant for Tore Supra is a recently commissioned 300 Watt 1.8K system which incorporates new technology, cold compressors, to obtain the low vapor pressure for low temperature cooling. CEBAF proposes to use cold compressors to obtain 5KW at 2.0K. Magnetic refrigerators of 10 Watt capacity or higher at 1.8K are now being developed. The state of the art of large-scale refrigeration in the range under 4K will be reviewed. 28 refs., 4 figs., 7 tabs

Computing in Large-Scale Dynamic Systems

NARCIS (Netherlands)

Pruteanu, A.S.

2013-01-01

Software applications developed for large-scale systems have always been difficult to de- velop due to problems caused by the large number of computing devices involved. Above a certain network size (roughly one hundred), necessary services such as code updating, topol- ogy discovery and data

Review of Transducer Principles for Label-Free Biomolecular Interaction Analysis

Directory of Open Access Journals (Sweden)

Janos Vörös

2011-07-01

Full Text Available Label-free biomolecular interaction analysis is an important technique to study the chemical binding between e.g., protein and protein or protein and small molecule in real-time. The parameters obtained with this technique, such as the affinity, are important for drug development. While the surface plasmon resonance (SPR instruments are most widely used, new types of sensors are emerging. These developments are generally driven by the need for higher throughput, lower sample consumption or by the need of complimentary information to the SPR data. This review aims to give an overview about a wide range of sensor transducers, the working principles and the peculiarities of each technology, e.g., concerning the set-up, sensitivity, sensor size or required sample volume. Starting from optical technologies like the SPR and waveguide based sensors, acoustic sensors like the quartz crystal microbalance (QCM and the film bulk acoustic resonator (FBAR, calorimetric and electrochemical sensors are covered. Technologies long established in the market are presented together with those newly commercially available and with technologies in the early development stage. Finally, the commercially available instruments are summarized together with their sensitivity and the number of sensors usable in parallel and an outlook for potential future developments is given.

Constructing Markov State Models to elucidate the functional conformational changes of complex biomolecules

KAUST Repository

Wang, Wei

2017-10-06

The function of complex biomolecular machines relies heavily on their conformational changes. Investigating these functional conformational changes is therefore essential for understanding the corresponding biological processes and promoting bioengineering applications and rational drug design. Constructing Markov State Models (MSMs) based on large-scale molecular dynamics simulations has emerged as a powerful approach to model functional conformational changes of the biomolecular system with sufficient resolution in both time and space. However, the rapid development of theory and algorithms for constructing MSMs has made it difficult for nonexperts to understand and apply the MSM framework, necessitating a comprehensive guidance toward its theory and practical usage. In this study, we introduce the MSM theory of conformational dynamics based on the projection operator scheme. We further propose a general protocol of constructing MSM to investigate functional conformational changes, which integrates the state-of-the-art techniques for building and optimizing initial pathways, performing adaptive sampling and constructing MSMs. We anticipate this protocol to be widely applied and useful in guiding nonexperts to study the functional conformational changes of large biomolecular systems via the MSM framework. We also discuss the current limitations of MSMs and some alternative methods to alleviate them.

Optimization theory for large systems

CERN Document Server

Lasdon, Leon S

2002-01-01

Important text examines most significant algorithms for optimizing large systems and clarifying relations between optimization procedures. Much data appear as charts and graphs and will be highly valuable to readers in selecting a method and estimating computer time and cost in problem-solving. Initial chapter on linear and nonlinear programming presents all necessary background for subjects covered in rest of book. Second chapter illustrates how large-scale mathematical programs arise from real-world problems. Appendixes. List of Symbols.

Data acquisition system issues for large experiments

International Nuclear Information System (INIS)

Siskind, E.J.

2007-01-01

This talk consists of personal observations on two classes of data acquisition ('DAQ') systems for Silicon trackers in large experiments with which the author has been concerned over the last three or more years. The first half is a classic 'lessons learned' recital based on experience with the high-level debug and configuration of the DAQ system for the GLAST LAT detector. The second half is concerned with a discussion of the promises and pitfalls of using modern (and future) generations of 'system-on-a-chip' ('SOC') or 'platform' field-programmable gate arrays ('FPGAs') in future large DAQ systems. The DAQ system pipeline for the 864k channels of Si tracker in the GLAST LAT consists of five tiers of hardware buffers which ultimately feed into the main memory of the (two-active-node) level-3 trigger processor farm. The data formats and buffer volumes of these tiers are briefly described, as well as the flow control employed between successive tiers. Lessons learned regarding data formats, buffer volumes, and flow control/data discard policy are discussed. The continued development of platform FPGAs containing large amounts of configurable logic fabric, embedded PowerPC hard processor cores, digital signal processing components, large volumes of on-chip buffer memory, and multi-gigabit serial I/O capability permits DAQ system designers to vastly increase the amount of data preprocessing that can be performed in parallel within the DAQ pipeline for detector systems in large experiments. The capabilities of some currently available FPGA families are reviewed, along with the prospects for next-generation families of announced, but not yet available, platform FPGAs. Some experience with an actual implementation is presented, and reconciliation between advertised and achievable specifications is attempted. The prospects for applying these components to space-borne Si tracker detectors are briefly discussed

Nano/biosensors based on large-area graphene

Science.gov (United States)

Ducos, Pedro Jose

Two dimensional materials have properties that make them ideal for applications in chemical and biomolecular sensing. Their high surface/volume ratio implies that all atoms are exposed to the environment, in contrast to three dimensional materials with most atoms shielded from interactions inside the bulk. Graphene additionally has an extremely high carrier mobility, even at ambient temperature and pressure, which makes it ideal as a transduction device. The work presented in this thesis describes large-scale fabrication of Graphene Field Effect Transistors (GFETs), their physical and chemical characterization, and their application as biomolecular sensors. Initially, work was focused on developing an easily scalable fabrication process. A large-area graphene growth, transfer and photolithography process was developed that allowed the scaling of production of devices from a few devices per single transfer in a chip, to over a thousand devices per transfer in a full wafer of fabrication. Two approaches to biomolecules sensing were then investigated, through nanoparticles and through chemical linkers. Gold and platinum Nanoparticles were used as intermediary agents to immobilize a biomolecule. First, gold nanoparticles were monodispersed and functionalized with thiolated probe DNA to yield DNA biosensors with a detection limit of 1 nM and high specificity against noncomplementary DNA. Second, devices are modified with platinum nanoparticles and functionalized with thiolated genetically engineered scFv HER3 antibodies to realize a HER3 biosensor. Sensors retain the high affinity from the scFv fragment and show a detection limit of 300 pM. We then show covalent and non-covalent chemical linkers between graphene and antibodies. The chemical linker 1-pyrenebutanoic acid succinimidyl ester (pyrene) stacks to the graphene by Van der Waals interaction, being a completely non-covalent interaction. The linker 4-Azide-2,3,5,6-tetrafluorobenzoic acid, succinimidyl ester (azide

Economic viability of large-scale fusion systems

Energy Technology Data Exchange (ETDEWEB)

Helsley, Charles E., E-mail: cehelsley@fusionpowercorporation.com; Burke, Robert J.

2014-01-01

A typical modern power generation facility has a capacity of about 1 GWe (Gigawatt electric) per unit. This works well for fossil fuel plants and for most fission facilities for it is large enough to support the sophisticated generation infrastructure but still small enough to be accommodated by most utility grid systems. The size of potential fusion power systems may demand a different viewpoint. The compression and heating of the fusion fuel for ignition requires a large driver, even if it is necessary for only a few microseconds or nanoseconds per energy pulse. The economics of large systems, that can effectively use more of the driver capacity, need to be examined. The assumptions used in this model are specific for the Fusion Power Corporation (FPC) SPRFD process but could be generalized for any system. We assume that the accelerator is the most expensive element of the facility and estimate its cost to be $20 billion. Ignition chambers and fuel handling facilities are projected to cost $1.5 billion each with up to 10 to be serviced by one accelerator. At first this seems expensive but that impression has to be tempered by the energy output that is equal to 35 conventional nuclear plants. This means the cost per kWh is actually low. Using the above assumptions and industry data for generators and heat exchange systems, we conclude that a fully utilized fusion system will produce marketable energy at roughly one half the cost of our current means of generating an equivalent amount of energy from conventional fossil fuel and/or fission systems. Even fractionally utilized systems, i.e. systems used at 25% of capacity, can be cost effective in many cases. In conclusion, SPRFD systems can be scaled to a size and configuration that can be economically viable and very competitive in today's energy market. Electricity will be a significant element in the product mix but synthetic fuels and water may also need to be incorporated to make the large system

Economic viability of large-scale fusion systems

International Nuclear Information System (INIS)

Helsley, Charles E.; Burke, Robert J.

2014-01-01

A typical modern power generation facility has a capacity of about 1 GWe (Gigawatt electric) per unit. This works well for fossil fuel plants and for most fission facilities for it is large enough to support the sophisticated generation infrastructure but still small enough to be accommodated by most utility grid systems. The size of potential fusion power systems may demand a different viewpoint. The compression and heating of the fusion fuel for ignition requires a large driver, even if it is necessary for only a few microseconds or nanoseconds per energy pulse. The economics of large systems, that can effectively use more of the driver capacity, need to be examined. The assumptions used in this model are specific for the Fusion Power Corporation (FPC) SPRFD process but could be generalized for any system. We assume that the accelerator is the most expensive element of the facility and estimate its cost to be $20 billion. Ignition chambers and fuel handling facilities are projected to cost $1.5 billion each with up to 10 to be serviced by one accelerator. At first this seems expensive but that impression has to be tempered by the energy output that is equal to 35 conventional nuclear plants. This means the cost per kWh is actually low. Using the above assumptions and industry data for generators and heat exchange systems, we conclude that a fully utilized fusion system will produce marketable energy at roughly one half the cost of our current means of generating an equivalent amount of energy from conventional fossil fuel and/or fission systems. Even fractionally utilized systems, i.e. systems used at 25% of capacity, can be cost effective in many cases. In conclusion, SPRFD systems can be scaled to a size and configuration that can be economically viable and very competitive in today's energy market. Electricity will be a significant element in the product mix but synthetic fuels and water may also need to be incorporated to make the large system economically

Modeling and simulation of large HVDC systems

Energy Technology Data Exchange (ETDEWEB)

Jin, H.; Sood, V.K.

1993-01-01

This paper addresses the complexity and the amount of work in preparing simulation data and in implementing various converter control schemes and the excessive simulation time involved in modelling and simulation of large HVDC systems. The Power Electronic Circuit Analysis program (PECAN) is used to address these problems and a large HVDC system with two dc links is simulated using PECAN. A benchmark HVDC system is studied to compare the simulation results with those from other packages. The simulation time and results are provided in the paper.

The art and practice of systems biology in medicine: Mapping patterns of relationships

NARCIS (Netherlands)

Greef, J. van der; Martin, S.; Juhasz, P.; Adourian, A.; Plasterer, T.; Verheij, E.R.; McBurney, R.N.

2007-01-01

Systems biology has developed in recent years from a technology-driven enterprise to a new strategic tool in Life Sciences, particularly for innovative drug discovery and drug development. Combining the ultimate in systems phenotyping with in-depth investigations of biomolecular mechanisms will

Estimating the state of large spatio-temporally chaotic systems

International Nuclear Information System (INIS)

Ott, E.; Hunt, B.R.; Szunyogh, I.; Zimin, A.V.; Kostelich, E.J.; Corazza, M.; Kalnay, E.; Patil, D.J.; Yorke, J.A.

2004-01-01

We consider the estimation of the state of a large spatio-temporally chaotic system from noisy observations and knowledge of a system model. Standard state estimation techniques using the Kalman filter approach are not computationally feasible for systems with very many effective degrees of freedom. We present and test a new technique (called a Local Ensemble Kalman Filter), generally applicable to large spatio-temporally chaotic systems for which correlations between system variables evaluated at different points become small at large separation between the points

Advanced manipulator system for large hot cells

International Nuclear Information System (INIS)

Vertut, J.; Moreau, C.; Brossard, J.P.

1981-01-01

Large hot cells can be approached as extrapolated from smaller ones as wide, higher or longer in size with the same concept of using mechanical master slave manipulators and high density windows. This concept leads to a large number of working places and corresponding equipments, with a number of penetrations through the biological protection. When the large cell does not need a permanent operation of number of work places, as in particular to serve PIE machines and maintain the facility, use of servo manipulators with a large supporting unit and extensive use of television appears optimal. The advance on MA 23 and supports will be described including the extra facilities related to manipulators introduction and maintenance. The possibility to combine a powered manipulator and MA 23 (single or pair) on the same boom crane system will be described. An advance control system to bring the minimal dead time to control support movement, associated to the master slave arm operation is under development. The general television system includes over view cameras, associated with the limited number of windows, and manipulators camera. A special new system will be described which brings an automatic control of manipulator cameras and saves operator load and dead time. Full scale tests with MA 23 and support will be discussed. (author)

Needs, opportunities, and options for large scale systems research

Energy Technology Data Exchange (ETDEWEB)

Thompson, G.L.

1984-10-01

The Office of Energy Research was recently asked to perform a study of Large Scale Systems in order to facilitate the development of a true large systems theory. It was decided to ask experts in the fields of electrical engineering, chemical engineering and manufacturing/operations research for their ideas concerning large scale systems research. The author was asked to distribute a questionnaire among these experts to find out their opinions concerning recent accomplishments and future research directions in large scale systems research. He was also requested to convene a conference which included three experts in each area as panel members to discuss the general area of large scale systems research. The conference was held on March 26--27, 1984 in Pittsburgh with nine panel members, and 15 other attendees. The present report is a summary of the ideas presented and the recommendations proposed by the attendees.

Nonlocal Dynamics in Nonlinear Biomolecular and Optical Systems

DEFF Research Database (Denmark)

Larsen, Peter Ulrik Vingaard

2006-01-01

Begrebet ikke-lokalitet nyder større og større interesse indenfor modelleringen af fysiske systemer - og med god grund. At en model er ikke-lokal betyder at for at kunne beskrive dens fysiske egenskaber i et givet punkt korrekt er det ikke tilstrækkeligt blot at betragte omstændighederne netop de...

A magnetic particle micro-trap for large trapping surfaces

KAUST Repository

Gooneratne, Chinthaka P.

2012-01-08

Manipulation of micron-size magnetic particles of the superparamagnetic type contributes significantly in many applications like controlling the antibody/antigen binding process in immunoassays. Specifically, more target biomolecules can be attached/tagged and analyzed since the three dimensional structure of the magnetic particles increases the surface to volume ratio. Additionally, such biomolecular-tagged magnetic particles can be easily manipulated by an external magnetic field due to their superparamagnetic behavior. Therefore, magnetic particle- based immunoassays are extensively applied in micro-flow cytometry. The design of a square-loop micro-trap as a magnetic particle manipulator as well as numerical and experimental analysis is presented. Experimental results showed that the micro-trap could successfully trap and concentrate magnetic particles from a large to a small area with a high spatial range.

A magnetic particle micro-trap for large trapping surfaces

KAUST Repository

Gooneratne, Chinthaka P.; Liang, Cai; Giouroudi, Ioanna; Kosel, Jü rgen

2012-01-01

Manipulation of micron-size magnetic particles of the superparamagnetic type contributes significantly in many applications like controlling the antibody/antigen binding process in immunoassays. Specifically, more target biomolecules can be attached/tagged and analyzed since the three dimensional structure of the magnetic particles increases the surface to volume ratio. Additionally, such biomolecular-tagged magnetic particles can be easily manipulated by an external magnetic field due to their superparamagnetic behavior. Therefore, magnetic particle- based immunoassays are extensively applied in micro-flow cytometry. The design of a square-loop micro-trap as a magnetic particle manipulator as well as numerical and experimental analysis is presented. Experimental results showed that the micro-trap could successfully trap and concentrate magnetic particles from a large to a small area with a high spatial range.

Large-scale Intelligent Transporation Systems simulation

Energy Technology Data Exchange (ETDEWEB)

Ewing, T.; Canfield, T.; Hannebutte, U.; Levine, D.; Tentner, A.

1995-06-01

A prototype computer system has been developed which defines a high-level architecture for a large-scale, comprehensive, scalable simulation of an Intelligent Transportation System (ITS) capable of running on massively parallel computers and distributed (networked) computer systems. The prototype includes the modelling of instrumented ``smart`` vehicles with in-vehicle navigation units capable of optimal route planning and Traffic Management Centers (TMC). The TMC has probe vehicle tracking capabilities (display position and attributes of instrumented vehicles), and can provide 2-way interaction with traffic to provide advisories and link times. Both the in-vehicle navigation module and the TMC feature detailed graphical user interfaces to support human-factors studies. The prototype has been developed on a distributed system of networked UNIX computers but is designed to run on ANL`s IBM SP-X parallel computer system for large scale problems. A novel feature of our design is that vehicles will be represented by autonomus computer processes, each with a behavior model which performs independent route selection and reacts to external traffic events much like real vehicles. With this approach, one will be able to take advantage of emerging massively parallel processor (MPP) systems.

Siemens: Smart Technologies for Large Control Systems

CERN Multimedia

CERN. Geneva; BAKANY, Elisabeth

2015-01-01

The CERN Large Hadron Collider (LHC) is known to be one of the most complex scientific machines ever built by mankind. Its correct functioning relies on the integration of a multitude of interdependent industrial control systems, which provide different and essential services to run and protect the accelerators and experiments. These systems have to deal with several millions of data points (e.g. sensors, actuators, configuration parameters, etc…) which need to be acquired, processed, archived and analysed. Since more than 20 years, CERN and Siemens have developed a strong collaboration to deal with the challenges for these large systems. The presentation will cover the current work on the SCADA (Supervisory Control and Data Acquisition) systems and Data Analytics Frameworks.

Large deviations for noninteracting infinite-particle systems

International Nuclear Information System (INIS)

Donsker, M.D.; Varadhan, S.R.S.

1987-01-01

A large deviation property is established for noninteracting infinite particle systems. Previous large deviation results obtained by the authors involved a single I-function because the cases treated always involved a unique invariant measure for the process. In the context of this paper there is an infinite family of invariant measures and a corresponding infinite family of I-functions governing the large deviations

Entry control system for large populations

International Nuclear Information System (INIS)

Merillat, P.D.

1982-01-01

An Entry Control System has been developed which is appropriate for use at an installation with a large population requiring access over a large area. This is accomplished by centralizing the data base management and enrollment functions and decentralizing the guard-assisted, positive personnel identification and access functions. Current information pertaining to all enrollees is maintained through user-friendly enrollment stations. These stations may be used to enroll individuals, alter their area access authorizations, change expiration dates, and other similar functions. An audit trail of data base alterations is provided to the System Manager. Decentrailized systems exist at each area to which access is controlled. The central system provides these systems with the necessary entry control information to allow them to operate microprocessor-driven entry control devices. The system is comprised of commercially available entry control components and is structured such that it will be able to incorporate improved devices as technology porogresses. Currently, access is granted to individuals who possess a valid credential, have current access authorization, can supply a memorized personal identification number, and whose physical hand dimensions match their profile obtained during enrollment. The entry control devices report misuses as security violations to a Guard Alarm Display and Assessment System

[Large vessels vasculopathy in systemic sclerosis].

Science.gov (United States)

Tejera Segura, Beatriz; Ferraz-Amaro, Iván

2015-12-07

Vasculopathy in systemic sclerosis is a severe, in many cases irreversible, manifestation that can lead to amputation. While the classical clinical manifestations of the disease have to do with the involvement of microcirculation, proximal vessels of upper and lower limbs can also be affected. This involvement of large vessels may be related to systemic sclerosis, vasculitis or atherosclerotic, and the differential diagnosis is not easy. To conduct a proper and early diagnosis, it is essential to start prompt appropriate treatment. In this review, we examine the involvement of large vessels in scleroderma, an understudied manifestation with important prognostic and therapeutic implications. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

REQUIREMENTS FOR SYSTEMS DEVELOPMENT LIFE CYCLE MODELS FOR LARGE-SCALE DEFENSE SYSTEMS

Directory of Open Access Journals (Sweden)

Kadir Alpaslan DEMIR

2015-10-01

Full Text Available TLarge-scale defense system projects are strategic for maintaining and increasing the national defense capability. Therefore, governments spend billions of dollars in the acquisition and development of large-scale defense systems. The scale of defense systems is always increasing and the costs to build them are skyrocketing. Today, defense systems are software intensive and they are either a system of systems or a part of it. Historically, the project performances observed in the development of these systems have been signifi cantly poor when compared to other types of projects. It is obvious that the currently used systems development life cycle models are insuffi cient to address today’s challenges of building these systems. Using a systems development life cycle model that is specifi cally designed for largescale defense system developments and is effective in dealing with today’s and near-future challenges will help to improve project performances. The fi rst step in the development a large-scale defense systems development life cycle model is the identifi cation of requirements for such a model. This paper contributes to the body of literature in the fi eld by providing a set of requirements for system development life cycle models for large-scale defense systems. Furthermore, a research agenda is proposed.

A coordination model for ultra-large scale systems of systems

Directory of Open Access Journals (Sweden)

Manuela L. Bujorianu

2013-11-01

Full Text Available The ultra large multi-agent systems are becoming increasingly popular due to quick decay of the individual production costs and the potential of speeding up the solving of complex problems. Examples include nano-robots, or systems of nano-satellites for dangerous meteorite detection, or cultures of stem cells for organ regeneration or nerve repair. The topics associated with these systems are usually dealt within the theories of intelligent swarms or biologically inspired computation systems. Stochastic models play an important role and they are based on various formulations of the mechanical statistics. In these cases, the main assumption is that the swarm elements have a simple behaviour and that some average properties can be deduced for the entire swarm. In contrast, complex systems in areas like aeronautics are formed by elements with sophisticated behaviour, which are even autonomous. In situations like this, a new approach to swarm coordination is necessary. We present a stochastic model where the swarm elements are communicating autonomous systems, the coordination is separated from the component autonomous activity and the entire swarm can be abstracted away as a piecewise deterministic Markov process, which constitutes one of the most popular model in stochastic control. Keywords: ultra large multi-agent systems, system of systems, autonomous systems, stochastic hybrid systems.

Biomolecular detection using a metal semiconductor field effect transistor

Science.gov (United States)

Estephan, Elias; Saab, Marie-Belle; Buzatu, Petre; Aulombard, Roger; Cuisinier, Frédéric J. G.; Gergely, Csilla; Cloitre, Thierry

2010-04-01

In this work, our attention was drawn towards developing affinity-based electrical biosensors, using a MESFET (Metal Semiconductor Field Effect Transistor). Semiconductor (SC) surfaces must be prepared before the incubations with biomolecules. The peptides route was adapted to exceed and bypass the limits revealed by other types of surface modification due to the unwanted unspecific interactions. As these peptides reveal specific recognition of materials, then controlled functionalization can be achieved. Peptides were produced by phage display technology using a library of M13 bacteriophage. After several rounds of bio-panning, the phages presenting affinities for GaAs SC were isolated; the DNA of these specific phages were sequenced, and the peptide with the highest affinity was synthesized and biotinylated. To explore the possibility of electrical detection, the MESFET fabricated with the GaAs SC were used to detect the streptavidin via the biotinylated peptide in the presence of the bovine Serum Albumin. After each surface modification step, the IDS (current between the drain and the source) of the transistor was measured and a decrease in the intensity was detected. Furthermore, fluorescent microscopy was used in order to prove the specificity of this peptide and the specific localisation of biomolecules. In conclusion, the feasibility of producing an electrical biosensor using a MESFET has been demonstrated. Controlled placement, specific localization and detection of biomolecules on a MESFET transistor were achieved without covering the drain and the source. This method of functionalization and detection can be of great utility for biosensing application opening a new way for developing bioFETs (Biomolecular Field-Effect Transistor).

Stability and Control of Large-Scale Dynamical Systems A Vector Dissipative Systems Approach

CERN Document Server

Haddad, Wassim M

2011-01-01

Modern complex large-scale dynamical systems exist in virtually every aspect of science and engineering, and are associated with a wide variety of physical, technological, environmental, and social phenomena, including aerospace, power, communications, and network systems, to name just a few. This book develops a general stability analysis and control design framework for nonlinear large-scale interconnected dynamical systems, and presents the most complete treatment on vector Lyapunov function methods, vector dissipativity theory, and decentralized control architectures. Large-scale dynami

Balancing modern Power System with large scale of wind power

DEFF Research Database (Denmark)

Basit, Abdul; Altin, Müfit; Hansen, Anca Daniela

2014-01-01

Power system operators must ensure robust, secure and reliable power system operation even with a large scale integration of wind power. Electricity generated from the intermittent wind in large propor-tion may impact on the control of power system balance and thus deviations in the power system...... frequency in small or islanded power systems or tie line power flows in interconnected power systems. Therefore, the large scale integration of wind power into the power system strongly concerns the secure and stable grid operation. To ensure the stable power system operation, the evolving power system has...... to be analysed with improved analytical tools and techniques. This paper proposes techniques for the active power balance control in future power systems with the large scale wind power integration, where power balancing model provides the hour-ahead dispatch plan with reduced planning horizon and the real time...

Tools for the automation of large control systems

CERN Document Server

Gaspar, Clara

2005-01-01

The new LHC experiments at CERN will have very large numbers of channels to operate. In order to be able to configure and monitor such large systems, a high degree of parallelism is necessary. The control system is built as a hierarchy of sub-systems distributed over several computers. A toolkit – SMI++, combining two approaches: finite state machines and rule-based programming, allows for the description of the various sub-systems as decentralized deciding entities, reacting in real-time to changes in the system, thus providing for the automation of standard procedures and the for the automatic recovery from error conditions in a hierarchical fashion. In this paper we will describe the principles and features of SMI++ as well as its integration with an industrial SCADA tool for use by the LHC experiments and we will try to show that such tools, can provide a very convenient mechanism for the automation of large scale, high complexity, applications.

A unified framework for unraveling the functional interaction structure of a biomolecular network based on stimulus-response experimental data.

Science.gov (United States)

Cho, Kwang-Hyun; Choo, Sang-Mok; Wellstead, Peter; Wolkenhauer, Olaf

2005-08-15

We propose a unified framework for the identification of functional interaction structures of biomolecular networks in a way that leads to a new experimental design procedure. In developing our approach, we have built upon previous work. Thus we begin by pointing out some of the restrictions associated with existing structure identification methods and point out how these restrictions may be eased. In particular, existing methods use specific forms of experimental algebraic equations with which to identify the functional interaction structure of a biomolecular network. In our work, we employ an extended form of these experimental algebraic equations which, while retaining their merits, also overcome some of their disadvantages. Experimental data are required in order to estimate the coefficients of the experimental algebraic equation set associated with the structure identification task. However, experimentalists are rarely provided with guidance on which parameters to perturb, and to what extent, to perturb them. When a model of network dynamics is required then there is also the vexed question of sample rate and sample time selection to be resolved. Supplying some answers to these questions is the main motivation of this paper. The approach is based on stationary and/or temporal data obtained from parameter perturbations, and unifies the previous approaches of Kholodenko et al. (PNAS 99 (2002) 12841-12846) and Sontag et al. (Bioinformatics 20 (2004) 1877-1886). By way of demonstration, we apply our unified approach to a network model which cannot be properly identified by existing methods. Finally, we propose an experiment design methodology, which is not limited by the amount of parameter perturbations, and illustrate its use with an in numero example.

Predictive hypotheses are ineffectual in resolving complex biochemical systems.

Science.gov (United States)

Fry, Michael

2018-03-20

Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin-proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential.

Performance Health Monitoring of Large-Scale Systems

Energy Technology Data Exchange (ETDEWEB)

Rajamony, Ram [IBM Research, Austin, TX (United States)

2014-11-20

This report details the progress made on the ASCR funded project Performance Health Monitoring for Large Scale Systems. A large-­scale application may not achieve its full performance potential due to degraded performance of even a single subsystem. Detecting performance faults, isolating them, and taking remedial action is critical for the scale of systems on the horizon. PHM aims to develop techniques and tools that can be used to identify and mitigate such performance problems. We accomplish this through two main aspects. The PHM framework encompasses diagnostics, system monitoring, fault isolation, and performance evaluation capabilities that indicates when a performance fault has been detected, either due to an anomaly present in the system itself or due to contention for shared resources between concurrently executing jobs. Software components called the PHM Control system then build upon the capabilities provided by the PHM framework to mitigate degradation caused by performance problems.

Design techniques for large scale linear measurement systems

International Nuclear Information System (INIS)

Candy, J.V.

1979-03-01

Techniques to design measurement schemes for systems modeled by large scale linear time invariant systems, i.e., physical systems modeled by a large number (> 5) of ordinary differential equations, are described. The techniques are based on transforming the physical system model to a coordinate system facilitating the design and then transforming back to the original coordinates. An example of a three-stage, four-species, extraction column used in the reprocessing of spent nuclear fuel elements is presented. The basic ideas are briefly discussed in the case of noisy measurements. An example using a plutonium nitrate storage vessel (reprocessing) with measurement uncertainty is also presented

Stability of large scale interconnected dynamical systems

International Nuclear Information System (INIS)

Akpan, E.P.

1993-07-01

Large scale systems modelled by a system of ordinary differential equations are considered and necessary and sufficient conditions are obtained for the uniform asymptotic connective stability of the systems using the method of cone-valued Lyapunov functions. It is shown that this model significantly improves the existing models. (author). 9 refs

ECOMICS: a web-based toolkit for investigating the biomolecular web in ecosystems using a trans-omics approach.

Directory of Open Access Journals (Sweden)

Yoshiyuki Ogata

Full Text Available Ecosystems can be conceptually thought of as interconnected environmental and metabolic systems, in which small molecules to macro-molecules interact through diverse networks. State-of-the-art technologies in post-genomic science offer ways to inspect and analyze this biomolecular web using omics-based approaches. Exploring useful genes and enzymes, as well as biomass resources responsible for anabolism and catabolism within ecosystems will contribute to a better understanding of environmental functions and their application to biotechnology. Here we present ECOMICS, a suite of web-based tools for ECosystem trans-OMICS investigation that target metagenomic, metatranscriptomic, and meta-metabolomic systems, including biomacromolecular mixtures derived from biomass. ECOMICS is made of four integrated webtools. E-class allows for the sequence-based taxonomic classification of eukaryotic and prokaryotic ribosomal data and the functional classification of selected enzymes. FT2B allows for the digital processing of NMR spectra for downstream metabolic or chemical phenotyping. Bm-Char allows for statistical assignment of specific compounds found in lignocellulose-based biomass, and HetMap is a data matrix generator and correlation calculator that can be applied to trans-omics datasets as analyzed by these and other web tools. This web suite is unique in that it allows for the monitoring of biomass metabolism in a particular environment, i.e., from macromolecular complexes (FT2DB and Bm-Char to microbial composition and degradation (E-class, and makes possible the understanding of relationships between molecular and microbial elements (HetMap. This website is available to the public domain at: https://database.riken.jp/ecomics/.

Spin valve sensor for biomolecular identification: Design, fabrication, and characterization

Science.gov (United States)

Li, Guanxiong

Biomolecular identification, e.g., DNA recognition, has broad applications in biology and medicine such as gene expression analysis, disease diagnosis, and DNA fingerprinting. Therefore, we have been developing a magnetic biodetection technology based on giant magnetoresistive spin valve sensors and magnetic nanoparticle (developed for the magnetic nanoparticle detection, assuming the equivalent average field of magnetic nanoparticles and the coherent rotation of spin valve free layer magnetization. Micromagnetic simulations have also been performed for the spin valve sensors. The analytical model and micromagnetic simulations are found consistent with each other and are in good agreement with experiments. The prototype spin valve sensors have been fabricated at both micron and submicron scales. We demonstrated the detection of a single 2.8-mum magnetic microbead by micron-sized spin valve sensors. Based on polymer-mediated self-assembly and fine lithography, a bilayer lift-off process was developed to deposit magnetic nanoparticles onto the sensor surface in a controlled manner. With the lift-off deposition method, we have successfully demonstrated the room temperature detection of monodisperse 16-nm Fe3O 4 nanoparticles in a quantity from a few tens to several hundreds by submicron spin valve sensors, proving the feasibility of the nanoparticle detection. As desired for quantitative biodetection, a fairly linear dependence of sensor signal on the number of nanoparticles has been confirmed. The initial detection of DNA hybridization events labeled by magnetic nanoparticles further proved the magnetic biodetection concept.

Large area high-speed metrology SPM system

International Nuclear Information System (INIS)

Klapetek, P; Valtr, M; Martinek, J; Picco, L; Payton, O D; Miles, M; Yacoot, A

2015-01-01

We present a large area high-speed measuring system capable of rapidly generating nanometre resolution scanning probe microscopy data over mm 2 regions. The system combines a slow moving but accurate large area XYZ scanner with a very fast but less accurate small area XY scanner. This arrangement enables very large areas to be scanned by stitching together the small, rapidly acquired, images from the fast XY scanner while simultaneously moving the slow XYZ scanner across the region of interest. In order to successfully merge the image sequences together two software approaches for calibrating the data from the fast scanner are described. The first utilizes the low uncertainty interferometric sensors of the XYZ scanner while the second implements a genetic algorithm with multiple parameter fitting during the data merging step of the image stitching process. The basic uncertainty components related to these high-speed measurements are also discussed. Both techniques are shown to successfully enable high-resolution, large area images to be generated at least an order of magnitude faster than with a conventional atomic force microscope. (paper)

Large area high-speed metrology SPM system

Science.gov (United States)

Klapetek, P.; Valtr, M.; Picco, L.; Payton, O. D.; Martinek, J.; Yacoot, A.; Miles, M.

2015-02-01

We present a large area high-speed measuring system capable of rapidly generating nanometre resolution scanning probe microscopy data over mm2 regions. The system combines a slow moving but accurate large area XYZ scanner with a very fast but less accurate small area XY scanner. This arrangement enables very large areas to be scanned by stitching together the small, rapidly acquired, images from the fast XY scanner while simultaneously moving the slow XYZ scanner across the region of interest. In order to successfully merge the image sequences together two software approaches for calibrating the data from the fast scanner are described. The first utilizes the low uncertainty interferometric sensors of the XYZ scanner while the second implements a genetic algorithm with multiple parameter fitting during the data merging step of the image stitching process. The basic uncertainty components related to these high-speed measurements are also discussed. Both techniques are shown to successfully enable high-resolution, large area images to be generated at least an order of magnitude faster than with a conventional atomic force microscope.

Engineering large-scale agent-based systems with consensus

Science.gov (United States)

Bokma, A.; Slade, A.; Kerridge, S.; Johnson, K.

1994-01-01

The paper presents the consensus method for the development of large-scale agent-based systems. Systems can be developed as networks of knowledge based agents (KBA) which engage in a collaborative problem solving effort. The method provides a comprehensive and integrated approach to the development of this type of system. This includes a systematic analysis of user requirements as well as a structured approach to generating a system design which exhibits the desired functionality. There is a direct correspondence between system requirements and design components. The benefits of this approach are that requirements are traceable into design components and code thus facilitating verification. The use of the consensus method with two major test applications showed it to be successful and also provided valuable insight into problems typically associated with the development of large systems.

Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Mads S. Bergholt

2017-12-01

Full Text Available Analyzing lipid composition and distribution within the brain is important to study white matter pathologies that present focal demyelination lesions, such as multiple sclerosis. Some lesions can endogenously re-form myelin sheaths. Therapies aim to enhance this repair process in order to reduce neurodegeneration and disability progression in patients. In this context, a lipidomic analysis providing both precise molecular classification and well-defined localization is crucial to detect changes in myelin lipid content. Here we develop a correlated heterospectral lipidomic (HSL approach based on coregistered Raman spectroscopy, desorption electrospray ionization mass spectrometry (DESI-MS, and immunofluorescence imaging. We employ HSL to study the structural and compositional lipid profile of demyelination and remyelination in an induced focal demyelination mouse model and in multiple sclerosis lesions from patients ex vivo. Pixelwise coregistration of Raman spectroscopy and DESI-MS imaging generated a heterospectral map used to interrelate biomolecular structure and composition of myelin. Multivariate regression analysis enabled Raman-based assessment of highly specific lipid subtypes in complex tissue for the first time. This method revealed the temporal dynamics of remyelination and provided the first indication that newly formed myelin has a different lipid composition compared to normal myelin. HSL enables detailed molecular myelin characterization that can substantially improve upon the current understanding of remyelination in multiple sclerosis and provides a strategy to assess remyelination treatments in animal models.

Charge patterns as templates for the assembly of layered biomolecular structures.

Science.gov (United States)

Naujoks, Nicola; Stemmer, Andreas

2006-08-01

Electric fields are used to guide the assembly of biomolecules in predefined geometric patterns on solid substrates. Local surface charges serve as templates to selectively position proteins on thin-film polymeric electret layers, thereby creating a basis for site-directed layered assembly of biomolecular structures. Charge patterns are created using the lithographic capabilities of an atomic force microscope, namely by applying voltage pulses between a conductive tip and the sample. Samples consist of a poly(methyl methacrylate) layer on a p-doped silicon support. Subsequently, the sample is developed in a water-in-oil emulsion, consisting of a dispersed aqueous phase containing biotin-modified immunoglobulinG molecules, and a continuous nonpolar, insulating oil phase. The electrostatic fields cause a net force of (di)electrophoretic nature on the droplet, thereby guiding the proteins to the predefined locations. Due to the functionalization of the immunoglobulinG molecules with biotin-groups, these patterns can now be used to initiate the localized layer-by-layer assembly of biomolecules based on the avidin-biotin mechanism. By binding 40 nm sized biotin-labelled beads to the predefined locations via a streptavidin linker, we verify the functionality of the previously deposited immunoglobulinG-biotin. All assembly steps following the initial deposition of the immunoglobulinG from emulsion can conveniently be conducted in aqueous solutions. Results show that pattern definition is maintained after immersion into aqueous solution.

Using Agent Base Models to Optimize Large Scale Network for Large System Inventories

Science.gov (United States)

Shameldin, Ramez Ahmed; Bowling, Shannon R.

2010-01-01

The aim of this paper is to use Agent Base Models (ABM) to optimize large scale network handling capabilities for large system inventories and to implement strategies for the purpose of reducing capital expenses. The models used in this paper either use computational algorithms or procedure implementations developed by Matlab to simulate agent based models in a principal programming language and mathematical theory using clusters, these clusters work as a high performance computational performance to run the program in parallel computational. In both cases, a model is defined as compilation of a set of structures and processes assumed to underlie the behavior of a network system.

Proceedings of the 2nd international advisory committee on biomolecular dynamics instrument DNA in MLF at J-PARC

International Nuclear Information System (INIS)

Arai, Masatoshi; Aizawa, Kazuya; Nakajima, Kenji; Shibata, Kaoru; Takahashi, Nobuaki

2009-07-01

The 2nd International Advisory Committee on the 'Biomolecular Dynamics Backscattering Spectrometer DNA' was held on November 12th - 13th, 2008 at J-PARC Center, Japan Atomic Energy Agency. This IAC has been organized for aiming to realize an innovative neutron backscattering instrument in the Materials and Life Science Experimental Facility (MLF) at the J-PARC and therefore four leading scientists in the field of neutron backscattering instruments has been selected as the member (Dr. Dan Neumann (Chair); Prof. Ferenc Mezei; Dr. Hannu Mutka; Dr. Philip Tregenna-Piggott), and the 1st IAC had been held on February 27th - 29th, 2008. This report includes the executive summary and materials of the presentations in the 2nd IAC. (author)

Sequential decoders for large MIMO systems

KAUST Repository

Ali, Konpal S.; Abediseid, Walid; Alouini, Mohamed-Slim

2014-01-01

the Sequential Decoder using the Fano Algorithm for large MIMO systems. A parameter called the bias is varied to attain different performance-complexity trade-offs. Low values of the bias result in excellent performance but at the expense of high complexity

Models for large superconducting toroidal magnet systems

International Nuclear Information System (INIS)

Arendt, F.; Brechna, H.; Erb, J.; Komarek, P.; Krauth, H.; Maurer, W.

1976-01-01

Prior to the design of large GJ toroidal magnet systems it is appropriate to procure small scale models, which can simulate their pertinent properties and allow to investigate their relevant phenomena. The important feature of the model is to show under which circumstances the system performance can be extrapolated to large magnets. Based on parameters such as the maximum magnetic field and the current density, the maximum tolerable magneto-mechanical stresses, a simple method of designing model magnets is presented. It is shown how pertinent design parameters are changed when the toroidal dimensions are altered. In addition some conductor cost estimations are given based on reactor power output and wall loading

Field-effect sensors - from pH sensing to biosensing: sensitivity enhancement using streptavidin-biotin as a model system.

Science.gov (United States)

Lowe, Benjamin M; Sun, Kai; Zeimpekis, Ioannis; Skylaris, Chris-Kriton; Green, Nicolas G

2017-11-06

Field-Effect Transistor sensors (FET-sensors) have been receiving increasing attention for biomolecular sensing over the last two decades due to their potential for ultra-high sensitivity sensing, label-free operation, cost reduction and miniaturisation. Whilst the commercial application of FET-sensors in pH sensing has been realised, their commercial application in biomolecular sensing (termed BioFETs) is hindered by poor understanding of how to optimise device design for highly reproducible operation and high sensitivity. In part, these problems stem from the highly interdisciplinary nature of the problems encountered in this field, in which knowledge of biomolecular-binding kinetics, surface chemistry, electrical double layer physics and electrical engineering is required. In this work, a quantitative analysis and critical review has been performed comparing literature FET-sensor data for pH-sensing with data for sensing of biomolecular streptavidin binding to surface-bound biotin systems. The aim is to provide the first systematic, quantitative comparison of BioFET results for a single biomolecular analyte, specifically streptavidin, which is the most commonly used model protein in biosensing experiments, and often used as an initial proof-of-concept for new biosensor designs. This novel quantitative and comparative analysis of the surface potential behaviour of a range of devices demonstrated a strong contrast between the trends observed in pH-sensing and those in biomolecule-sensing. Potential explanations are discussed in detail and surface-chemistry optimisation is shown to be a vital component in sensitivity-enhancement. Factors which can influence the response, yet which have not always been fully appreciated, are explored and practical suggestions are provided on how to improve experimental design.

Program system RALLY - for probabilistic safety analysis of large technical systems

International Nuclear Information System (INIS)

Gueldner, W.; Polke, H.; Spindler, H.; Zipf, G.

1982-03-01

This report describes the program system RALLY to compute the reliability of large and intermeshed technical systems. In addition to a short explanation of the different programs, the possible applications of the program system RALLY are demonstrated. Finally, the most important studies carried out so far on RALLY are discussed. (orig.) [de

Large Scale GW Calculations on the Cori System

Science.gov (United States)

Deslippe, Jack; Del Ben, Mauro; da Jornada, Felipe; Canning, Andrew; Louie, Steven

The NERSC Cori system, powered by 9000+ Intel Xeon-Phi processors, represents one of the largest HPC systems for open-science in the United States and the world. We discuss the optimization of the GW methodology for this system, including both node level and system-scale optimizations. We highlight multiple large scale (thousands of atoms) case studies and discuss both absolute application performance and comparison to calculations on more traditional HPC architectures. We find that the GW method is particularly well suited for many-core architectures due to the ability to exploit a large amount of parallelism across many layers of the system. This work was supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Materials Sciences and Engineering Division, as part of the Computational Materials Sciences Program.

High-Throughput, Protein-Targeted Biomolecular Detection Using Frequency-Domain Faraday Rotation Spectroscopy.

Science.gov (United States)

Murdock, Richard J; Putnam, Shawn A; Das, Soumen; Gupta, Ankur; Chase, Elyse D Z; Seal, Sudipta

2017-03-01

A clinically relevant magneto-optical technique (fd-FRS, frequency-domain Faraday rotation spectroscopy) for characterizing proteins using antibody-functionalized magnetic nanoparticles (MNPs) is demonstrated. This technique distinguishes between the Faraday rotation of the solvent, iron oxide core, and functionalization layers of polyethylene glycol polymers (spacer) and model antibody-antigen complexes (anti-BSA/BSA, bovine serum albumin). A detection sensitivity of ≈10 pg mL -1 and broad detection range of 10 pg mL -1 ≲ c BSA ≲ 100 µg mL -1 are observed. Combining this technique with predictive analyte binding models quantifies (within an order of magnitude) the number of active binding sites on functionalized MNPs. Comparative enzyme-linked immunosorbent assay (ELISA) studies are conducted, reproducing the manufacturer advertised BSA ELISA detection limits from 1 ng mL -1 ≲ c BSA ≲ 500 ng mL -1 . In addition to the increased sensitivity, broader detection range, and similar specificity, fd-FRS can be conducted in less than ≈30 min, compared to ≈4 h with ELISA. Thus, fd-FRS is shown to be a sensitive optical technique with potential to become an efficient diagnostic in the chemical and biomolecular sciences. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Martini Coarse-Grained Force Field

NARCIS (Netherlands)

Periole, X.; Marrink, S.J.; Monticelli, Luca; Salonen, Emppu

2013-01-01

The Martini force field is a coarse-grained force field suited for molecular dynamics simulations of biomolecular systems. The force field has been parameterized in a systematic way, based on the reproduction of partitioning free energies between polar and apolar phases of a large number of chemical

Optimization of MIMO Systems Capacity Using Large Random Matrix Methods

Directory of Open Access Journals (Sweden)

Philippe Loubaton

2012-11-01

Full Text Available This paper provides a comprehensive introduction of large random matrix methods for input covariance matrix optimization of mutual information of MIMO systems. It is first recalled informally how large system approximations of mutual information can be derived. Then, the optimization of the approximations is discussed, and important methodological points that are not necessarily covered by the existing literature are addressed, including the strict concavity of the approximation, the structure of the argument of its maximum, the accuracy of the large system approach with regard to the number of antennas, or the justification of iterative water-filling optimization algorithms. While the existing papers have developed methods adapted to a specific model, this contribution tries to provide a unified view of the large system approximation approach.

A coarse-grained model for the simulations of biomolecular interactions in cellular environments

International Nuclear Information System (INIS)

Xie, Zhong-Ru; Chen, Jiawen; Wu, Yinghao

2014-01-01

The interactions of bio-molecules constitute the key steps of cellular functions. However, in vivo binding properties differ significantly from their in vitro measurements due to the heterogeneity of cellular environments. Here we introduce a coarse-grained model based on rigid-body representation to study how factors such as cellular crowding and membrane confinement affect molecular binding. The macroscopic parameters such as the equilibrium constant and the kinetic rate constant are calibrated by adjusting the microscopic coefficients used in the numerical simulations. By changing these model parameters that are experimentally approachable, we are able to study the kinetic and thermodynamic properties of molecular binding, as well as the effects caused by specific cellular environments. We investigate the volumetric effects of crowded intracellular space on bio-molecular diffusion and diffusion-limited reactions. Furthermore, the binding constants of membrane proteins are currently difficult to measure. We provide quantitative estimations about how the binding of membrane proteins deviates from soluble proteins under different degrees of membrane confinements. The simulation results provide biological insights to the functions of membrane receptors on cell surfaces. Overall, our studies establish a connection between the details of molecular interactions and the heterogeneity of cellular environments

Simulation of FRET dyes allows quantitative comparison against experimental data

Science.gov (United States)

Reinartz, Ines; Sinner, Claude; Nettels, Daniel; Stucki-Buchli, Brigitte; Stockmar, Florian; Panek, Pawel T.; Jacob, Christoph R.; Nienhaus, Gerd Ulrich; Schuler, Benjamin; Schug, Alexander

2018-03-01

Fully understanding biomolecular function requires detailed insight into the systems' structural dynamics. Powerful experimental techniques such as single molecule Förster Resonance Energy Transfer (FRET) provide access to such dynamic information yet have to be carefully interpreted. Molecular simulations can complement these experiments but typically face limits in accessing slow time scales and large or unstructured systems. Here, we introduce a coarse-grained simulation technique that tackles these challenges. While requiring only few parameters, we maintain full protein flexibility and include all heavy atoms of proteins, linkers, and dyes. We are able to sufficiently reduce computational demands to simulate large or heterogeneous structural dynamics and ensembles on slow time scales found in, e.g., protein folding. The simulations allow for calculating FRET efficiencies which quantitatively agree with experimentally determined values. By providing atomically resolved trajectories, this work supports the planning and microscopic interpretation of experiments. Overall, these results highlight how simulations and experiments can complement each other leading to new insights into biomolecular dynamics and function.

Soft Supercharging of Biomolecular Ions in Electrospray Ionization Mass Spectrometry

Science.gov (United States)

Chingin, Konstantin; Xu, Ning; Chen, Huanwen

2014-06-01

The charge states of biomolecular ions in ESI-MS can be significantly increased by the addition of low-vapor supercharging (SC) reagents into the spraying solution. Despite the considerable interest from the community, the mechanistic aspects of SC are not well understood and are hotly debated. Arguments that denaturation accounts for the increased charging observed in proteins sprayed from aqueous solutions containing SC reagent have been published widely, but often with incomplete or ambiguous supporting data. In this work, we explored ESI MS charging and SC behavior of several biopolymers including proteins and DNA oligonucleotides. Analytes were ionized from 100 mM ammonium acetate (NH4Ac) aqueous buffer in both positive (ESI+) and negative (ESI-) ion modes. SC was induced either with m-NBA or by the elevated temperature of ESI capillary. For all the analytes studied we, found striking differences in the ESI MS response to these two modes of activation. The data suggest that activation with m-NBA results in more extensive analyte charging with lower degree of denaturation. When working solution with m-NBA was analyzed at elevated temperatures, the SC effect from m-NBA was neutralized. Instead, the net SC effect was similar to the SC effect achieved by thermal activation only. Overall, our observations indicate that SC reagents enhance ESI charging of biomolecules via distinctly different mechanism compared with the traditional approaches based on analyte denaturation. Instead, the data support the hypothesis that the SC phenomenon involves a direct interaction between a biopolymer and SC reagent occurring in evaporating ESI droplets.

Detector correction in large container inspection systems

CERN Document Server

Kang Ke Jun; Chen Zhi Qiang

2002-01-01

In large container inspection systems, the image is constructed by parallel scanning with a one-dimensional detector array with a linac used as the X-ray source. The linear nonuniformity and nonlinearity of multiple detectors and the nonuniform intensity distribution of the X-ray sector beam result in horizontal striations in the scan image. This greatly impairs the image quality, so the image needs to be corrected. The correction parameters are determined experimentally by scaling the detector responses at multiple points with logarithm interpolation of the results. The horizontal striations are eliminated by modifying the original image data with the correction parameters. This method has proven to be effective and applicable in large container inspection systems

Tools for the Automation of Large Distributed Control Systems

CERN Document Server

Gaspar, Clara

2005-01-01

The new LHC experiments at CERN will have very large numbers of channels to operate. In order to be able to configure and monitor such large systems, a high degree of parallelism is necessary. The control system is built as a hierarchy of sub-systems distributed over several computers. A toolkit - SMI++, combining two approaches: finite state machines and rule-based programming, allows for the description of the various sub-systems as decentralized deciding entities, reacting is real-time to changes in the system, thus providing for the automation of standard procedures and for the automatic recovery from error conditions in a hierarchical fashion. In this paper we will describe the principles and features of SMI++ as well as its integration with an industrial SCADA tool for use by the LHC experiments and we will try to show that such tools, can provide a very convenient mechanism for the automation of large scale, high complexity, applications.

The laboratory technology of discrete molecular separation: the historical development of gel electrophoresis and the material epistemology of biomolecular science, 1945-1970.

Science.gov (United States)

Chiang, Howard Hsueh-hao

2009-01-01

Preparative and analytical methods developed by separation scientists have played an important role in the history of molecular biology. One such early method is gel electrophoresis, a technique that uses various types of gel as its supporting medium to separate charged molecules based on size and other properties. Historians of science, however, have only recently begun to pay closer attention to this material epistemological dimension of biomolecular science. This paper substantiates the historiographical thread that explores the relationship between modern laboratory practice and the production of scientific knowledge. It traces the historical development of gel electrophoresis from the mid-1940s to the mid-1960s, with careful attention to the interplay between technical developments and disciplinary shifts, especially the rise of molecular biology in this time-frame. Claiming that the early 1950s marked a decisive shift in the evolution of electrophoretic methods from moving boundary to zone electrophoresis, I reconstruct various trajectories in which scientists such as Oliver Smithies sought out the most desirable solid supporting medium for electrophoretic instrumentation. Biomolecular knowledge, I argue, emerged in part from this process of seeking the most appropriate supporting medium that allowed for discrete molecular separation and visualization. The early 1950s, therefore, marked not only an important turning point in the history of separation science, but also a transformative moment in the history of the life sciences as the growth of molecular biology depended in part on the epistemological access to the molecular realm available through these evolving technologies.

Constructing Optimal Coarse-Grained Sites of Huge Biomolecules by Fluctuation Maximization.

Science.gov (United States)

Li, Min; Zhang, John Zenghui; Xia, Fei

2016-04-12

Coarse-grained (CG) models are valuable tools for the study of functions of large biomolecules on large length and time scales. The definition of CG representations for huge biomolecules is always a formidable challenge. In this work, we propose a new method called fluctuation maximization coarse-graining (FM-CG) to construct the CG sites of biomolecules. The defined residual in FM-CG converges to a maximal value as the number of CG sites increases, allowing an optimal CG model to be rigorously defined on the basis of the maximum. More importantly, we developed a robust algorithm called stepwise local iterative optimization (SLIO) to accelerate the process of coarse-graining large biomolecules. By means of the efficient SLIO algorithm, the computational cost of coarse-graining large biomolecules is reduced to within the time scale of seconds, which is far lower than that of conventional simulated annealing. The coarse-graining of two huge systems, chaperonin GroEL and lengsin, indicates that our new methods can coarse-grain huge biomolecular systems with up to 10,000 residues within the time scale of minutes. The further parametrization of CG sites derived from FM-CG allows us to construct the corresponding CG models for studies of the functions of huge biomolecular systems.

Quality Function Deployment for Large Systems

Science.gov (United States)

Dean, Edwin B.

1992-01-01

Quality Function Deployment (QFD) is typically applied to small subsystems. This paper describes efforts to extend QFD to large scale systems. It links QFD to the system engineering process, the concurrent engineering process, the robust design process, and the costing process. The effect is to generate a tightly linked project management process of high dimensionality which flushes out issues early to provide a high quality, low cost, and, hence, competitive product. A pre-QFD matrix linking customers to customer desires is described.

An automated system designed for large scale NMR data deposition and annotation: application to over 600 assigned chemical shift data entries to the BioMagResBank from the Riken Structural Genomics/Proteomics Initiative internal database

International Nuclear Information System (INIS)

Kobayashi, Naohiro; Harano, Yoko; Tochio, Naoya; Nakatani, Eiichi; Kigawa, Takanori; Yokoyama, Shigeyuki; Mading, Steve; Ulrich, Eldon L.; Markley, John L.; Akutsu, Hideo; Fujiwara, Toshimichi

2012-01-01

Biomolecular NMR chemical shift data are key information for the functional analysis of biomolecules and the development of new techniques for NMR studies utilizing chemical shift statistical information. Structural genomics projects are major contributors to the accumulation of protein chemical shift information. The management of the large quantities of NMR data generated by each project in a local database and the transfer of the data to the public databases are still formidable tasks because of the complicated nature of NMR data. Here we report an automated and efficient system developed for the deposition and annotation of a large number of data sets including 1 H, 13 C and 15 N resonance assignments used for the structure determination of proteins. We have demonstrated the feasibility of our system by applying it to over 600 entries from the internal database generated by the RIKEN Structural Genomics/Proteomics Initiative (RSGI) to the public database, BioMagResBank (BMRB). We have assessed the quality of the deposited chemical shifts by comparing them with those predicted from the PDB coordinate entry for the corresponding protein. The same comparison for other matched BMRB/PDB entries deposited from 2001–2011 has been carried out and the results suggest that the RSGI entries greatly improved the quality of the BMRB database. Since the entries include chemical shifts acquired under strikingly similar experimental conditions, these NMR data can be expected to be a promising resource to improve current technologies as well as to develop new NMR methods for protein studies.

Hydrothermal processes above the Yellowstone magma chamber: Large hydrothermal systems and large hydrothermal explosions

Science.gov (United States)

Morgan, L.A.; Shanks, W.C. Pat; Pierce, K.L.

2009-01-01

and vein-fi lling; and (5) areal dimensions of many large hydrothermal explosion craters in Yellowstone are similar to those of its active geyser basins and thermal areas. For Yellowstone, our knowledge of hydrothermal craters and ejecta is generally limited to after the Yellowstone Plateau emerged from beneath a late Pleistocene icecap that was roughly a kilometer thick. Large hydrothermal explosions may have occurred earlier as indicated by multiple episodes of cementation and brecciation commonly observed in hydrothermal ejecta clasts. Critical components for large, explosive hydrothermal systems include a watersaturated system at or near boiling temperatures and an interconnected system of well-developed joints and fractures along which hydrothermal fluids flow. Active deformation of the Yellowstone caldera, active faulting and moderate local seismicity, high heat flow, rapid changes in climate, and regional stresses are factors that have strong infl uences on the type of hydrothermal system developed. Ascending hydrothermal fluids flow along fractures that have developed in response to active caldera deformation and along edges of low-permeability rhyolitic lava flows. Alteration of the area affected, self-sealing leading to development of a caprock for the hydrothermal system, and dissolution of silica-rich rocks are additional factors that may constrain the distribution and development of hydrothermal fields. A partial lowpermeability layer that acts as a cap to the hydrothermal system may produce some over-pressurization, thought to be small in most systems. Any abrupt drop in pressure initiates steam fl ashing and is rapidly transmitted through interconnected fractures that result in a series of multiple large-scale explosions contributing to the excavation of a larger explosion crater. Similarities between the size and dimensions of large hydrothermal explosion craters and thermal fields in Yellowstone may indicate that catastrophic events which result in l

Challenges in parameter identification of large structural dynamic systems

International Nuclear Information System (INIS)

Koh, C.G.

2001-01-01

In theory, it is possible to determine the parameters of a structural or mechanical system by subjecting it to some dynamic excitation and measuring the response. Considerable research has been carried out in this subject area known as the system identification over the past two decades. Nevertheless, the challenges associated with numerical convergence are still formidable when the system is large in terms of the number of degrees of freedom and number of unknowns. While many methods work for small systems, the convergence becomes difficult, if not impossible, for large systems. In this keynote lecture, both classical and non-classical system identification methods for dynamic testing and vibration-based inspection are discussed. For classical methods, the extended Kalman filter (EKF) approach is used. On this basis, a substructural identification method has been developed as a strategy to deal with large structural systems. This is achieved by reducing the problem size, thereby significantly improving the numerical convergence and efficiency. Two versions of this method are presented each with its own merits. A numerical example of frame structure with 20 unknown parameters is illustrated. For non-classical methods, the Genetic Algorithm (GA) is shown to be applicable with relative ease due to its 'forward analysis' nature. The computational time is, however, still enormous for large structural systems due to the combinatorial explosion problem. A model GA method has been developed to address this problem and tested with considerable success on a relatively large system of 50 degrees of freedom, accounting for input and output noise effects. An advantages of this GA-based identification method is that the objective function can be defined in response measured. Numerical studies show that the method is relatively robust, as it does in response measured. Numerical studies show that the method is relatively robust, as it dos not require good initial guess and the

LARGE-SCALE TOPOLOGICAL PROPERTIES OF MOLECULAR NETWORKS.

Energy Technology Data Exchange (ETDEWEB)

MASLOV,S.SNEPPEN,K.

2003-11-17

Bio-molecular networks lack the top-down design. Instead, selective forces of biological evolution shape them from raw material provided by random events such as gene duplications and single gene mutations. As a result individual connections in these networks are characterized by a large degree of randomness. One may wonder which connectivity patterns are indeed random, while which arose due to the network growth, evolution, and/or its fundamental design principles and limitations? Here we introduce a general method allowing one to construct a random null-model version of a given network while preserving the desired set of its low-level topological features, such as, e.g., the number of neighbors of individual nodes, the average level of modularity, preferential connections between particular groups of nodes, etc. Such a null-model network can then be used to detect and quantify the non-random topological patterns present in large networks. In particular, we measured correlations between degrees of interacting nodes in protein interaction and regulatory networks in yeast. It was found that in both these networks, links between highly connected proteins are systematically suppressed. This effect decreases the likelihood of cross-talk between different functional modules of the cell, and increases the overall robustness of a network by localizing effects of deleterious perturbations. It also teaches us about the overall computational architecture of such networks and points at the origin of large differences in the number of neighbors of individual nodes.

Recovering from trust breakdowns in large system implementations

DEFF Research Database (Denmark)

Rerup Schlichter, Bjarne Rerup; Andersen, Povl Erik Rostgård

2011-01-01

On the basis of experiences from the Faroese large-scale implementation of integrated healthcare information systems and insights into dynamic aspects of trust, we offer the following lessons learned for the successful management and recovery of trust (breakdowns) in large system implementations......: restore relations by turning towards face-to-face events and procedures, assure a well-functioning and available support organization, demonstrate trust in actors to enhance their own self-confidence and celebrate successes, even the smallest or ones injected by yourself. The propositions are based on a 6...

Biomolecular Modeling in a Process Dynamics and Control Course

Science.gov (United States)

Gray, Jeffrey J.

2006-01-01

I present modifications to the traditional course entitled, "Process dynamics and control," which I renamed "Modeling, dynamics, and control of chemical and biological processes." Additions include the central dogma of biology, pharmacokinetic systems, population balances, control of gene transcription, and large­-scale…

On Lattice Sequential Decoding for Large MIMO Systems

KAUST Repository

Ali, Konpal S.

2014-04-01

Due to their ability to provide high data rates, Multiple-Input Multiple-Output (MIMO) wireless communication systems have become increasingly popular. Decoding of these systems with acceptable error performance is computationally very demanding. In the case of large overdetermined MIMO systems, we employ the Sequential Decoder using the Fano Algorithm. A parameter called the bias is varied to attain different performance-complexity trade-offs. Low values of the bias result in excellent performance but at the expense of high complexity and vice versa for higher bias values. We attempt to bound the error by bounding the bias, using the minimum distance of a lattice. Also, a particular trend is observed with increasing SNR: a region of low complexity and high error, followed by a region of high complexity and error falling, and finally a region of low complexity and low error. For lower bias values, the stages of the trend are incurred at lower SNR than for higher bias values. This has the important implication that a low enough bias value, at low to moderate SNR, can result in low error and low complexity even for large MIMO systems. Our work is compared against Lattice Reduction (LR) aided Linear Decoders (LDs). Another impressive observation for low bias values that satisfy the error bound is that the Sequential Decoder\\'s error is seen to fall with increasing system size, while it grows for the LR-aided LDs. For the case of large underdetermined MIMO systems, Sequential Decoding with two preprocessing schemes is proposed – 1) Minimum Mean Square Error Generalized Decision Feedback Equalization (MMSE-GDFE) preprocessing 2) MMSE-GDFE preprocessing, followed by Lattice Reduction and Greedy Ordering. Our work is compared against previous work which employs Sphere Decoding preprocessed using MMSE-GDFE, Lattice Reduction and Greedy Ordering. For the case of large systems, this results in high complexity and difficulty in choosing the sphere radius. Our schemes

Numerical solution of large sparse linear systems

International Nuclear Information System (INIS)

Meurant, Gerard; Golub, Gene.

1982-02-01

This note is based on one of the lectures given at the 1980 CEA-EDF-INRIA Numerical Analysis Summer School whose aim is the study of large sparse linear systems. The main topics are solving least squares problems by orthogonal transformation, fast Poisson solvers and solution of sparse linear system by iterative methods with a special emphasis on preconditioned conjuguate gradient method [fr

Large-Scale Systems Control Design via LMI Optimization

Czech Academy of Sciences Publication Activity Database

Rehák, Branislav

2015-01-01

Roč. 44, č. 3 (2015), s. 247-253 ISSN 1392-124X Institutional support: RVO:67985556 Keywords : Combinatorial linear matrix inequalities * large-scale system * decentralized control Subject RIV: BC - Control Systems Theory Impact factor: 0.633, year: 2015

Protein-Ligand Informatics Force Field (PLIff): Toward a Fully Knowledge Driven "Force Field" for Biomolecular Interactions.

Science.gov (United States)

Verdonk, Marcel L; Ludlow, R Frederick; Giangreco, Ilenia; Rathi, Prakash Chandra

2016-07-28

The Protein Data Bank (PDB) contains a wealth of data on nonbonded biomolecular interactions. If this information could be distilled down to nonbonded interaction potentials, these would have some key advantages over standard force fields. However, there are some important outstanding issues to address in order to do this successfully. This paper introduces the protein-ligand informatics "force field", PLIff, which begins to address these key challenges ( https://bitbucket.org/AstexUK/pli ). As a result of their knowledge-based nature, the next-generation nonbonded potentials that make up PLIff automatically capture a wide range of interaction types, including special interactions that are often poorly described by standard force fields. We illustrate how PLIff may be used in structure-based design applications, including interaction fields, fragment mapping, and protein-ligand docking. PLIff performs at least as well as state-of-the art scoring functions in terms of pose predictions and ranking compounds in a virtual screening context.

Self-* and Adaptive Mechanisms for Large Scale Distributed Systems

Science.gov (United States)

Fragopoulou, P.; Mastroianni, C.; Montero, R.; Andrjezak, A.; Kondo, D.

Large-scale distributed computing systems and infrastructure, such as Grids, P2P systems and desktop Grid platforms, are decentralized, pervasive, and composed of a large number of autonomous entities. The complexity of these systems is such that human administration is nearly impossible and centralized or hierarchical control is highly inefficient. These systems need to run on highly dynamic environments, where content, network topologies and workloads are continuously changing. Moreover, they are characterized by the high degree of volatility of their components and the need to provide efficient service management and to handle efficiently large amounts of data. This paper describes some of the areas for which adaptation emerges as a key feature, namely, the management of computational Grids, the self-management of desktop Grid platforms and the monitoring and healing of complex applications. It also elaborates on the use of bio-inspired algorithms to achieve self-management. Related future trends and challenges are described.

A Chain Perspective on Large-scale Number Systems

NARCIS (Netherlands)

Grijpink, J.H.A.M.

2012-01-01

As large-scale number systems gain significance in social and economic life (electronic communication, remote electronic authentication), the correct functioning and the integrity of public number systems take on crucial importance. They are needed to uniquely indicate people, objects or phenomena

Construction of a large laser fusion system

International Nuclear Information System (INIS)

Hurley, C.A.

1977-01-01

Construction of a large laser fusion machine is nearing completion at the Lawrence Livermore Laboratory (LLL). Shiva, a 20-terawatt neodymium doped glass system, will be complete in early 1978. This system will have the high power needed to demonstrate significant thermonuclear burn. Shiva will irradiate a microscopic D-T pellet with 20 separate laser beams arriving simultaneously at the target. This requires precise alignment, and stability to maintain alignment. Hardware for the 20 laser chains is composed of 140 amplifiers, 100 spatial filters, 80 isolation stages, 40 large turning mirrors, and a front-end splitter system of over 100 parts. These are mounted on a high stability, three dimensional spaceframe which serves as an optical bench. The mechanical design effort, spanning approximately 3 years, followed a classic engineering evolution. The conceptual design phase led directly to system optimization through cost and technical tradeoffs. Additional manpower was then required for detailed design and specification of hardware and fabrication. Design of long-lead items was started early in order to initiate fabrication and assembly while the rest of the design was completed. All components were ready for assembly and construction as fiscal priorities and schedules permitted

Radiation damage in biomolecular systems

CERN Document Server

Fuss, Martina Christina

2012-01-01

Since the discovery of X-rays and radioactivity, ionizing radiations have been widely applied in medicine both for diagnostic and therapeutic purposes. The risks associated with radiation exposure and handling led to the parallel development of the field of radiation protection. Pioneering experiments done by Sanche and co-workers in 2000 showed that low-energy secondary electrons, which are abundantly generated along radiation tracks, are primarily responsible for radiation damage through successive interactions with the molecular constituents of the medium. Apart from ionizing processes, which are usually related to radiation damage, below the ionization level low-energy electrons can induce molecular fragmentation via dissociative processes such as internal excitation and electron attachment. This prompted collaborative projects between different research groups from European countries together with other specialists from Canada,  the USA and Australia. This book summarizes the advances achieved by these...

Large-scale modelling of neuronal systems

International Nuclear Information System (INIS)

Castellani, G.; Verondini, E.; Giampieri, E.; Bersani, F.; Remondini, D.; Milanesi, L.; Zironi, I.

2009-01-01

The brain is, without any doubt, the most, complex system of the human body. Its complexity is also due to the extremely high number of neurons, as well as the huge number of synapses connecting them. Each neuron is capable to perform complex tasks, like learning and memorizing a large class of patterns. The simulation of large neuronal systems is challenging for both technological and computational reasons, and can open new perspectives for the comprehension of brain functioning. A well-known and widely accepted model of bidirectional synaptic plasticity, the BCM model, is stated by a differential equation approach based on bistability and selectivity properties. We have modified the BCM model extending it from a single-neuron to a whole-network model. This new model is capable to generate interesting network topologies starting from a small number of local parameters, describing the interaction between incoming and outgoing links from each neuron. We have characterized this model in terms of complex network theory, showing how this, learning rule can be a support For network generation.

Dynamics of Large Systems of Nonlinearly Evolving Units

Science.gov (United States)

Lu, Zhixin

The dynamics of large systems of many nonlinearly evolving units is a general research area that has great importance for many areas in science and technology, including biology, computation by artificial neural networks, statistical mechanics, flocking in animal groups, the dynamics of coupled neurons in the brain, and many others. While universal principles and techniques are largely lacking in this broad area of research, there is still one particular phenomenon that seems to be broadly applicable. In particular, this is the idea of emergence, by which is meant macroscopic behaviors that "emerge" from a large system of many "smaller or simpler entities such that...large entities" [i.e., macroscopic behaviors] arise which "exhibit properties the smaller/simpler entities do not exhibit." In this thesis we investigate mechanisms and manifestations of emergence in four dynamical systems consisting many nonlinearly evolving units. These four systems are as follows. (a) We first study the motion of a large ensemble of many noninteracting particles in a slowly changing Hamiltonian system that undergoes a separatrix crossing. In such systems, we find that separatrix-crossing induces a counterintuitive effect. Specifically, numerical simulation of two sets of densely sprinkled initial conditions on two energy curves appears to suggest that the two energy curves, one originally enclosing the other, seemingly interchange their positions. This, however, is topologically forbidden. We resolve this paradox by introducing a numerical simulation method we call "robust" and study its consequences. (b) We next study the collective dynamics of oscillatory pacemaker neurons in Suprachiasmatic Nucleus (SCN), which, through synchrony, govern the circadian rhythm of mammals. We start from a high-dimensional description of the many coupled oscillatory neuronal units within the SCN. This description is based on a forced Kuramoto model. We then reduce the system dimensionality by using

Large autonomous spacecraft electrical power system (LASEPS)

Science.gov (United States)

Dugal-Whitehead, Norma R.; Johnson, Yvette B.

1992-01-01

NASA - Marshall Space Flight Center is creating a large high voltage electrical power system testbed called LASEPS. This testbed is being developed to simulate an end-to-end power system from power generation and source to loads. When the system is completed it will have several power configurations, which will include several battery configurations. These configurations are: two 120 V batteries, one or two 150 V batteries, and one 250 to 270 V battery. This breadboard encompasses varying levels of autonomy from remote power converters to conventional software control to expert system control of the power system elements. In this paper, the construction and provisions of this breadboard are discussed.

TopologyNet: Topology based deep convolutional and multi-task neural networks for biomolecular property predictions

Science.gov (United States)

2017-01-01

Although deep learning approaches have had tremendous success in image, video and audio processing, computer vision, and speech recognition, their applications to three-dimensional (3D) biomolecular structural data sets have been hindered by the geometric and biological complexity. To address this problem we introduce the element-specific persistent homology (ESPH) method. ESPH represents 3D complex geometry by one-dimensional (1D) topological invariants and retains important biological information via a multichannel image-like representation. This representation reveals hidden structure-function relationships in biomolecules. We further integrate ESPH and deep convolutional neural networks to construct a multichannel topological neural network (TopologyNet) for the predictions of protein-ligand binding affinities and protein stability changes upon mutation. To overcome the deep learning limitations from small and noisy training sets, we propose a multi-task multichannel topological convolutional neural network (MM-TCNN). We demonstrate that TopologyNet outperforms the latest methods in the prediction of protein-ligand binding affinities, mutation induced globular protein folding free energy changes, and mutation induced membrane protein folding free energy changes. Availability: weilab.math.msu.edu/TDL/ PMID:28749969

Effects of Clear Kefir on Biomolecular Aspects of Glycemic Status of Type 2 Diabetes Mellitus (T2DM Patients in Bandung, West Java [Study on Human Blood Glucose, c Peptide and Insulin

Directory of Open Access Journals (Sweden)

Judiono J

2014-08-01

Full Text Available Background: Diabetes Mellitus (DM triggers an excessive reaction of free-radicals. It increases reactive oxygen species and reduces antioxidants status as well as the β cell damage. Clear kefir was used for DM therapies, however it limited biomolecular exploration of its bioactive roles. Research aimed to investigate the effects of clear kefir on the biomolecular nature of the glycemic status of T2DM in Bandung. Methods: The randomized pretest-posttest control group was conducted by 106 T2DM patients. Research was done in several hospitals in Bandung and Cimahi, West Java from 2012–2013. Samples were divided randomly into three groups: (1 T2DM with HbA1c 7 fed standard diet and supplemented 200 ml/day by clear kefir, (3 T2DM with HbA1c was fed a standard diet as a control group. Dose response was obtained from a preeliminary vivo study, and then converted to human dosage by year 2011. Intervention was effectively done for 30 days. HbA1c was measured by HPLC. Fasting blood glucose (FBG and Postprandial blood glucose levels (PBG were measured by enzymes levels. C Peptide and insulin were measured by Elisa. Data was analyzed by a statictics programme by significance p<0,05. Study was approved by ethic committee. Results : HbA1c was significantly reduced in delta level (p<0.01 and FBG (p<0.015 among kefir groups. PBG was not significantly reduced among groups. C-Peptide was significantly increased in delta level, except in control group (p<0.014. Insulin was reduced significantly, except in control group (p<0.003. Conclusions : Supplementation of clear kefir reduced blood glucose levels (HbA1c, FBG, PBG and increased c-peptide. Clear kefir’s biomolecular mechanisms and chemistry characterization is a challenge for future studies.

Large Superconducting Magnet Systems

CERN Document Server

Védrine, P.

2014-07-17

The increase of energy in accelerators over the past decades has led to the design of superconducting magnets for both accelerators and the associated detectors. The use of Nb−Ti superconducting materials allows an increase in the dipole field by up to 10 T compared with the maximum field of 2 T in a conventional magnet. The field bending of the particles in the detectors and generated by the magnets can also be increased. New materials, such as Nb$_{3}$Sn and high temperature superconductor (HTS) conductors, can open the way to higher fields, in the range 13–20 T. The latest generations of fusion machines producing hot plasma also use large superconducting magnet systems.

Large Superconducting Magnet Systems

Energy Technology Data Exchange (ETDEWEB)

Védrine, P [Saclay (France)

2014-07-01

The increase of energy in accelerators over the past decades has led to the design of superconducting magnets for both accelerators and the associated detectors. The use of Nb−Ti superconducting materials allows an increase in the dipole field by up to 10 T compared with the maximum field of 2 T in a conventional magnet. The field bending of the particles in the detectors and generated by the magnets can also be increased. New materials, such as Nb3Sn and high temperature superconductor (HTS) conductors, can open the way to higher fields, in the range 13–20 T. The latest generations of fusion machines producing hot plasma also use large superconducting magnet systems.

An Axiomatic Analysis Approach for Large-Scale Disaster-Tolerant Systems Modeling

Directory of Open Access Journals (Sweden)

Theodore W. Manikas

2011-02-01

Full Text Available Disaster tolerance in computing and communications systems refers to the ability to maintain a degree of functionality throughout the occurrence of a disaster. We accomplish the incorporation of disaster tolerance within a system by simulating various threats to the system operation and identifying areas for system redesign. Unfortunately, extremely large systems are not amenable to comprehensive simulation studies due to the large computational complexity requirements. To address this limitation, an axiomatic approach that decomposes a large-scale system into smaller subsystems is developed that allows the subsystems to be independently modeled. This approach is implemented using a data communications network system example. The results indicate that the decomposition approach produces simulation responses that are similar to the full system approach, but with greatly reduced simulation time.

Market penetration of large wind/diesel systems

International Nuclear Information System (INIS)

Kronborg, T.

1992-01-01

Burmeister ampersand Wain is developing a large size wind/diesel package in collaboration with Micon, the Danish wind turbine manufacturer, and the Danish utility NESA. The package comprises an initial calculation of the technical feasibility and the economic viability of an actual project, installing the optimum number of large wind turbines, and service, operation, and maintenance as needed. The concept should be seen as an addition to existing diesel-based power stations. Wind turbines are especially advantageous in smaller diesel-based electrical systems in the 1-20 MW range because such systems can have high fuel costs and expensive maintenance. Analysis of the market for the wind/diesel concept indicates islands and remote areas with limited population are likely candidates for implementation of wind/diesel systems. An example of an economic analysis of a wind/diesel application on an isolated island is presented, showing the cost savings possible. To obtain practical experience and to demonstrate the wind/diesel concept, a MW-size demonstration plant is being constructed in Denmark

Enzymatic Ligation of Large Biomolecules to DNA

DEFF Research Database (Denmark)

Sørensen, Rasmus Schøler; Okholm, Anders Hauge; Schaffert, David Henning

2013-01-01

The ability to synthesize, characterize, and manipulate DNA forms the foundation of a range of advanced disciplines including genomics, molecular biology, and biomolecular engineering. In particular for the latter field, DNA has proven useful as a structural or functional component in nanoscale s....... As a proof of principle, parallelly labeled oligonucleotides were used to produce nanopatterned DNA origami structures, demonstrating rapid and versatile incorporation of non-DNA components into DNA nanoarchitectures....

Large Coil Program magnetic system design study

International Nuclear Information System (INIS)

Moses, S.D.; Johnson, N.E.

1977-01-01

The primary objective of the Large Coil Program (LCP) is to demonstrate the reliable operation of large superconducting coils to provide a basis for the design principles, materials, and fabrication techniques proposed for the toroidal magnets for the THE NEXT STEP (TNS) and other future tokamak devices. This paper documents a design study of the Large Coil Test Facility (LCTF) in which the structural response of the Toroidal Field (TF) Coils and the supporting structure was evaluated under simulated reactor conditions. The LCP test facility structural system consists of six TF Coils, twelve coil-to-coil torsional restraining beams (torque rings), a central bucking post with base, and a Pulse Coil system. The NASTRAN Finite Element Structural Analysis computer Code was utilized to determine the distribution of deflections, forces, and stresses for each of the TF Coils, torque rings, and the central bucking post. Eleven load conditions were selected to represent probable test operations. Pulse Coils suspended in the bore of the test coil were energized to simulate the pulsed field environment characteristic of the TNS reactor system. The TORMAC Computer Code was utilized to develop the magnetic forces in the TF Coils for each of the eleven loading conditions examined, with or without the Pulse Coils energized. The TORMAC computer program output forces were used directly as input load conditions for the NASTRAN analyses. Results are presented which demonstrate the reliability of the LCTF under simulated reactor operating conditions

Rule-based modeling: a computational approach for studying biomolecular site dynamics in cell signaling systems

Science.gov (United States)

Chylek, Lily A.; Harris, Leonard A.; Tung, Chang-Shung; Faeder, James R.; Lopez, Carlos F.

2013-01-01

Rule-based modeling was developed to address the limitations of traditional approaches for modeling chemical kinetics in cell signaling systems. These systems consist of multiple interacting biomolecules (e.g., proteins), which themselves consist of multiple parts (e.g., domains, linear motifs, and sites of phosphorylation). Consequently, biomolecules that mediate information processing generally have the potential to interact in multiple ways, with the number of possible complexes and post-translational modification states tending to grow exponentially with the number of binary interactions considered. As a result, only large reaction networks capture all possible consequences of the molecular interactions that occur in a cell signaling system, which is problematic because traditional modeling approaches for chemical kinetics (e.g., ordinary differential equations) require explicit network specification. This problem is circumvented through representation of interactions in terms of local rules. With this approach, network specification is implicit and model specification is concise. Concise representation results in a coarse graining of chemical kinetics, which is introduced because all reactions implied by a rule inherit the rate law associated with that rule. Coarse graining can be appropriate if interactions are modular, and the coarseness of a model can be adjusted as needed. Rules can be specified using specialized model-specification languages, and recently developed tools designed for specification of rule-based models allow one to leverage powerful software engineering capabilities. A rule-based model comprises a set of rules, which can be processed by general-purpose simulation and analysis tools to achieve different objectives (e.g., to perform either a deterministic or stochastic simulation). PMID:24123887

Rule-based modeling: a computational approach for studying biomolecular site dynamics in cell signaling systems.

Science.gov (United States)

Chylek, Lily A; Harris, Leonard A; Tung, Chang-Shung; Faeder, James R; Lopez, Carlos F; Hlavacek, William S

2014-01-01

Rule-based modeling was developed to address the limitations of traditional approaches for modeling chemical kinetics in cell signaling systems. These systems consist of multiple interacting biomolecules (e.g., proteins), which themselves consist of multiple parts (e.g., domains, linear motifs, and sites of phosphorylation). Consequently, biomolecules that mediate information processing generally have the potential to interact in multiple ways, with the number of possible complexes and posttranslational modification states tending to grow exponentially with the number of binary interactions considered. As a result, only large reaction networks capture all possible consequences of the molecular interactions that occur in a cell signaling system, which is problematic because traditional modeling approaches for chemical kinetics (e.g., ordinary differential equations) require explicit network specification. This problem is circumvented through representation of interactions in terms of local rules. With this approach, network specification is implicit and model specification is concise. Concise representation results in a coarse graining of chemical kinetics, which is introduced because all reactions implied by a rule inherit the rate law associated with that rule. Coarse graining can be appropriate if interactions are modular, and the coarseness of a model can be adjusted as needed. Rules can be specified using specialized model-specification languages, and recently developed tools designed for specification of rule-based models allow one to leverage powerful software engineering capabilities. A rule-based model comprises a set of rules, which can be processed by general-purpose simulation and analysis tools to achieve different objectives (e.g., to perform either a deterministic or stochastic simulation). © 2013 Wiley Periodicals, Inc.

Geothermal ORC Systems Using Large Screw Expanders

OpenAIRE

Biederman, Tim R.; Brasz, Joost J.

2014-01-01

Geothermal ORC Systems using Large Screw Expanders Tim Biederman Cyrq Energy Abstract This paper describes a low-temperature Organic Rankine Cycle Power Recovery system with a screw expander a derivative of developed of Kaishan's line of screw compressors, as its power unit. The screw expander design is a modified version of its existing refrigeration compressor used on water-cooled chillers. Starting the ORC development program with existing refrigeration screw compre...

Collaboration and Virtualization in Large Information Systems Projects

Directory of Open Access Journals (Sweden)

Stefan Ioan NITCHI

2009-01-01

Full Text Available A project is evolving through different phases from idea and conception until the experiments, implementation and maintenance. The globalization, the Internet, the Web and the mobile computing changed many human activities, and in this respect, the realization of the Information System (IS projects. The projects are growing, the teams are geographically distributed, and the users are heterogeneous. In this respect, the realization of the large Information Technology (IT projects needs to use collaborative technologies. The distribution of the team, the users' heterogeneity and the project complexity determines the virtualization. This paper is an overview of these aspects for large IT projects. It shortly present a general framework developed by the authors for collaborative systems in general and adapted to collaborative project management. The general considerations are illustrated on the case of a large IT project in which the authors were involved.

Engineering management of large scale systems

Science.gov (United States)

Sanders, Serita; Gill, Tepper L.; Paul, Arthur S.

1989-01-01

The organization of high technology and engineering problem solving, has given rise to an emerging concept. Reasoning principles for integrating traditional engineering problem solving with system theory, management sciences, behavioral decision theory, and planning and design approaches can be incorporated into a methodological approach to solving problems with a long range perspective. Long range planning has a great potential to improve productivity by using a systematic and organized approach. Thus, efficiency and cost effectiveness are the driving forces in promoting the organization of engineering problems. Aspects of systems engineering that provide an understanding of management of large scale systems are broadly covered here. Due to the focus and application of research, other significant factors (e.g., human behavior, decision making, etc.) are not emphasized but are considered.

Remote collaboration system based on large scale simulation

International Nuclear Information System (INIS)

Kishimoto, Yasuaki; Sugahara, Akihiro; Li, J.Q.

2008-01-01

Large scale simulation using super-computer, which generally requires long CPU time and produces large amount of data, has been extensively studied as a third pillar in various advanced science fields in parallel to theory and experiment. Such a simulation is expected to lead new scientific discoveries through elucidation of various complex phenomena, which are hardly identified only by conventional theoretical and experimental approaches. In order to assist such large simulation studies for which many collaborators working at geographically different places participate and contribute, we have developed a unique remote collaboration system, referred to as SIMON (simulation monitoring system), which is based on client-server system control introducing an idea of up-date processing, contrary to that of widely used post-processing. As a key ingredient, we have developed a trigger method, which transmits various requests for the up-date processing from the simulation (client) running on a super-computer to a workstation (server). Namely, the simulation running on a super-computer actively controls the timing of up-date processing. The server that has received the requests from the ongoing simulation such as data transfer, data analyses, and visualizations, etc. starts operations according to the requests during the simulation. The server makes the latest results available to web browsers, so that the collaborators can monitor the results at any place and time in the world. By applying the system to a specific simulation project of laser-matter interaction, we have confirmed that the system works well and plays an important role as a collaboration platform on which many collaborators work with one another

Programmed Nanomaterial Assemblies in Large Scales: Applications of Synthetic and Genetically- Engineered Peptides to Bridge Nano-Assemblies and Macro-Assemblies

Energy Technology Data Exchange (ETDEWEB)

Matsui, Hiroshi

2014-09-09

Work is reported in these areas: Large-scale & reconfigurable 3D structures of precise nanoparticle assemblies in self-assembled collagen peptide grids; Binary QD-Au NP 3D superlattices assembled with collagen-like peptides and energy transfer between QD and Au NP in 3D peptide frameworks; Catalytic peptides discovered by new hydrogel-based combinatorial phage display approach and their enzyme-mimicking 2D assembly; New autonomous motors of metal-organic frameworks (MOFs) powered by reorganization of self-assembled peptides at interfaces; Biomimetic assembly of proteins into microcapsules on oil-in-water droplets with structural reinforcement via biomolecular recognition-based cross-linking of surface peptides; and Biomimetic fabrication of strong freestanding genetically-engineered collagen peptide films reinforced by quantum dot joints. We gained the broad knowledge about biomimetic material assembly from nanoscale to microscale ranges by coassembling peptides and NPs via biomolecular recognition. We discovered: Genetically-engineered collagen-like peptides can be self-assembled with Au NPs to generate 3D superlattices in large volumes (> μm{sup 3}); The assembly of the 3D peptide-Au NP superstructures is dynamic and the interparticle distance changes with assembly time as the reconfiguration of structure is triggered by pH change; QDs/NPs can be assembled with the peptide frameworks to generate 3D superlattices and these QDs/NPs can be electronically coupled for the efficient energy transfer; The controlled assembly of catalytic peptides mimicking the catalytic pocket of enzymes can catalyze chemical reactions with high selectivity; and, For the bacteria-mimicking swimmer fabrication, peptide-MOF superlattices can power translational and propellant motions by the reconfiguration of peptide assembly at the MOF-liquid interface.

A Data Analysis Expert System For Large Established Distributed Databases

Science.gov (United States)

Gnacek, Anne-Marie; An, Y. Kim; Ryan, J. Patrick

1987-05-01

The purpose of this work is to analyze the applicability of artificial intelligence techniques for developing a user-friendly, parallel interface to large isolated, incompatible NASA databases for the purpose of assisting the management decision process. To carry out this work, a survey was conducted to establish the data access requirements of several key NASA user groups. In addition, current NASA database access methods were evaluated. The results of this work are presented in the form of a design for a natural language database interface system, called the Deductively Augmented NASA Management Decision Support System (DANMDS). This design is feasible principally because of recently announced commercial hardware and software product developments which allow cross-vendor compatibility. The goal of the DANMDS system is commensurate with the central dilemma confronting most large companies and institutions in America, the retrieval of information from large, established, incompatible database systems. The DANMDS system implementation would represent a significant first step toward this problem's resolution.

Molecular-dynamics simulations of polymeric surfaces for biomolecular applications

NARCIS (Netherlands)

Muntean, S.A.

2013-01-01

In-vitro diagnostics plays a very important role in the present healthcare system. It consists of a large variety of medical devices designed to diagnose a medical condition by measuring a target molecule in a sample, such as blood or urine. In vitro is the latin term for in glass and refers here to

Highly Scalable Trip Grouping for Large Scale Collective Transportation Systems

DEFF Research Database (Denmark)

Gidofalvi, Gyozo; Pedersen, Torben Bach; Risch, Tore

2008-01-01

Transportation-related problems, like road congestion, parking, and pollution, are increasing in most cities. In order to reduce traffic, recent work has proposed methods for vehicle sharing, for example for sharing cabs by grouping "closeby" cab requests and thus minimizing transportation cost...... and utilizing cab space. However, the methods published so far do not scale to large data volumes, which is necessary to facilitate large-scale collective transportation systems, e.g., ride-sharing systems for large cities. This paper presents highly scalable trip grouping algorithms, which generalize previous...

Study of grounding system of large tokamak device JT-60

International Nuclear Information System (INIS)

Arakawa, Kiyotsugu; Shimada, Ryuichi; Kishimoto, Hiroshi; Yabuno, Kohei; Ishigaki, Yukio.

1982-01-01

In the critical plasma testing facility JT-60 constructed by the Japan Atomic Energy Research Institute, high voltage, large current is required in an instant. Accordingly, for the protection of human bodies and the equipment, and for realizing the stable operation of the complex, precise control and measurement system, a large scale facility of grounding system is required. In case of the JT-60 experimental facility, the equipments with different functions in separate buildings are connected, therefore, it is an important point to avoid high potential difference between buildings. In the grounding system for the JT-60, a reticulate grounding electrode is laid for each building, and these electrodes are connected with a low impedance metallic duct called grounding trunk line. The power supply cables for various magnetic field coils, control lines and measurement lines are laid in the duct. It is a large problem to grasp quantitatively the effect of a grounding trunk line by analysis. The authors analyzed the phenomenon that large current flows into a grounding system by lightning strike or grounding. The fundamental construction of the grounding system for the JT-60, the condition for the analysis and the result of simulation are reported. (Kako, I.)

The convertible client/server technology in large container inspection system

International Nuclear Information System (INIS)

Chen Zhiqiang; Zhang Li; Gao Wenhuan; Kang Kejun

2001-01-01

The author presents a new convertible client/server technology in distributed networking environment of a large container inspection system. The characteristic and advantage of this technology is introduced. The authors illustrate the policy of the technology to develop the networking program, and provide one example about how to program the software in large container inspection system using the new technology

Two-level systems driven by large-amplitude fields

Science.gov (United States)

Nori, F.; Ashhab, S.; Johansson, J. R.; Zagoskin, A. M.

2009-03-01

We analyze the dynamics of a two-level system subject to driving by large-amplitude external fields, focusing on the resonance properties in the case of driving around the region of avoided level crossing. In particular, we consider three main questions that characterize resonance dynamics: (1) the resonance condition, (2) the frequency of the resulting oscillations on resonance, and (3) the width of the resonance. We identify the regions of validity of different approximations. In a large region of the parameter space, we use a geometric picture in order to obtain both a simple understanding of the dynamics and quantitative results. The geometric approach is obtained by dividing the evolution into discrete time steps, with each time step described by either a phase shift on the basis states or a coherent mixing process corresponding to a Landau-Zener crossing. We compare the results of the geometric picture with those of a rotating wave approximation. We also comment briefly on the prospects of employing strong driving as a useful tool to manipulate two-level systems. S. Ashhab, J.R. Johansson, A.M. Zagoskin, F. Nori, Two-level systems driven by large-amplitude fields, Phys. Rev. A 75, 063414 (2007). S. Ashhab et al, unpublished.

Local decoherence-resistant quantum states of large systems

Energy Technology Data Exchange (ETDEWEB)

Mishra, Utkarsh; Sen, Aditi; Sen, Ujjwal, E-mail: ujjwal@hri.res.in

2015-02-06

We identify an effectively decoherence-free class of quantum states, each of which consists of a “minuscule” and a “large” sector, against local noise. In particular, the content of entanglement and other quantum correlations in the minuscule to large partition is independent of the number of particles in their large sectors, when all the particles suffer passage through local amplitude and phase damping channels. The states of the large sectors are distinct in terms of markedly different amounts of violation of Bell inequality. In case the large sector is macroscopic, such states are akin to the Schrödinger cat. - Highlights: • We identify an effectively decoherence-free class of quantum states of large systems. • We work with local noise models. • Decay of entanglement as well as information-theoretic quantum correlations considered. • The states are of the form of the Schrödinger cats, with minuscule and large sectors. • The states of the large sector are distinguishable by their violation of Bell inequality.

Buffer provisioning for large-scale data-acquisition systems

CERN Document Server

AUTHOR|(SzGeCERN)756497; The ATLAS collaboration; Garcia Garcia, Pedro Javier; Froening, Holger; Vandelli, Wainer

2018-01-01

The data acquisition system of the ATLAS experiment, a major experiment of the Large Hadron Collider (LHC) at CERN, will go through a major upgrade in the next decade. The upgrade is driven by experimental physics requirements, calling for increased data rates on the order of 6~TB/s. By contrast, the data rate of the existing system is 160~GB/s. Among the changes in the upgraded system will be a very large buffer with a projected size on the order of 70 PB. The buffer role will be decoupling of data production from on-line data processing, storing data for periods of up to 24~hours until it can be analyzed by the event processing system. The larger buffer will allow a new data recording strategy, providing additional margins to handle variable data rates. At the same time it will provide sensible trade-offs between buffering space and on-line processing capabilities. This compromise between two resources will be possible since the data production cycle includes time periods where the experiment will not produ...

Biochemical Stability Analysis of Nano Scaled Contrast Agents Used in Biomolecular Imaging Detection of Tumor Cells

Science.gov (United States)

Kim, Jennifer; Kyung, Richard

Imaging contrast agents are materials used to improve the visibility of internal body structures in the imaging process. Many agents that are used for contrast enhancement are now studied empirically and computationally by researchers. Among various imaging techniques, magnetic resonance imaging (MRI) has become a major diagnostic tool in many clinical specialties due to its non-invasive characteristic and its safeness in regards to ionizing radiation exposure. Recently, researchers have prepared aqueous fullerene nanoparticles using electrochemical methods. In this paper, computational simulations of thermodynamic stabilities of nano scaled contrast agents that can be used in biomolecular imaging detection of tumor cells are presented using nanomaterials such as fluorescent functionalized fullerenes. In addition, the stability and safety of different types of contrast agents composed of metal oxide a, b, and c are tested in the imaging process. Through analysis of the computational simulations, the stabilities of the contrast agents, determined by optimized energies of the conformations, are presented. The resulting numerical data are compared. In addition, Density Functional Theory (DFT) is used in order to model the electron properties of the compound.

An advanced dispatching technology for large container inspection system

International Nuclear Information System (INIS)

Chen Zhiqiang; Zhang Li; Kang Kejun; Gao Wenhuan

2001-01-01

The author describes the transmitting and dispatching technology of large container inspection system. It introduces the structure of the double buffer graded pipe lining used in the system. Strategies of queue mechanism and waiting dispatch policy are illustrated

Steiner systems and large non-Hamiltonian hypergraphs

Directory of Open Access Journals (Sweden)

Zsolt Tuza

2006-10-01

Full Text Available From Steiner systems S(k − 2, 2k − 3, v, we construct k-uniform hyper- graphs of large size without Hamiltonian cycles. This improves previous estimates due to G. Y. Katona and H. Kierstead [J. Graph Theory 30 (1999, pp.  205–212].

A cyber-linked undergraduate research experience in computational biomolecular structure prediction and design.

Science.gov (United States)

Alford, Rebecca F; Leaver-Fay, Andrew; Gonzales, Lynda; Dolan, Erin L; Gray, Jeffrey J

2017-12-01

Computational biology is an interdisciplinary field, and many computational biology research projects involve distributed teams of scientists. To accomplish their work, these teams must overcome both disciplinary and geographic barriers. Introducing new training paradigms is one way to facilitate research progress in computational biology. Here, we describe a new undergraduate program in biomolecular structure prediction and design in which students conduct research at labs located at geographically-distributed institutions while remaining connected through an online community. This 10-week summer program begins with one week of training on computational biology methods development, transitions to eight weeks of research, and culminates in one week at the Rosetta annual conference. To date, two cohorts of students have participated, tackling research topics including vaccine design, enzyme design, protein-based materials, glycoprotein modeling, crowd-sourced science, RNA processing, hydrogen bond networks, and amyloid formation. Students in the program report outcomes comparable to students who participate in similar in-person programs. These outcomes include the development of a sense of community and increases in their scientific self-efficacy, scientific identity, and science values, all predictors of continuing in a science research career. Furthermore, the program attracted students from diverse backgrounds, which demonstrates the potential of this approach to broaden the participation of young scientists from backgrounds traditionally underrepresented in computational biology.

A cyber-linked undergraduate research experience in computational biomolecular structure prediction and design.

Directory of Open Access Journals (Sweden)

Rebecca F Alford

2017-12-01

Full Text Available Computational biology is an interdisciplinary field, and many computational biology research projects involve distributed teams of scientists. To accomplish their work, these teams must overcome both disciplinary and geographic barriers. Introducing new training paradigms is one way to facilitate research progress in computational biology. Here, we describe a new undergraduate program in biomolecular structure prediction and design in which students conduct research at labs located at geographically-distributed institutions while remaining connected through an online community. This 10-week summer program begins with one week of training on computational biology methods development, transitions to eight weeks of research, and culminates in one week at the Rosetta annual conference. To date, two cohorts of students have participated, tackling research topics including vaccine design, enzyme design, protein-based materials, glycoprotein modeling, crowd-sourced science, RNA processing, hydrogen bond networks, and amyloid formation. Students in the program report outcomes comparable to students who participate in similar in-person programs. These outcomes include the development of a sense of community and increases in their scientific self-efficacy, scientific identity, and science values, all predictors of continuing in a science research career. Furthermore, the program attracted students from diverse backgrounds, which demonstrates the potential of this approach to broaden the participation of young scientists from backgrounds traditionally underrepresented in computational biology.

Development of automated analytical systems for large throughput

International Nuclear Information System (INIS)

Ernst, P.C.; Hoffman, E.L.

1982-01-01

The need to be able to handle a large throughput of samples for neutron activation analysis has led to the development of automated counting and sample handling systems. These are coupled with available computer-assisted INAA techniques to perform a wide range of analytical services on a commercial basis. A fully automated delayed neutron counting system and a computer controlled pneumatic transfer for INAA use are described, as is a multi-detector gamma-spectroscopy system. (author)

Large Efficient Intelligent Heating Relay Station System

Science.gov (United States)

Wu, C. Z.; Wei, X. G.; Wu, M. Q.

2017-12-01

The design of large efficient intelligent heating relay station system aims at the improvement of the existing heating system in our country, such as low heating efficiency, waste of energy and serious pollution, and the control still depends on the artificial problem. In this design, we first improve the existing plate heat exchanger. Secondly, the ATM89C51 is used to control the whole system and realize the intelligent control. The detection part is using the PT100 temperature sensor, pressure sensor, turbine flowmeter, heating temperature, detection of user end liquid flow, hydraulic, and real-time feedback, feedback signal to the microcontroller through the heating for users to adjust, realize the whole system more efficient, intelligent and energy-saving.

Co-Immobilization of Proteins and DNA Origami Nanoplates to Produce High-Contrast Biomolecular Nanoarrays.

Science.gov (United States)

Hager, Roland; Burns, Jonathan R; Grydlik, Martyna J; Halilovic, Alma; Haselgrübler, Thomas; Schäffler, Friedrich; Howorka, Stefan

2016-06-01

The biofunctionalization of nanopatterned surfaces with DNA origami nanostructures is an important topic in nanobiotechnology. An unexplored challenge is, however, to co-immobilize proteins with DNA origami at pre-determined substrate sites in high contrast relative to the nontarget areas. The immobilization should, in addition, preferably be achieved on a transparent substrate to allow ultrasensitive optical detection. If successful, specific co-binding would be a step towards stoichiometrically defined arrays with few to individual protein molecules per site. Here, we successfully immobilize with high specificity positively charged avidin proteins and negatively charged DNA origami nanoplates on 100 nm-wide carbon nanoislands while suppressing undesired adsorption to surrounding nontarget areas. The arrays on glass slides achieve unprecedented selectivity factors of up to 4000 and allow ultrasensitive fluorescence read-out. The co-immobilization onto the nanoislands leads to layered biomolecular architectures, which are functional because bound DNA origami influences the number of capturing sites on the nanopatches for other proteins. The novel hybrid DNA origami-protein nanoarrays allow the fabrication of versatile research platforms for applications in biosensing, biophysics, and cell biology, and, in addition, represent an important step towards single-molecule protein arrays. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discerning molecular interactions: A comprehensive review on biomolecular interaction databases and network analysis tools.

Science.gov (United States)

Miryala, Sravan Kumar; Anbarasu, Anand; Ramaiah, Sudha

2018-02-05

Computational analysis of biomolecular interaction networks is now gaining a lot of importance to understand the functions of novel genes/proteins. Gene interaction (GI) network analysis and protein-protein interaction (PPI) network analysis play a major role in predicting the functionality of interacting genes or proteins and gives an insight into the functional relationships and evolutionary conservation of interactions among the genes. An interaction network is a graphical representation of gene/protein interactome, where each gene/protein is a node, and interaction between gene/protein is an edge. In this review, we discuss the popular open source databases that serve as data repositories to search and collect protein/gene interaction data, and also tools available for the generation of interaction network, visualization and network analysis. Also, various network analysis approaches like topological approach and clustering approach to study the network properties and functional enrichment server which illustrates the functions and pathway of the genes and proteins has been discussed. Hence the distinctive attribute mentioned in this review is not only to provide an overview of tools and web servers for gene and protein-protein interaction (PPI) network analysis but also to extract useful and meaningful information from the interaction networks. Copyright © 2017 Elsevier B.V. All rights reserved.

Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets.

Science.gov (United States)

Prendergast, Mary E; Buckley, Michael; Crowther, Alison; Frantz, Laurent; Eager, Heidi; Lebrasseur, Ophélie; Hutterer, Rainer; Hulme-Beaman, Ardern; Van Neer, Wim; Douka, Katerina; Veall, Margaret-Ashley; Quintana Morales, Eréndira M; Schuenemann, Verena J; Reiter, Ella; Allen, Richard; Dimopoulos, Evangelos A; Helm, Richard M; Shipton, Ceri; Mwebi, Ogeto; Denys, Christiane; Horton, Mark; Wynne-Jones, Stephanie; Fleisher, Jeffrey; Radimilahy, Chantal; Wright, Henry; Searle, Jeremy B; Krause, Johannes; Larson, Greger; Boivin, Nicole L

2017-01-01

Human-mediated biological exchange has had global social and ecological impacts. In sub-Saharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation.

Beyond Multiplexing Gain in Large MIMO Systems

DEFF Research Database (Denmark)

Cakmak, Burak; Müller, Ralf R.; Fleury, Bernard Henri

growth (multiplexing gain). Even when the channel entries are i.i.d. the deviation from the linear growth is significant. We also find an additive property of the deviation for a concatenated MIMO system. Finally, we quantify the deviation of the large SNR capacity from the exact capacity and find...

Report of the Workshop on Petascale Systems Integration for LargeScale Facilities

Energy Technology Data Exchange (ETDEWEB)

Kramer, William T.C.; Walter, Howard; New, Gary; Engle, Tom; Pennington, Rob; Comes, Brad; Bland, Buddy; Tomlison, Bob; Kasdorf, Jim; Skinner, David; Regimbal, Kevin

2007-10-01

There are significant issues regarding Large Scale System integration that are not being addressed in other forums such as current research portfolios or vendor user groups. Unfortunately, the issues in the area of large-scale system integration often fall into a netherworld; not research, not facilities, not procurement, not operations, not user services. Taken together, these issues along with the impact of sub-optimal integration technology means the time required to deploy, integrate and stabilize large scale system may consume up to 20 percent of the useful life of such systems. Improving the state of the art for large scale systems integration has potential to increase the scientific productivity of these systems. Sites have significant expertise, but there are no easy ways to leverage this expertise among them . Many issues inhibit the sharing of information, including available time and effort, as well as issues with sharing proprietary information. Vendors also benefit in the long run from the solutions to issues detected during site testing and integration. There is a great deal of enthusiasm for making large scale system integration a full-fledged partner along with the other major thrusts supported by funding agencies in the definition, design, and use of a petascale systems. Integration technology and issues should have a full 'seat at the table' as petascale and exascale initiatives and programs are planned. The workshop attendees identified a wide range of issues and suggested paths forward. Pursuing these with funding opportunities and innovation offers the opportunity to dramatically improve the state of large scale system integration.

Software Reliability Issues Concerning Large and Safety Critical Software Systems

Science.gov (United States)

Kamel, Khaled; Brown, Barbara

1996-01-01

This research was undertaken to provide NASA with a survey of state-of-the-art techniques using in industrial and academia to provide safe, reliable, and maintainable software to drive large systems. Such systems must match the complexity and strict safety requirements of NASA's shuttle system. In particular, the Launch Processing System (LPS) is being considered for replacement. The LPS is responsible for monitoring and commanding the shuttle during test, repair, and launch phases. NASA built this system in the 1970's using mostly hardware techniques to provide for increased reliability, but it did so often using custom-built equipment, which has not been able to keep up with current technologies. This report surveys the major techniques used in industry and academia to ensure reliability in large and critical computer systems.

Steady-state analysis of large scale systems : the successive lumping method

NARCIS (Netherlands)

Smit, L.C.

2016-01-01

The general area of research of this dissertation concerns large systems with random aspects to their behavior that can be modeled and studied in terms of the stationary distribution of Markov chains. As the state spaces of such systems become large, their behavior gets hard to analyze, either via

Krylov subspace methods for the solution of large systems of ODE's

DEFF Research Database (Denmark)

Thomsen, Per Grove; Bjurstrøm, Nils Henrik

1998-01-01

In Air Pollution Modelling large systems of ODE's arise. Solving such systems may be done efficientliy by Semi Implicit Runge-Kutta methods. The internal stages may be solved using Krylov subspace methods. The efficiency of this approach is investigated and verified.......In Air Pollution Modelling large systems of ODE's arise. Solving such systems may be done efficientliy by Semi Implicit Runge-Kutta methods. The internal stages may be solved using Krylov subspace methods. The efficiency of this approach is investigated and verified....

Large Scale Landslide Database System Established for the Reservoirs in Southern Taiwan

Science.gov (United States)

Tsai, Tsai-Tsung; Tsai, Kuang-Jung; Shieh, Chjeng-Lun

2017-04-01

Typhoon Morakot seriously attack southern Taiwan awaken the public awareness of large scale landslide disasters. Large scale landslide disasters produce large quantity of sediment due to negative effects on the operating functions of reservoirs. In order to reduce the risk of these disasters within the study area, the establishment of a database for hazard mitigation / disaster prevention is necessary. Real time data and numerous archives of engineering data, environment information, photo, and video, will not only help people make appropriate decisions, but also bring the biggest concern for people to process and value added. The study tried to define some basic data formats / standards from collected various types of data about these reservoirs and then provide a management platform based on these formats / standards. Meanwhile, in order to satisfy the practicality and convenience, the large scale landslide disasters database system is built both provide and receive information abilities, which user can use this large scale landslide disasters database system on different type of devices. IT technology progressed extreme quick, the most modern system might be out of date anytime. In order to provide long term service, the system reserved the possibility of user define data format /standard and user define system structure. The system established by this study was based on HTML5 standard language, and use the responsive web design technology. This will make user can easily handle and develop this large scale landslide disasters database system.

Energy cascading in large district heating systems

International Nuclear Information System (INIS)

Mayer, F.W.

1978-01-01

District heat transfer is the most economical utilization of the waste heat of power plants. Optimum utilization and heat transfer over large distances are possible because of a new energy distribution system, the ''energy cascading system,'' in which heat is transferred to several consumer regions at different temperature ranges. It is made more profitable by the use of heat pumps. The optimum flow-line temperature is 368 0 K, and the optimum return-line temperature is 288 0 K, resulting in an approximately 50% reduction of electric power loss at the power plant

A review of large-scale solar heating systems in Europe

International Nuclear Information System (INIS)

Fisch, M.N.; Guigas, M.; Dalenback, J.O.

1998-01-01

Large-scale solar applications benefit from the effect of scale. Compared to small solar domestic hot water (DHW) systems for single-family houses, the solar heat cost can be cut at least in third. The most interesting projects for replacing fossil fuels and the reduction of CO 2 -emissions are solar systems with seasonal storage in combination with gas or biomass boilers. In the framework of the EU-APAS project Large-scale Solar Heating Systems, thirteen existing plants in six European countries have been evaluated. lie yearly solar gains of the systems are between 300 and 550 kWh per m 2 collector area. The investment cost of solar plants with short-term storage varies from 300 up to 600 ECU per m 2 . Systems with seasonal storage show investment costs twice as high. Results of studies concerning the market potential for solar heating plants, taking new collector concepts and industrial production into account, are presented. Site specific studies and predesign of large-scale solar heating plants in six European countries for housing developments show a 50% cost reduction compared to existing projects. The cost-benefit-ratio for the planned systems with long-term storage is between 0.7 and 1.5 ECU per kWh per year. (author)

Data management strategies for multinational large-scale systems biology projects.

Science.gov (United States)

Wruck, Wasco; Peuker, Martin; Regenbrecht, Christian R A

2014-01-01

Good accessibility of publicly funded research data is essential to secure an open scientific system and eventually becomes mandatory [Wellcome Trust will Penalise Scientists Who Don't Embrace Open Access. The Guardian 2012]. By the use of high-throughput methods in many research areas from physics to systems biology, large data collections are increasingly important as raw material for research. Here, we present strategies worked out by international and national institutions targeting open access to publicly funded research data via incentives or obligations to share data. Funding organizations such as the British Wellcome Trust therefore have developed data sharing policies and request commitment to data management and sharing in grant applications. Increased citation rates are a profound argument for sharing publication data. Pre-publication sharing might be rewarded by a data citation credit system via digital object identifiers (DOIs) which have initially been in use for data objects. Besides policies and incentives, good practice in data management is indispensable. However, appropriate systems for data management of large-scale projects for example in systems biology are hard to find. Here, we give an overview of a selection of open-source data management systems proved to be employed successfully in large-scale projects.

Large-scale computing techniques for complex system simulations

CERN Document Server

Dubitzky, Werner; Schott, Bernard

2012-01-01

Complex systems modeling and simulation approaches are being adopted in a growing number of sectors, including finance, economics, biology, astronomy, and many more. Technologies ranging from distributed computing to specialized hardware are explored and developed to address the computational requirements arising in complex systems simulations. The aim of this book is to present a representative overview of contemporary large-scale computing technologies in the context of complex systems simulations applications. The intention is to identify new research directions in this field and

Distributed and hierarchical control techniques for large-scale power plant systems

International Nuclear Information System (INIS)

Raju, G.V.S.; Kisner, R.A.

1985-08-01

In large-scale systems, integrated and coordinated control functions are required to maximize plant availability, to allow maneuverability through various power levels, and to meet externally imposed regulatory limitations. Nuclear power plants are large-scale systems. Prime subsystems are those that contribute directly to the behavior of the plant's ultimate output. The prime subsystems in a nuclear power plant include reactor, primary and intermediate heat transport, steam generator, turbine generator, and feedwater system. This paper describes and discusses the continuous-variable control system developed to supervise prime plant subsystems for optimal control and coordination

Glass badge dosimetry system for large scale personal monitoring

International Nuclear Information System (INIS)

Norimichi Juto

2002-01-01

Glass Badge using silver activated phosphate glass dosemeter was specially developed for large scale personal monitoring. And dosimetry systems such as an automatic leader and a dose equipment calculation algorithm were developed at once to achieve reasonable personal monitoring. In large scale personal monitoring, both of precision for dosimetry and confidence for lot of personal data handling become very important. The silver activated phosphate glass dosemeter has basically excellent characteristics for dosimetry such as homogeneous and stable sensitivity, negligible fading and so on. Glass Badge was designed to measure 10 keV - 10 MeV range of photon. 300 keV - 3 MeV range of beta, and 0.025 eV - 15 MeV range of neutron by included SSNTD. And developed Glass Badge dosimetry system has not only these basic characteristics but also lot of features to keep good precision for dosimetry and data handling. In this presentation, features of Glass Badge dosimetry systems and examples for practical personal monitoring systems will be presented. (Author)

Sequential decoders for large MIMO systems

KAUST Repository

Ali, Konpal S.

2014-05-01

Due to their ability to provide high data rates, multiple-input multiple-output (MIMO) systems have become increasingly popular. Decoding of these systems with acceptable error performance is computationally very demanding. In this paper, we employ the Sequential Decoder using the Fano Algorithm for large MIMO systems. A parameter called the bias is varied to attain different performance-complexity trade-offs. Low values of the bias result in excellent performance but at the expense of high complexity and vice versa for higher bias values. Numerical results are done that show moderate bias values result in a decent performance-complexity trade-off. We also attempt to bound the error by bounding the bias, using the minimum distance of a lattice. The variations in complexity with SNR have an interesting trend that shows room for considerable improvement. Our work is compared against linear decoders (LDs) aided with Element-based Lattice Reduction (ELR) and Complex Lenstra-Lenstra-Lovasz (CLLL) reduction. © 2014 IFIP.

Verifying large modular systems using iterative abstraction refinement

International Nuclear Information System (INIS)

Lahtinen, Jussi; Kuismin, Tuomas; Heljanko, Keijo

2015-01-01

Digital instrumentation and control (I&C) systems are increasingly used in the nuclear engineering domain. The exhaustive verification of these systems is challenging, and the usual verification methods such as testing and simulation are typically insufficient. Model checking is a formal method that is able to exhaustively analyse the behaviour of a model against a formally written specification. If the model checking tool detects a violation of the specification, it will give out a counter-example that demonstrates how the specification is violated in the system. Unfortunately, sometimes real life system designs are too big to be directly analysed by traditional model checking techniques. We have developed an iterative technique for model checking large modular systems. The technique uses abstraction based over-approximations of the model behaviour, combined with iterative refinement. The main contribution of the work is the concrete abstraction refinement technique based on the modular structure of the model, the dependency graph of the model, and a refinement sampling heuristic similar to delta debugging. The technique is geared towards proving properties, and outperforms BDD-based model checking, the k-induction technique, and the property directed reachability algorithm (PDR) in our experiments. - Highlights: • We have developed an iterative technique for model checking large modular systems. • The technique uses BDD-based model checking, k-induction, and PDR in parallel. • We have tested our algorithm by verifying two models with it. • The technique outperforms classical model checking methods in our experiments

Reduction of Large Dynamical Systems by Minimization of Evolution Rate

Science.gov (United States)

Girimaji, Sharath S.

1999-01-01

Reduction of a large system of equations to a lower-dimensional system of similar dynamics is investigated. For dynamical systems with disparate timescales, a criterion for determining redundant dimensions and a general reduction method based on the minimization of evolution rate are proposed.

Defining Execution Viewpoints for a Large and Complex Software-Intensive System

OpenAIRE

Callo Arias, Trosky B.; America, Pierre; Avgeriou, Paris

2009-01-01

An execution view is an important asset for developing large and complex systems. An execution view helps practitioners to describe, analyze, and communicate what a software system does at runtime and how it does it. In this paper, we present an approach to define execution viewpoints for an existing large and complex software-intensive system. This definition approach enables the customization and extension of a set of predefined viewpoints to address the requirements of a specific developme...

Accuracy of the photogrametric measuring system for large size elements

Directory of Open Access Journals (Sweden)

M. Grzelka

2011-04-01

Full Text Available The aim of this paper is to present methods of estimating and guidelines for verifying the accuracy of optical photogrammetric measuringsystems, using for measurement of large size elements. Measuring systems applied to measure workpieces of a large size which oftenreach more than 10000mm require use of appropriate standards. Those standards provided by the manufacturer of photogrammetricsystems are certified and are inspected annually. To make sure that these systems work properly there was developed a special standardVDI / VDE 2634, "Optical 3D measuring systems. Imaging systems with point - by - point probing. " According to recommendationsdescribed in this standard research on accuracy of photogrametric measuring system was conducted using K class gauge blocks dedicatedto calibrate and test accuracy of classic CMMs. The paper presents results of research of estimation the actual error of indication for sizemeasurement MPEE for photogrammetric coordinate measuring system TRITOP.

Large scale gas chromatographic demonstration system for hydrogen isotope separation

International Nuclear Information System (INIS)

Cheh, C.H.

1988-01-01

A large scale demonstration system was designed for a throughput of 3 mol/day equimolar mixture of H,D, and T. The demonstration system was assembled and an experimental program carried out. This project was funded by Kernforschungszentrum Karlsruhe, Canadian Fusion Fuel Technology Projects and Ontario Hydro Research Division. Several major design innovations were successfully implemented in the demonstration system and are discussed in detail. Many experiments were carried out in the demonstration system to study the performance of the system to separate hydrogen isotopes at high throughput. Various temperature programming schemes were tested, heart-cutting operation was evaluated, and very large (up to 138 NL/injection) samples were separated in the system. The results of the experiments showed that the specially designed column performed well as a chromatographic column and good separation could be achieved even when a 138 NL sample was injected

Evaluation of biomolecular distributions in rat brain tissues by means of ToF-SIMS using a continuous beam of Ar clusters.

Science.gov (United States)

Nakano, Shusuke; Yokoyama, Yuta; Aoyagi, Satoka; Himi, Naoyuki; Fletcher, John S; Lockyer, Nicholas P; Henderson, Alex; Vickerman, John C

2016-06-08

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides detailed chemical structure information and high spatial resolution images. Therefore, ToF-SIMS is useful for studying biological phenomena such as ischemia. In this study, in order to evaluate cerebral microinfarction, the distribution of biomolecules generated by ischemia was measured with ToF-SIMS. ToF-SIMS data sets were analyzed by means of multivariate analysis for interpreting complex samples containing unknown information and to obtain biomolecular mapping indicated by fragment ions from the target biomolecules. Using conventional ToF-SIMS (primary ion source: Bi cluster ion), it is difficult to detect secondary ions beyond approximately 1000 u. Moreover, the intensity of secondary ions related to biomolecules is not always high enough for imaging because of low concentration even if the masses are lower than 1000 u. However, for the observation of biomolecular distributions in tissues, it is important to detect low amounts of biological molecules from a particular area of tissue. Rat brain tissue samples were measured with ToF-SIMS (J105, Ionoptika, Ltd., Chandlers Ford, UK), using a continuous beam of Ar clusters as a primary ion source. ToF-SIMS with Ar clusters efficiently detects secondary ions related to biomolecules and larger molecules. Molecules detected by ToF-SIMS were examined by analyzing ToF-SIMS data using multivariate analysis. Microspheres (45 μm diameter) were injected into the rat unilateral internal carotid artery (MS rat) to cause cerebral microinfarction. The rat brain was sliced and then measured with ToF-SIMS. The brain samples of a normal rat and the MS rat were examined to find specific secondary ions related to important biomolecules, and then the difference between them was investigated. Finally, specific secondary ions were found around vessels incorporating microspheres in the MS rat. The results suggest that important biomolecules related to cerebral

Improved control system power unit for large parachutes

Science.gov (United States)

Chandler, J. A.; Grubbs, T. M.

1968-01-01

Improved control system power unit drives the control surfaces of very large controllable parachutes. The design features subassemblies for determining control surface position and cable loading, and protection of the load sensor against the possibility of damage during manipulation.

Testing, development and demonstration of large scale solar district heating systems

DEFF Research Database (Denmark)

Furbo, Simon; Fan, Jianhua; Perers, Bengt

2015-01-01

In 2013-2014 the project “Testing, development and demonstration of large scale solar district heating systems” was carried out within the Sino-Danish Renewable Energy Development Programme, the so called RED programme jointly developed by the Chinese and Danish governments. In the project Danish...... know how on solar heating plants and solar heating test technology have been transferred from Denmark to China, large solar heating systems have been promoted in China, test capabilities on solar collectors and large scale solar heating systems have been improved in China and Danish-Chinese cooperation...

Distributed system for large-scale remote research

International Nuclear Information System (INIS)

Ueshima, Yutaka

2002-01-01

In advanced photon research, large-scale simulations and high-resolution observations are powerfull tools. In numerical and real experiments, the real-time visualization and steering system is considered as a hopeful method of data analysis. This approach is valid in the typical analysis at one time or low cost experiment and simulation. In research of an unknown problem, it is necessary that the output data be analyzed many times because conclusive analysis is difficult at one time. Consequently, output data should be filed to refer and analyze at any time. To support research, we need the automatic functions, transporting data files from data generator to data storage, analyzing data, tracking history of data handling, and so on. The supporting system will be a functionally distributed system. (author)

Disruptions in large value payment systems: an experimental approach

NARCIS (Netherlands)

Abbink, K.; Bosman, R.; Heijmans, R.; van Winden, F.

2010-01-01

This experimental study investigates the behaviour of banks in a large value payment system. More specifically,we look at 1) the reactions of banks to disruptions in the payment system, 2) the way in which the history of disruptions affects the behaviour of banks (path dependency) and 3) the effect

Disruptions in large value payment systems: An experimental approach

NARCIS (Netherlands)

Abbink, K.; Bosman, R.; Heijmans, R.; van Winden, F.; Hellqvist, M.; Laine, T.

2012-01-01

This experimental study investigates the behaviour of banks in a large value payment system. More specifically, we look at 1) the reactions of banks to disruptions in the payment system, 2) the way in which the history of disruptions affects the behaviour of banks (path dependency) and 3) the effect

Large amplitude forced vibration analysis of cross-beam system ...

African Journals Online (AJOL)

Large amplitude forced vibration behaviour of cross-beam system under harmonic excitation is studied, incorporating the effect of geometric non-linearity. The forced vibration analysis is carried out in an indirect way, in which the dynamic system is assumed to satisfy the force equilibrium condition at peak load value, thus ...

Jump phenomena. [large amplitude responses of nonlinear systems

Science.gov (United States)

Reiss, E. L.

1980-01-01

The paper considers jump phenomena composed of large amplitude responses of nonlinear systems caused by small amplitude disturbances. Physical problems where large jumps in the solution amplitude are important features of the response are described, including snap buckling of elastic shells, chemical reactions leading to combustion and explosion, and long-term climatic changes of the earth's atmosphere. A new method of rational functions was then developed which consists of representing the solutions of the jump problems as rational functions of the small disturbance parameter; this method can solve jump problems explicitly.

Highly uniform parallel microfabrication using a large numerical aperture system

Energy Technology Data Exchange (ETDEWEB)

Zhang, Zi-Yu; Su, Ya-Hui, E-mail: ustcsyh@ahu.edu.cn, E-mail: dongwu@ustc.edu.cn [School of Electrical Engineering and Automation, Anhui University, Hefei 230601 (China); Zhang, Chen-Chu; Hu, Yan-Lei; Wang, Chao-Wei; Li, Jia-Wen; Chu, Jia-Ru; Wu, Dong, E-mail: ustcsyh@ahu.edu.cn, E-mail: dongwu@ustc.edu.cn [CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei 230026 (China)

2016-07-11

In this letter, we report an improved algorithm to produce accurate phase patterns for generating highly uniform diffraction-limited multifocal arrays in a large numerical aperture objective system. It is shown that based on the original diffraction integral, the uniformity of the diffraction-limited focal arrays can be improved from ∼75% to >97%, owing to the critical consideration of the aperture function and apodization effect associated with a large numerical aperture objective. The experimental results, e.g., 3 × 3 arrays of square and triangle, seven microlens arrays with high uniformity, further verify the advantage of the improved algorithm. This algorithm enables the laser parallel processing technology to realize uniform microstructures and functional devices in the microfabrication system with a large numerical aperture objective.

SPATKIN: a simulator for rule-based modeling of biomolecular site dynamics on surfaces.

Science.gov (United States)

Kochanczyk, Marek; Hlavacek, William S; Lipniacki, Tomasz

2017-11-15

Rule-based modeling is a powerful approach for studying biomolecular site dynamics. Here, we present SPATKIN, a general-purpose simulator for rule-based modeling in two spatial dimensions. The simulation algorithm is a lattice-based method that tracks Brownian motion of individual molecules and the stochastic firing of rule-defined reaction events. Because rules are used as event generators, the algorithm is network-free, meaning that it does not require to generate the complete reaction network implied by rules prior to simulation. In a simulation, each molecule (or complex of molecules) is taken to occupy a single lattice site that cannot be shared with another molecule (or complex). SPATKIN is capable of simulating a wide array of membrane-associated processes, including adsorption, desorption and crowding. Models are specified using an extension of the BioNetGen language, which allows to account for spatial features of the simulated process. The C ++ source code for SPATKIN is distributed freely under the terms of the GNU GPLv3 license. The source code can be compiled for execution on popular platforms (Windows, Mac and Linux). An installer for 64-bit Windows and a macOS app are available. The source code and precompiled binaries are available at the SPATKIN Web site (http://pmbm.ippt.pan.pl/software/spatkin). spatkin.simulator@gmail.com. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Large-scale theoretical calculations in molecular science - design of a large computer system for molecular science and necessary conditions for future computers

Energy Technology Data Exchange (ETDEWEB)

Kashiwagi, H [Institute for Molecular Science, Okazaki, Aichi (Japan)

1982-06-01

A large computer system was designed and established for molecular science under the leadership of molecular scientists. Features of the computer system are an automated operation system and an open self-service system. Large-scale theoretical calculations have been performed to solve many problems in molecular science, using the computer system. Necessary conditions for future computers are discussed on the basis of this experience.

Large-scale theoretical calculations in molecular science - design of a large computer system for molecular science and necessary conditions for future computers

International Nuclear Information System (INIS)

Kashiwagi, H.

1982-01-01

A large computer system was designed and established for molecular science under the leadership of molecular scientists. Features of the computer system are an automated operation system and an open self-service system. Large-scale theoretical calculations have been performed to solve many problems in molecular science, using the computer system. Necessary conditions for future computers are discussed on the basis of this experience. (orig.)

Large superconducting magnet systems for plasma and fusion applications

International Nuclear Information System (INIS)

Heinz, W.

1976-05-01

Work on superconducting magnet systems and state of the art of superconducting magnet technology are described. Conceptual design consideration and problems of large magnet systems (stability, magnetic forces, cooling modes, safety) are discussed. Recent results of experimental work at Karlsruhe are reported. An outline of American and European programs is given. (orig.) [de

Power quality load management for large spacecraft electrical power systems

Science.gov (United States)

Lollar, Louis F.

1988-01-01

In December, 1986, a Center Director's Discretionary Fund (CDDF) proposal was granted to study power system control techniques in large space electrical power systems. Presented are the accomplishments in the area of power system control by power quality load management. In addition, information concerning the distortion problems in a 20 kHz ac power system is presented.

From a Proven Correct Microkernel to Trustworthy Large Systems

Science.gov (United States)

Andronick, June

The seL4 microkernel was the world's first general-purpose operating system kernel with a formal, machine-checked proof of correctness. The next big step in the challenge of building truly trustworthy systems is to provide a framework for developing secure systems on top of seL4. This paper first gives an overview of seL4's correctness proof, together with its main implications and assumptions, and then describes our approach to provide formal security guarantees for large, complex systems.

Studying chemical reactions in biological systems with MBN Explorer

DEFF Research Database (Denmark)

Sushko, Gennady B.; Solov'yov, Ilia A.; Verkhovtsev, Alexey V.

2016-01-01

The concept of molecular mechanics force field has been widely accepted nowadays for studying various processes in biomolecular systems. In this paper, we suggest a modification for the standard CHARMM force field that permits simulations of systems with dynamically changing molecular topologies....... The implementation of the modified force field was carried out in the popular program MBN Explorer, and, to support the development, we provide several illustrative case studies where dynamical topology is necessary. In particular, it is shown that the modified molecular mechanics force field can be applied...

A novel reliability evaluation method for large engineering systems

Directory of Open Access Journals (Sweden)

Reda Farag

2016-06-01

Full Text Available A novel reliability evaluation method for large nonlinear engineering systems excited by dynamic loading applied in time domain is presented. For this class of problems, the performance functions are expected to be function of time and implicit in nature. Available first- or second-order reliability method (FORM/SORM will be challenging to estimate reliability of such systems. Because of its inefficiency, the classical Monte Carlo simulation (MCS method also cannot be used for large nonlinear dynamic systems. In the proposed approach, only tens instead of hundreds or thousands of deterministic evaluations at intelligently selected points are used to extract the reliability information. A hybrid approach, consisting of the stochastic finite element method (SFEM developed by the author and his research team using FORM, response surface method (RSM, an interpolation scheme, and advanced factorial schemes, is proposed. The method is clarified with the help of several numerical examples.

Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets.

Directory of Open Access Journals (Sweden)

Mary E Prendergast

Full Text Available Human-mediated biological exchange has had global social and ecological impacts. In sub-Saharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus and black rat (Rattus rattus. Our approach included ancient DNA (aDNA analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS collagen fingerprinting, and direct AMS (accelerator mass spectrometry radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation.

Dynamic Reactive Power Compensation of Large Scale Wind Integrated Power System

DEFF Research Database (Denmark)

Rather, Zakir Hussain; Chen, Zhe; Thøgersen, Paul

2015-01-01

wind turbines especially wind farms with additional grid support functionalities like dynamic support (e,g dynamic reactive power support etc.) and ii) refurbishment of existing conventional central power plants to synchronous condensers could be one of the efficient, reliable and cost effective option......Due to progressive displacement of conventional power plants by wind turbines, dynamic security of large scale wind integrated power systems gets significantly compromised. In this paper we first highlight the importance of dynamic reactive power support/voltage security in large scale wind...... integrated power systems with least presence of conventional power plants. Then we propose a mixed integer dynamic optimization based method for optimal dynamic reactive power allocation in large scale wind integrated power systems. One of the important aspects of the proposed methodology is that unlike...

Large picture archiving and communication systems of the world--Part 2.

Science.gov (United States)

Bauman, R A; Gell, G; Dwyer, S J

1996-11-01

A survey of 82 institutions worldwide was done in 1995 to identify large picture archiving and communication systems (PACS) in clinical operation. A continuing strong trend toward the creation and operation of large PACS was identified. In the 15 months since the first such survey the number of clinical large PACS went from 13 to 23, almost a doubling in that short interval. New systems were added in Asia, Europe, and North America. A strong move to primary interpretation from soft copy was identified, and filmless radiology has become a reality. Workstations for interpretation reside mainly within radiology, but one-third of reporting PACS have more than 20 workstations outside of radiology. Fiber distributed data interface networks were the most numerous, but a variety of networks was reported to be in use. Replies on various display times showed surprisingly good, albeit diverse, speeds. The planned archive length of many systems was 60 months, with usually more than 1 year of data on-line. The main large archive and off-line storage media for these systems were optical disks and magneto-optical disks. Compression was not used before interpretation in most cases, but many systems used 2.5:1 compression for on-line, interpreted cases and 10:1 compression for longer-term archiving. A move to digital imaging and communication in medicine interface usage was identified.

Electro-mechanical probe positioning system for large volume plasma device

Science.gov (United States)

Sanyasi, A. K.; Sugandhi, R.; Srivastava, P. K.; Srivastav, Prabhakar; Awasthi, L. M.

2018-05-01

An automated electro-mechanical system for the positioning of plasma diagnostics has been designed and implemented in a Large Volume Plasma Device (LVPD). The system consists of 12 electro-mechanical assemblies, which are orchestrated using the Modbus communication protocol on 4-wire RS485 communications to meet the experimental requirements. Each assembly has a lead screw-based mechanical structure, Wilson feed-through-based vacuum interface, bipolar stepper motor, micro-controller-based stepper drive, and optical encoder for online positioning correction of probes. The novelty of the system lies in the orchestration of multiple drives on a single interface, fabrication and installation of the system for a large experimental device like the LVPD, in-house developed software, and adopted architectural practices. The paper discusses the design, description of hardware and software interfaces, and performance results in LVPD.

Bake-Out Mobile Controls for Large Vacuum Systems

CERN Document Server

Blanchard, S; Gomes, P; Pereira, H; Kopylov, L; Merker, S; Mikheev, M

2014-01-01

Large vacuum systems at CERN (Large Hadron Collider - LHC, Low Energy Ion Rings - LEIR...) require bake-out to achieve ultra-high vacuum specifications. The bake-out cycle is used to decrease the outgassing rate of the vacuum vessel and to activate the Non-Evaporable Getter (NEG) thin film. Bake-out control is a Proportional-Integral-Derivative (PID) regulation with complex recipes, interlocks and troubleshooting management and remote control. It is based on mobile Programmable Logic Controller (PLC) cabinets, fieldbus network and Supervisory Control and Data Acquisition (SCADA) application. The CERN vacuum installations include more than 7 km of baked vessels; using mobile cabinets reduces considerably the cost of the control system. The cabinets are installed close to the vacuum vessels during the time of the bake-out cycle. Mobile cabinets can be used in any of the CERN vacuum facilities. Remote control is provided through a fieldbus network and a SCADA application

System Dynamics Simulation of Large-Scale Generation System for Designing Wind Power Policy in China

Directory of Open Access Journals (Sweden)

Linna Hou

2015-01-01

Full Text Available This paper focuses on the impacts of renewable energy policy on a large-scale power generation system, including thermal power, hydropower, and wind power generation. As one of the most important clean energy, wind energy has been rapidly developed in the world. But in recent years there is a serious waste of wind power equipment and investment in China leading to many problems in the industry from wind power planning to its integration. One way overcoming the difficulty is to analyze the influence of wind power policy on a generation system. This paper builds a system dynamics (SD model of energy generation to simulate the results of wind energy generation policies based on a complex system. And scenario analysis method is used to compare the effectiveness and efficiency of these policies. The case study shows that the combinations of lower portfolio goal and higher benchmark price and those of higher portfolio goal and lower benchmark price have large differences in both effectiveness and efficiency. On the other hand, the combinations of uniformly lower or higher portfolio goal and benchmark price have similar efficiency, but different effectiveness. Finally, an optimal policy combination can be chosen on the basis of policy analysis in the large-scale power system.

High-Performance Monitoring Architecture for Large-Scale Distributed Systems Using Event Filtering

Science.gov (United States)

Maly, K.

1998-01-01

Monitoring is an essential process to observe and improve the reliability and the performance of large-scale distributed (LSD) systems. In an LSD environment, a large number of events is generated by the system components during its execution or interaction with external objects (e.g. users or processes). Monitoring such events is necessary for observing the run-time behavior of LSD systems and providing status information required for debugging, tuning and managing such applications. However, correlated events are generated concurrently and could be distributed in various locations in the applications environment which complicates the management decisions process and thereby makes monitoring LSD systems an intricate task. We propose a scalable high-performance monitoring architecture for LSD systems to detect and classify interesting local and global events and disseminate the monitoring information to the corresponding end- points management applications such as debugging and reactive control tools to improve the application performance and reliability. A large volume of events may be generated due to the extensive demands of the monitoring applications and the high interaction of LSD systems. The monitoring architecture employs a high-performance event filtering mechanism to efficiently process the large volume of event traffic generated by LSD systems and minimize the intrusiveness of the monitoring process by reducing the event traffic flow in the system and distributing the monitoring computation. Our architecture also supports dynamic and flexible reconfiguration of the monitoring mechanism via its Instrumentation and subscription components. As a case study, we show how our monitoring architecture can be utilized to improve the reliability and the performance of the Interactive Remote Instruction (IRI) system which is a large-scale distributed system for collaborative distance learning. The filtering mechanism represents an Intrinsic component integrated

The BioFragment Database (BFDb): An open-data platform for computational chemistry analysis of noncovalent interactions

Science.gov (United States)

Burns, Lori A.; Faver, John C.; Zheng, Zheng; Marshall, Michael S.; Smith, Daniel G. A.; Vanommeslaeghe, Kenno; MacKerell, Alexander D.; Merz, Kenneth M.; Sherrill, C. David

2017-10-01

Accurate potential energy models are necessary for reliable atomistic simulations of chemical phenomena. In the realm of biomolecular modeling, large systems like proteins comprise very many noncovalent interactions (NCIs) that can contribute to the protein's stability and structure. This work presents two high-quality chemical databases of common fragment interactions in biomolecular systems as extracted from high-resolution Protein DataBank crystal structures: 3380 sidechain-sidechain interactions and 100 backbone-backbone interactions that inaugurate the BioFragment Database (BFDb). Absolute interaction energies are generated with a computationally tractable explicitly correlated coupled cluster with perturbative triples [CCSD(T)-F12] "silver standard" (0.05 kcal/mol average error) for NCI that demands only a fraction of the cost of the conventional "gold standard," CCSD(T) at the complete basis set limit. By sampling extensively from biological environments, BFDb spans the natural diversity of protein NCI motifs and orientations. In addition to supplying a thorough assessment for lower scaling force-field (2), semi-empirical (3), density functional (244), and wavefunction (45) methods (comprising >1M interaction energies), BFDb provides interactive tools for running and manipulating the resulting large datasets and offers a valuable resource for potential energy model development and validation.

Understanding large social-ecological systems: introducing the SESMAD project

Directory of Open Access Journals (Sweden)

Michael Cox

2014-08-01

Full Text Available This article introduces the Social-ecological systems meta-analysis database (SESMAD project, which is the project behind the case studies and synthetic articles contained in this special issue of the International Journal of the Commons. SESMAD is an internationally collaborative meta-analysis project that builds on previous seminally synthetic work on small-scale common-pool resource systems conducted at the Workshop in Political Theory and Policy Analysis at Indiana University. This project is guided by the following research question: can the variables found to be important in explaining outcomes on small-scale systems be scaled up to explain outcomes in large-scale environmental governance? In this special issue we report on our findings thus far through a set of case studies of large-scale environmental governance, a paper that describes our conceptual advances, and a paper that compares these five case studies to further examine our central research question.

Hydraulic System Design of Hydraulic Actuators for Large Butterfly Valves

Directory of Open Access Journals (Sweden)

Ye HUANG

2014-09-01

Full Text Available Hydraulic control systems of butterfly valves are presently valve-controlled and pump-controlled. Valve-controlled hydraulic systems have serious power loss and generate much heat during throttling. Pump-controlled hydraulic systems have no overflow or throttling losses but are limited in the speed adjustment of the variable-displacement pump, generate much noise, pollute the environment, and have motor power that does not match load requirements, resulting in low efficiency under light loads and wearing of the variable-displacement pump. To overcome these shortcomings, this article designs a closed hydraulic control system in which an AC servo motor drives a quantitative pump that controls a spiral swinging hydraulic cylinder, and analyzes and calculates the structure and parameters of a spiral swinging hydraulic cylinder. The hydraulic system adjusts the servo motor’s speed according to the requirements of the control system, and the motor power matches the power provided to components, thus eliminating the throttling loss of hydraulic circuits. The system is compact, produces a large output force, provides stable transmission, has a quick response, and is suitable as a hydraulic control system of a large butterfly valve.

Biomolecular strategies for cell surface engineering

Science.gov (United States)

Wilson, John Tanner

Islet transplantation has emerged as a promising cell-based therapy for the treatment of diabetes, but its clinical efficacy remains limited by deleterious host responses that underlie islet destruction. In this dissertation, we describe the assembly of ultrathin conformal coatings that confer molecular-level control over the composition and biophysicochemical properties of the islet surface with implications for improving islet engraftment. Significantly, this work provides novel biomolecular strategies for cell surface engineering with broad biomedical and biotechnological applications in cell-based therapeutics and beyond. Encapsulation of cells and tissue offers a rational approach for attenuating deleterious host responses towards transplanted cells, but a need exists to develop cell encapsulation strategies that minimize transplant volume. Towards this end, we endeavored to generate nanothin films of diverse architecture with tunable properties on the extracellular surface of individual pancreatic islets through a process of layer-by-layer (LbL) self assembly. We first describe the formation of poly(ethylene glycol) (PEG)-rich conformal coatings on islets via LbL self assembly of poly(L-lysine)-g-PEG(biotin) and streptavidin. Multilayer thin films conformed to the geometrically and chemically heterogeneous islet surface, and could be assembled without loss of islet viability or function. Significantly, coated islets performed comparably to untreated controls in a murine model of allogenic intraportal islet transplantation, and, to our knowledge, this is the first study to report in vivo survival and function of nanoencapsulated cells or cell aggregates. Based on these findings, we next postulated that structurally similar PLL-g-PEG copolymers comprised of shorter PEG grafts might be used to initiate and propagate the assembly of polyelectrolyte multilayer (PEM) films on pancreatic islets, while simultaneously preserving islet viability. Through control of PLL

Security and VO management capabilities in a large-scale Grid operating system

OpenAIRE

Aziz, Benjamin; Sporea, Ioana

2014-01-01

This paper presents a number of security and VO management capabilities in a large-scale distributed Grid operating system. The capabilities formed the basis of the design and implementation of a number of security and VO management services in the system. The main aim of the paper is to provide some idea of the various functionality cases that need to be considered when designing similar large-scale systems in the future.

Customer Relationship Management Systems - Why Many Large Companies Do Not Have Them?

Science.gov (United States)

Cunha, Manuela; Varajão, João; Santana, Daniela; Bentes, Isabel

Today's information technologies are heavily embedded in the reality of organizations. Their role is essential not only at the level of internal processes optimization, but also the interaction between the company and its environment. In this context, the Customer Relationship Management (CRM) systems are powerful competitive tools in many different sectors of activity. Despite the undeniable importance of these systems, there are in practice, many large companies that do not use them. Supported by the results of a survey carried out in a sample of large enterprises, this paper seeks to answer to the research question "why many large companies do not have CRM systems".

An engineering design approach to systems biology.

Science.gov (United States)

Janes, Kevin A; Chandran, Preethi L; Ford, Roseanne M; Lazzara, Matthew J; Papin, Jason A; Peirce, Shayn M; Saucerman, Jeffrey J; Lauffenburger, Douglas A

2017-07-17

Measuring and modeling the integrated behavior of biomolecular-cellular networks is central to systems biology. Over several decades, systems biology has been shaped by quantitative biologists, physicists, mathematicians, and engineers in different ways. However, the basic and applied versions of systems biology are not typically distinguished, which blurs the separate aspirations of the field and its potential for real-world impact. Here, we articulate an engineering approach to systems biology, which applies educational philosophy, engineering design, and predictive models to solve contemporary problems in an age of biomedical Big Data. A concerted effort to train systems bioengineers will provide a versatile workforce capable of tackling the diverse challenges faced by the biotechnological and pharmaceutical sectors in a modern, information-dense economy.

The Unified Health System (SUS as a large technological system: territory, technique and politic

Directory of Open Access Journals (Sweden)

Luis Henrique Leandro Ribeiro

2018-03-01

Full Text Available The Uni ed Health System (SUS constitutes a large technological system wi- thin the Brazilian territory since it aggregates a broad and diverse materiality in organizing and managing its ows. Additionally, it has two other attributes that make it unique: high sensibility to speci cities of different places; and technical and political centralization and decentralization of its actions. The macro dimen- sion is the SUS, leading it to be understood not simply as a health system, through its: multidimensionality – elements of other life instances (social, economic, cul- tural and political; broad and unequal spectrum of actors (state and non-state who move it and the meanings of its actions; and the trans-scaleness of its con- cretion in places (local, national and international nexuses. As an infrastructure of everyday life, it is a hegemonic large technological system that acts upon objec- tive (technosphere and subjective (psychosphere conditions of existence, a con- ception that has important implications for health policy and territory integration.

A document preparation system in a large network environment

Energy Technology Data Exchange (ETDEWEB)

Vigil, M.; Bouchier, S.; Sanders, C.; Sydoriak, S.; Wheeler, K.

1988-01-01

At Los Alamos National Laboratory, we have developed an integrated document preparation system that produces publication-quality documents. This system combines text formatters and computer graphics capabilities that have been adapted to meet the needs of users in a large scientific research laboratory. This paper describes the integration of document processing technology to develop a system architecture, based on a page description language, to provide network-wide capabilities in a distributed computing environment. We describe the Laboratory requirements, the integration and implementation issues, and the challenges we faced developing this system.

Contractile injection systems of bacteriophages and related systems

DEFF Research Database (Denmark)

Taylor, Nicholas M I; van Raaij, Mark J; Leiman, Petr G

2018-01-01

Contractile tail bacteriophages, or myobacteriophages, use a sophisticated biomolecular structure to inject their genome into the bacterial host cell. This structure consists of a contractile sheath enveloping a rigid tube that is sharpened by a spike-shaped protein complex at its tip. The spike ...

Concept for a power system controller for large space electrical power systems

Science.gov (United States)

Lollar, L. F.; Lanier, J. R., Jr.; Graves, J. R.

1981-01-01

The development of technology for a fail-operatonal power system controller (PSC) utilizing microprocessor technology for managing the distribution and power processor subsystems of a large multi-kW space electrical power system is discussed. The specific functions which must be performed by the PSC, the best microprocessor available to do the job, and the feasibility, cost savings, and applications of a PSC were determined. A limited function breadboard version of a PSC was developed to demonstrate the concept and potential cost savings.

Optical interconnect for large-scale systems

Science.gov (United States)

Dress, William

2013-02-01

This paper presents a switchless, optical interconnect module that serves as a node in a network of identical distribution modules for large-scale systems. Thousands to millions of hosts or endpoints may be interconnected by a network of such modules, avoiding the need for multi-level switches. Several common network topologies are reviewed and their scaling properties assessed. The concept of message-flow routing is discussed in conjunction with the unique properties enabled by the optical distribution module where it is shown how top-down software control (global routing tables, spanning-tree algorithms) may be avoided.

Software quality assurance: in large scale and complex software-intensive systems

NARCIS (Netherlands)

Mistrik, I.; Soley, R.; Ali, N.; Grundy, J.; Tekinerdogan, B.

2015-01-01

Software Quality Assurance in Large Scale and Complex Software-intensive Systems presents novel and high-quality research related approaches that relate the quality of software architecture to system requirements, system architecture and enterprise-architecture, or software testing. Modern software

Pulsed rf systems for large storage rings

International Nuclear Information System (INIS)

Wilson, P.B.

1979-03-01

The possibility is considered that by using a pulsed rf system a substantial reduction can be made in the rf power requirement for the next generation of large storage rings. For a ring with a sufficiently large circumference, the time between bunch passages, T/sub b/, can exceed the cavity filling time, T/sub f/. As the ratio T/sub b//T/sub f/ increases, it is clear that at some point the average power requirement can be reduced by pulsing the rf to the cavities. In this mode of operation, the rf power is turned on a filling time or so before the arrival of a bunch and is switched off again at the time of bunch passage. There is no rf energy in the accelerating structure, and hence no power dissipation, for most of the period between bunches

Computer-based data acquisition system in the Large Coil Test Facility

International Nuclear Information System (INIS)

Gould, S.S.; Layman, L.R.; Million, D.L.

1983-01-01

The utilization of computers for data acquisition and control is of paramount importance on large-scale fusion experiments because they feature the ability to acquire data from a large number of sensors at various sample rates and provide for flexible data interpretation, presentation, reduction, and analysis. In the Large Coil Test Facility (LCTF) a Digital Equipment Corporation (DEC) PDP-11/60 host computer with the DEC RSX-11M operating system coordinates the activities of five DEC LSI-11/23 front-end processors (FEPs) via direct memory access (DMA) communication links. This provides host control of scheduled data acquisition and FEP event-triggered data collection tasks. Four of the five FEPs have no operating system

A remote joint system for large vacuum ducts

International Nuclear Information System (INIS)

Hagmann, D.B.; Coughlan, J.B.

1983-01-01

A large remote vacuum duct joining system has been developed for fusion machines that uses several two-jaw screwdriven clamps. The preferred location for clamp installation is inside the vacuum duct where access space is available for the actuating device. It also decreases space needed for handling operations exterior to the duct. The clamp system is unique in that it is low cost, applies force directly over the seal, permits leak testing to the seal annulus, is highly reliable, can be remotely replaced, and is usable on a variety of other applications

A convex optimization approach for solving large scale linear systems

Directory of Open Access Journals (Sweden)

Debora Cores

2017-01-01

Full Text Available The well-known Conjugate Gradient (CG method minimizes a strictly convex quadratic function for solving large-scale linear system of equations when the coefficient matrix is symmetric and positive definite. In this work we present and analyze a non-quadratic convex function for solving any large-scale linear system of equations regardless of the characteristics of the coefficient matrix. For finding the global minimizers, of this new convex function, any low-cost iterative optimization technique could be applied. In particular, we propose to use the low-cost globally convergent Spectral Projected Gradient (SPG method, which allow us to extend this optimization approach for solving consistent square and rectangular linear system, as well as linear feasibility problem, with and without convex constraints and with and without preconditioning strategies. Our numerical results indicate that the new scheme outperforms state-of-the-art iterative techniques for solving linear systems when the symmetric part of the coefficient matrix is indefinite, and also for solving linear feasibility problems.

Status and Future Developments in Large Accelerator Control Systems

International Nuclear Information System (INIS)

Karen S. White

2006-01-01

Over the years, accelerator control systems have evolved from small hardwired systems to complex computer controlled systems with many types of graphical user interfaces and electronic data processing. Today's control systems often include multiple software layers, hundreds of distributed processors, and hundreds of thousands of lines of code. While it is clear that the next generation of accelerators will require much bigger control systems, they will also need better systems. Advances in technology will be needed to ensure the network bandwidth and CPU power can provide reasonable update rates and support the requisite timing systems. Beyond the scaling problem, next generation systems face additional challenges due to growing cyber security threats and the likelihood that some degree of remote development and operation will be required. With a large number of components, the need for high reliability increases and commercial solutions can play a key role towards this goal. Future control systems will operate more complex machines and need to present a well integrated, interoperable set of tools with a high degree of automation. Consistency of data presentation and exception handling will contribute to efficient operations. From the development perspective, engineers will need to provide integrated data management in the beginning of the project and build adaptive software components around a central data repository. This will make the system maintainable and ensure consistency throughout the inevitable changes during the machine lifetime. Additionally, such a large project will require professional project management and disciplined use of well-defined engineering processes. Distributed project teams will make the use of standards, formal requirements and design and configuration control vital. Success in building the control system of the future may hinge on how well we integrate commercial components and learn from best practices used in other industries

Large Scale Emerging Properties from Non Hamiltonian Complex Systems

Directory of Open Access Journals (Sweden)

Marco Bianucci

2017-06-01

Full Text Available The concept of “large scale” depends obviously on the phenomenon we are interested in. For example, in the field of foundation of Thermodynamics from microscopic dynamics, the spatial and time large scales are order of fraction of millimetres and microseconds, respectively, or lesser, and are defined in relation to the spatial and time scales of the microscopic systems. In large scale oceanography or global climate dynamics problems the time scales of interest are order of thousands of kilometres, for space, and many years for time, and are compared to the local and daily/monthly times scales of atmosphere and ocean dynamics. In all the cases a Zwanzig projection approach is, at least in principle, an effective tool to obtain class of universal smooth “large scale” dynamics for few degrees of freedom of interest, starting from the complex dynamics of the whole (usually many degrees of freedom system. The projection approach leads to a very complex calculus with differential operators, that is drastically simplified when the basic dynamics of the system of interest is Hamiltonian, as it happens in Foundation of Thermodynamics problems. However, in geophysical Fluid Dynamics, Biology, and in most of the physical problems the building block fundamental equations of motions have a non Hamiltonian structure. Thus, to continue to apply the useful projection approach also in these cases, we exploit the generalization of the Hamiltonian formalism given by the Lie algebra of dissipative differential operators. In this way, we are able to analytically deal with the series of the differential operators stemming from the projection approach applied to these general cases. Then we shall apply this formalism to obtain some relevant results concerning the statistical properties of the El Niño Southern Oscillation (ENSO.

Large capacity, high-speed multiparameter multichannel analysis system

International Nuclear Information System (INIS)

Hendricks, R.W.; Seeger, P.A.; Scheer, J.W.; Suehiro, S.

1980-01-01

A data acquisition system for recording multiparameter digital data into a large memory array at over 2.5 MHz is described. The system consists of a MOSTEK MK8600 2048K x 24-bit memory system, I/O ports to various external devices including the CAMAC dataway, a memory incrementer/adder and a daisy-chain of experiment-specific modules which calculate the memory address which is to be incremented. The design of the daisy-chain permits multiple modules and provides for easy modification as experimental needs change. The system has been designed for use in multiparameter, multichannel analysis of high-speed data gathered by position-sensitive detectors at conventional and synchrotron x-ray sources as well as for fixed energy and time-of-flight diffraction at continuous and pulsed neutron sources

Separate Poles Mode for Large-Capacity HVDC System

Science.gov (United States)

Zhu, Lin; Gao, Qin

2017-05-01

This paper proposes a novel connection mode, separate poles mode (SPM), for large-capacity HVDC systems. The proposed mode focuses on the core issues of HVDC connection in interconnected power grids and principally aims at increasing effective electric distance between poles, which helps to mitigate the interaction problems between AC system and DC system. Receiving end of bipolar HVDC has been divided into different inverter stations under the mode, and thus significantly alleviates difficulties in power transmission and consumption of receiving-end AC grids. By investigating the changes of multi-feed short-circuit ratio (MISCR), finding that HVDC with SPM shows critical impacts upon itself and other HVDC systems with conventional connection mode, which demonstrates that SPM can make balance between MISCR increase and short-circuit current limit.

Two-level systems driven by large-amplitude fields

International Nuclear Information System (INIS)

Ashhab, S.; Johansson, J. R.; Zagoskin, A. M.; Nori, Franco

2007-01-01

We analyze the dynamics of a two-level system subject to driving by large-amplitude external fields, focusing on the resonance properties in the case of driving around the region of avoided level crossing. In particular, we consider three main questions that characterize resonance dynamics: (1) the resonance condition (2) the frequency of the resulting oscillations on resonance, and (3) the width of the resonance. We identify the regions of validity of different approximations. In a large region of the parameter space, we use a geometric picture in order to obtain both a simple understanding of the dynamics and quantitative results. The geometric approach is obtained by dividing the evolution into discrete time steps, with each time step described by either a phase shift on the basis states or a coherent mixing process corresponding to a Landau-Zener crossing. We compare the results of the geometric picture with those of a rotating wave approximation. We also comment briefly on the prospects of employing strong driving as a useful tool to manipulate two-level systems

SMPBS: Web server for computing biomolecular electrostatics using finite element solvers of size modified Poisson-Boltzmann equation.

Science.gov (United States)

Xie, Yang; Ying, Jinyong; Xie, Dexuan

2017-03-30

SMPBS (Size Modified Poisson-Boltzmann Solvers) is a web server for computing biomolecular electrostatics using finite element solvers of the size modified Poisson-Boltzmann equation (SMPBE). SMPBE not only reflects ionic size effects but also includes the classic Poisson-Boltzmann equation (PBE) as a special case. Thus, its web server is expected to have a broader range of applications than a PBE web server. SMPBS is designed with a dynamic, mobile-friendly user interface, and features easily accessible help text, asynchronous data submission, and an interactive, hardware-accelerated molecular visualization viewer based on the 3Dmol.js library. In particular, the viewer allows computed electrostatics to be directly mapped onto an irregular triangular mesh of a molecular surface. Due to this functionality and the fast SMPBE finite element solvers, the web server is very efficient in the calculation and visualization of electrostatics. In addition, SMPBE is reconstructed using a new objective electrostatic free energy, clearly showing that the electrostatics and ionic concentrations predicted by SMPBE are optimal in the sense of minimizing the objective electrostatic free energy. SMPBS is available at the URL: smpbs.math.uwm.edu © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Single Frequency Impedance Analysis on Reduced Graphene Oxide Screen-Printed Electrode for Biomolecular Detection.

Science.gov (United States)

Rajesh; Singal, Shobhita; Kotnala, Ravinder K

2017-10-01

A biofunctionalized reduced graphene oxide (rGO)-modified screen-printed carbon electrode (SPCE) was constructed as an immunosensor for C-reactive protein (CRP) detection, a biomarker released in early stage acute myocardial infarction. A different approach of single frequency analysis (SFA) study was utilized for the biomolecular sensing, by monitoring the response in phase angle changes obtained at an optimized frequency resulting from antigen-antibody interactions. A set of measurements were carried out to optimize a frequency where a maximum change in phase angle was observed, and in this case, we found it at around 10 Hz. The bioelectrode was characterized by contact angle measurements, scanning electron microscopy, and electrochemical techniques. A concentration-dependent response of immunosensor to CRP with the change in phase angle, at a fixed frequency of 10 Hz, was found to be in the range of 10 ng mL -1 to 10 μg mL -1 in PBS and was fit quantitative well with the Hill-Langmuir equation. Based on the concentration-response data, the dissociation constant (K d ) was found to be 3.5 nM (with a Hill coefficient n = 0.57), which indicated a negative cooperativity with high anti-CRP (antibody)-CRP (antigen) binding at the electrode surface. A low-frequency analysis of sensing with an ease of measurement on a disposable electroactive rGO-modified electrode with high selectivity and sensitivity makes it a potential tool for biological sensors.

Enhanced sampling algorithms.

Science.gov (United States)

Mitsutake, Ayori; Mori, Yoshiharu; Okamoto, Yuko

2013-01-01

In biomolecular systems (especially all-atom models) with many degrees of freedom such as proteins and nucleic acids, there exist an astronomically large number of local-minimum-energy states. Conventional simulations in the canonical ensemble are of little use, because they tend to get trapped in states of these energy local minima. Enhanced conformational sampling techniques are thus in great demand. A simulation in generalized ensemble performs a random walk in potential energy space and can overcome this difficulty. From only one simulation run, one can obtain canonical-ensemble averages of physical quantities as functions of temperature by the single-histogram and/or multiple-histogram reweighting techniques. In this article we review uses of the generalized-ensemble algorithms in biomolecular systems. Three well-known methods, namely, multicanonical algorithm, simulated tempering, and replica-exchange method, are described first. Both Monte Carlo and molecular dynamics versions of the algorithms are given. We then present various extensions of these three generalized-ensemble algorithms. The effectiveness of the methods is tested with short peptide and protein systems.

Participatory Design of Large-Scale Information Systems

DEFF Research Database (Denmark)

Simonsen, Jesper; Hertzum, Morten

2008-01-01

into a PD process model that (1) emphasizes PD experiments as transcending traditional prototyping by evaluating fully integrated systems exposed to real work practices; (2) incorporates improvisational change management including anticipated, emergent, and opportunity-based change; and (3) extends initial...... design and development into a sustained and ongoing stepwise implementation that constitutes an overall technology-driven organizational change. The process model is presented through a largescale PD experiment in the Danish healthcare sector. We reflect on our experiences from this experiment......In this article we discuss how to engage in large-scale information systems development by applying a participatory design (PD) approach that acknowledges the unique situated work practices conducted by the domain experts of modern organizations. We reconstruct the iterative prototyping approach...

Constructing large scale SCI-based processing systems by switch elements

International Nuclear Information System (INIS)

Wu, B.; Kristiansen, E.; Skaali, B.; Bogaerts, A.; Divia, R.; Mueller, H.

1993-05-01

The goal of this paper is to study some of the design criteria for the switch elements to form the interconnection of large scale SCI-based processing systems. The approved IEEE standard 1596 makes it possible to couple up to 64K nodes together. In order to connect thousands of nodes to construct large scale SCI-based processing systems, one has to interconnect these nodes by switch elements to form different topologies. A summary of the requirements and key points of interconnection networks and switches is presented. Two models of the SCI switch elements are proposed. The authors investigate several examples of systems constructed for 4-switches with simulations and the results are analyzed. Some issues and enhancements are discussed to provide the ideas behind the switch design that can improve performance and reduce latency. 29 refs., 11 figs., 3 tabs

Tool Support for Parametric Analysis of Large Software Simulation Systems

Science.gov (United States)

Schumann, Johann; Gundy-Burlet, Karen; Pasareanu, Corina; Menzies, Tim; Barrett, Tony

2008-01-01

The analysis of large and complex parameterized software systems, e.g., systems simulation in aerospace, is very complicated and time-consuming due to the large parameter space, and the complex, highly coupled nonlinear nature of the different system components. Thus, such systems are generally validated only in regions local to anticipated operating points rather than through characterization of the entire feasible operational envelope of the system. We have addressed the factors deterring such an analysis with a tool to support envelope assessment: we utilize a combination of advanced Monte Carlo generation with n-factor combinatorial parameter variations to limit the number of cases, but still explore important interactions in the parameter space in a systematic fashion. Additional test-cases, automatically generated from models (e.g., UML, Simulink, Stateflow) improve the coverage. The distributed test runs of the software system produce vast amounts of data, making manual analysis impossible. Our tool automatically analyzes the generated data through a combination of unsupervised Bayesian clustering techniques (AutoBayes) and supervised learning of critical parameter ranges using the treatment learner TAR3. The tool has been developed around the Trick simulation environment, which is widely used within NASA. We will present this tool with a GN&C (Guidance, Navigation and Control) simulation of a small satellite system.

Large Time Behavior of the Vlasov-Poisson-Boltzmann System

Directory of Open Access Journals (Sweden)

Li Li

2013-01-01

Full Text Available The motion of dilute charged particles can be modeled by Vlasov-Poisson-Boltzmann system. We study the large time stability of the VPB system. To be precise, we prove that when time goes to infinity, the solution of VPB system tends to global Maxwellian state in a rate Ot−∞, by using a method developed for Boltzmann equation without force in the work of Desvillettes and Villani (2005. The improvement of the present paper is the removal of condition on parameter λ as in the work of Li (2008.

Large-scale digitizer system, analog converters

International Nuclear Information System (INIS)

Althaus, R.F.; Lee, K.L.; Kirsten, F.A.; Wagner, L.J.

1976-10-01

Analog to digital converter circuits that are based on the sharing of common resources, including those which are critical to the linearity and stability of the individual channels, are described. Simplicity of circuit composition is valued over other more costly approaches. These are intended to be applied in a large-scale processing and digitizing system for use with high-energy physics detectors such as drift-chambers or phototube-scintillator arrays. Signal distribution techniques are of paramount importance in maintaining adequate signal-to-noise ratio. Noise in both amplitude and time-jitter senses is held sufficiently low so that conversions with 10-bit charge resolution and 12-bit time resolution are achieved

Very Large Data Volumes Analysis of Collaborative Systems with Finite Number of States

Science.gov (United States)

Ivan, Ion; Ciurea, Cristian; Pavel, Sorin

2010-01-01

The collaborative system with finite number of states is defined. A very large database is structured. Operations on large databases are identified. Repetitive procedures for collaborative systems operations are derived. The efficiency of such procedures is analyzed. (Contains 6 tables, 5 footnotes and 3 figures.)

Solid-state NMR spectroscopy on complex biomolecules

NARCIS (Netherlands)

Renault, M.A.M.; Cukkemane, A.A.; Baldus, M.

2010-01-01

Biomolecular applications of NMR spectroscopy are often merely associated with soluble molecules or magnetic resonance imaging. However, since the late 1970s, solid-state NMR (ssNMR) spectroscopy has demonstrated its ability to provide atomic-level insight into complex biomolecular systems ranging

Transformations of large technical systems : a multi-level analysis of the Dutch highway system (1950-2000)

NARCIS (Netherlands)

Geels, F.W.

2007-01-01

The transformation of existing systems is an underexposed topic in large technical systems (LTS) research. Most LTS research has focused on the emergence and stabilization of systems, ending with momentum. But how is momentum overcome, and how do transformations come about? This article presents a

Turbomolecular pump vacuum system for the Princeton Large Torus

International Nuclear Information System (INIS)

Dylla, H.F.

1977-10-01

A turbomolecular pump vacuum system has been designed and installed on the Princeton Large Torus (PLT). Four vertical shaft, oil-bearing, 1500 l/s turbomolecular pumps have been interfaced to the 6400 liter PLT Vacuum vessel to provide a net pumping speed of 3000 l/s for H 2 . The particular requirements and problems of tokamak vacuum systems are enumerated. A vacuum control system is described which protects the vacuum vessel from contamination, and protects the turbomolecular pumps from damage under a variety of possible failure modes. The performance of the vacuum system is presented in terms of pumping speed measurements and residual gas behavior

Research and development of system to utilize photovoltaic energy. Study on large-scale PV power supply system; Taiyoko hatsuden riyo system no kenkyu kaihatsu. Taiyo energy kyokyu system no chosa kenkyu

Energy Technology Data Exchange (ETDEWEB)

Tatsuta, M [New Energy and Industrial Technology Development Organization, Tokyo (Japan)

1994-12-01

This paper reports the study results on large-scale PV power supply systems in fiscal 1994. (1) On optimization of large-scale systems, the conceptual design of the model system was carried out which supposes a large-scale integrated PV power generation system in desert area. As a result, a pair of 250kW generation system was designed as minimum one consisting power unit. Its frame and construction method were designed considering weather conditions in the inland of China. (2) On optimization of large-scale transmission systems, as large-scale power transmission systems for PV power generation, the following were studied: AC aerial transmission, DC aerial transmission, superconducting transmission, hydrogen gas pipeline, and LH2 tanker transport. (3) On the influence of large-scale systems, it was estimated that emission control is expected by substituting PV power generation for coal fired power generation, the negative influence on natural environment cannot be supposed, and the favorable economic effect is expected as influence on social environment. 4 tabs.

Value of flexibility in systems with large wind penetration

OpenAIRE

Silva , Vera

2010-01-01

The focus of this thesis is the quantification of the value of operation flexibility in systems with large penetration of wind generation. This begins with the quantification of the impact of wind generation (WG) uncertainty on the system's needs for frequency regulation and reserve. This is done by combing the stochastic behaviour of wind generation, demand uncertainty and generation outages. Two different approaches are compared to access the implications of using normal distribution approx...

Modeling and power system stability of VSC-HVDC systems for grid-connection of large offshore windfarms

Energy Technology Data Exchange (ETDEWEB)

Xue Yijing [Vestas China, Beijing (China); Akhmatov, Vladislav [Technical Univ. of Denmark, Lyngby (Denmark). Centre for Electric Technology

2009-07-01

Utilization of Voltage Source Converter (VSC) - High Voltage Direct Current (HVDC) systems for grid-connection of large offshore windfarms becomes relevant as installed power capacities as well as distances to the connection points of on-land transmission systems increase. At the same time, the grid code requirements of the Transmission System Operators (TSO), including ancillary system services and Low-Voltage Fault-Ride-Through (LVFRT) capability of large offshore windfarms, become more demanding. This paper presents a general-level model of and a LVFRT solution for a VSC-HVDC system for grid-connection of large offshore windfarms. The VSC-HVDC model is implemented using a general approach of independent control of active and reactive power in normal operations. The on-land VSC inverter, i.e. a grid-side inverter, provides voltage support to the transmission system and comprises a LVFRT solution in short-circuit faults. The presented model, LVFRT solution and impact on the system stability are investigated as a case study of a 1,000 MW offshore windfarm grid-connected through a VSC-HVDC system. The investigation is carried out on a model of the west Danish, with some elements of the north German, 400 kV, 220 kV and 150 kV transmission systems stage 2005-2006 using the DIgSILENT PowerFactory simulation program. In the investigation, a thermal power plant just south to the Danish border has been substituted by this 1,000 MW offshore windfarm utilizing the VSC-HVDC system. The investigation has shown that the substitution of a thermal power plant by a VSC-HVDC connected offshore windfarm should not have any negative impact on the short-term stability of the west Danish transmission system. The investigation should be repeated applying updated system model stages and offshore wind power commissioning schedules in the North and Baltic Seas. (orig.)

Solution methods for large systems of linear equations in BACCHUS

International Nuclear Information System (INIS)

Homann, C.; Dorr, B.

1993-05-01

The computer programme BACCHUS is used to describe steady state and transient thermal-hydraulic behaviour of a coolant in a fuel element with intact geometry in a fast breeder reactor. In such computer programmes generally large systems of linear equations with sparse matrices of coefficients, resulting from discretization of coolant conservation equations, must be solved thousands of times giving rise to large demands of main storage and CPU time. Direct and iterative solution methods of the systems of linear equations, available in BACCHUS, are described, giving theoretical details and experience with their use in the programme. Besides use of a method of lines, a Runge-Kutta-method, for solution of the partial differential equation is outlined. (orig.) [de

Parameter and State Estimation of Large-Scale Complex Systems Using Python Tools

Directory of Open Access Journals (Sweden)

M. Anushka S. Perera

2015-07-01

Full Text Available This paper discusses the topics related to automating parameter, disturbance and state estimation analysis of large-scale complex nonlinear dynamic systems using free programming tools. For large-scale complex systems, before implementing any state estimator, the system should be analyzed for structural observability and the structural observability analysis can be automated using Modelica and Python. As a result of structural observability analysis, the system may be decomposed into subsystems where some of them may be observable --- with respect to parameter, disturbances, and states --- while some may not. The state estimation process is carried out for those observable subsystems and the optimum number of additional measurements are prescribed for unobservable subsystems to make them observable. In this paper, an industrial case study is considered: the copper production process at Glencore Nikkelverk, Kristiansand, Norway. The copper production process is a large-scale complex system. It is shown how to implement various state estimators, in Python, to estimate parameters and disturbances, in addition to states, based on available measurements.

Reliable pipeline repair system for very large pipe size

Energy Technology Data Exchange (ETDEWEB)

Charalambides, John N.; Sousa, Alexandre Barreto de [Oceaneering International, Inc., Houston, TX (United States)

2004-07-01

The oil and gas industry worldwide has been mainly depending on the long-term reliability of rigid pipelines to ensure the transportation of hydrocarbons, crude oil, gas, fuel, etc. Many other methods are also utilized onshore and offshore (e.g. flexible lines, FPSO's, etc.), but when it comes to the underwater transportation of very high volumes of oil and gas, the industry commonly uses large size rigid pipelines (i.e. steel pipes). Oil and gas operators learned to depend on the long-lasting integrity of these very large pipelines and many times they forget or disregard that even steel pipelines degrade over time and more often that that, they are also susceptible to various forms of damage (minor or major, environmental or external, etc.). Over the recent years the industry had recognized the need of implementing an 'emergency repair plan' to account for such unforeseen events and the oil and gas operators have become 'smarter' by being 'pro-active' in order to ensure 'flow assurance'. When we consider very large diameter steel pipelines such as 42' and 48' nominal pipe size (NPS), the industry worldwide does not provide 'ready-made', 'off-the-shelf' repair hardware that can be easily shipped to the offshore location and effect a major repair within acceptable time frames and avoid substantial profit losses due to 'down-time' in production. The typical time required to establish a solid repair system for large pipe diameters could be as long as six or more months (depending on the availability of raw materials). This paper will present in detail the Emergency Pipeline Repair Systems (EPRS) that Oceaneering successfully designed, manufactured, tested and provided to two major oil and gas operators, located in two different continents (Gulf of Mexico, U.S.A. and Arabian Gulf, U.A.E.), for two different very large pipe sizes (42'' and 48'' Nominal Pipe Sizes

A new system of labour management in African large-scale agriculture?

DEFF Research Database (Denmark)

Gibbon, Peter; Riisgaard, Lone

2014-01-01

This paper applies a convention theory (CT) approach to the analysis of labour management systems in African large-scale farming. The reconstruction of previous analyses of high-value crop production on large-scale farms in Africa in terms of CT suggests that, since 1980–95, labour management has...

The role of the innate immune system in Alzheimer's disease and frontotemporal lobar degeneration: an eye on microglia.

Science.gov (United States)

Ridolfi, Elisa; Barone, Cinzia; Scarpini, Elio; Galimberti, Daniela

2013-01-01

In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

Large-scale gene function analysis with the PANTHER classification system.

Science.gov (United States)

Mi, Huaiyu; Muruganujan, Anushya; Casagrande, John T; Thomas, Paul D

2013-08-01

The PANTHER (protein annotation through evolutionary relationship) classification system (http://www.pantherdb.org/) is a comprehensive system that combines gene function, ontology, pathways and statistical analysis tools that enable biologists to analyze large-scale, genome-wide data from sequencing, proteomics or gene expression experiments. The system is built with 82 complete genomes organized into gene families and subfamilies, and their evolutionary relationships are captured in phylogenetic trees, multiple sequence alignments and statistical models (hidden Markov models or HMMs). Genes are classified according to their function in several different ways: families and subfamilies are annotated with ontology terms (Gene Ontology (GO) and PANTHER protein class), and sequences are assigned to PANTHER pathways. The PANTHER website includes a suite of tools that enable users to browse and query gene functions, and to analyze large-scale experimental data with a number of statistical tests. It is widely used by bench scientists, bioinformaticians, computer scientists and systems biologists. In the 2013 release of PANTHER (v.8.0), in addition to an update of the data content, we redesigned the website interface to improve both user experience and the system's analytical capability. This protocol provides a detailed description of how to analyze genome-wide experimental data with the PANTHER classification system.

Secure File Allocation and Caching in Large-scale Distributed Systems

DEFF Research Database (Denmark)

Di Mauro, Alessio; Mei, Alessandro; Jajodia, Sushil

2012-01-01

In this paper, we present a file allocation and caching scheme that guarantees high assurance, availability, and load balancing in a large-scale distributed file system that can support dynamic updates of authorization policies. The scheme uses fragmentation and replication to store files with hi......-balancing, and reducing delay of read operations. The system offers a trade-off-between performance and security that is dynamically tunable according to the current level of threat. We validate our mechanisms with extensive simulations in an Internet-like network.......In this paper, we present a file allocation and caching scheme that guarantees high assurance, availability, and load balancing in a large-scale distributed file system that can support dynamic updates of authorization policies. The scheme uses fragmentation and replication to store files with high...... security requirements in a system composed of a majority of low-security servers. We develop mechanisms to fragment files, to allocate them into multiple servers, and to cache them as close as possible to their readers while preserving the security requirement of the files, providing load...

Large solar heating system with seasonal storage for buld drying in Lisse, the Netherlands

NARCIS (Netherlands)

Bokhoven, T.P.; Geus, A.C. de

1996-01-01

Within IEA Task 14 (Advanced Solar Systems) of the IEA Solar Heating and Cooling Programme a working group was established dealing with large advanced solar energy systems (the Large Systems Working group). The goal of this working group was to generate a common base of experiences for the design

Universality in few-body systems with large scattering length

International Nuclear Information System (INIS)

Hammer, H.-W.

2005-01-01

Effective Field Theory (EFT) provides a powerful framework that exploits a separation of scales in physical systems to perform systematically improvable, model-independent calculations. Particularly interesting are few-body systems with short-range interactions and large two-body scattering length. Such systems display remarkable universal features. In systems with more than two particles, a three-body force with limit cycle behavior is required for consistent renormalization already at leading order. We will review this EFT and some of its applications in the physics of cold atoms and nuclear physics. In particular, we will discuss the possibility of an infrared limit cycle in QCD. Recent extensions of the EFT approach to the four-body system and N-boson droplets in two spatial dimensions will also be addressed

Energy Decomposition Analysis Based on Absolutely Localized Molecular Orbitals for Large-Scale Density Functional Theory Calculations in Drug Design.

Science.gov (United States)

Phipps, M J S; Fox, T; Tautermann, C S; Skylaris, C-K

2016-07-12

We report the development and implementation of an energy decomposition analysis (EDA) scheme in the ONETEP linear-scaling electronic structure package. Our approach is hybrid as it combines the localized molecular orbital EDA (Su, P.; Li, H. J. Chem. Phys., 2009, 131, 014102) and the absolutely localized molecular orbital EDA (Khaliullin, R. Z.; et al. J. Phys. Chem. A, 2007, 111, 8753-8765) to partition the intermolecular interaction energy into chemically distinct components (electrostatic, exchange, correlation, Pauli repulsion, polarization, and charge transfer). Limitations shared in EDA approaches such as the issue of basis set dependence in polarization and charge transfer are discussed, and a remedy to this problem is proposed that exploits the strictly localized property of the ONETEP orbitals. Our method is validated on a range of complexes with interactions relevant to drug design. We demonstrate the capabilities for large-scale calculations with our approach on complexes of thrombin with an inhibitor comprised of up to 4975 atoms. Given the capability of ONETEP for large-scale calculations, such as on entire proteins, we expect that our EDA scheme can be applied in a large range of biomolecular problems, especially in the context of drug design.

Axiomatic design in large systems complex products, buildings and manufacturing systems

CERN Document Server

Suh, Nam

2016-01-01

This book provides a synthesis of recent developments in Axiomatic Design theory and its application in large complex systems. Introductory chapters provide concise tutorial materials for graduate students and new practitioners, presenting the fundamentals of Axiomatic Design and relating its key concepts to those of model-based systems engineering. A mathematical exposition of design axioms is also provided. The main body of the book, which represents a concentrated treatment of several applications, is divided into three parts covering work on: complex products; buildings; and manufacturing systems. The book shows how design work in these areas can benefit from the scientific and systematic underpinning provided by Axiomatic Design, and in so doing effectively combines the state of the art in design research with practice. All contributions were written by an international group of leading proponents of Axiomatic Design. The book concludes with a call to action motivating further research into the engineeri...

Economic Model Predictive Control for Large-Scale and Distributed Energy Systems

DEFF Research Database (Denmark)

Standardi, Laura

Sources (RESs) in the smart grids is increasing. These energy sources bring uncertainty to the production due to their fluctuations. Hence,smart grids need suitable control systems that are able to continuously balance power production and consumption.  We apply the Economic Model Predictive Control (EMPC......) strategy to optimise the economic performances of the energy systems and to balance the power production and consumption. In the case of large-scale energy systems, the electrical grid connects a high number of power units. Because of this, the related control problem involves a high number of variables......In this thesis, we consider control strategies for large and distributed energy systems that are important for the implementation of smart grid technologies.  An electrical grid has to ensure reliability and avoid long-term interruptions in the power supply. Moreover, the share of Renewable Energy...

Magnetic Properties of Large-Scale Nanostructured Graphene Systems

DEFF Research Database (Denmark)

Gregersen, Søren Schou

The on-going progress in two-dimensional (2D) materials and nanostructure fabrication motivates the study of altered and combined materials. Graphene—the most studied material of the 2D family—displays unique electronic and spintronic properties. Exceptionally high electron mobilities, that surpass...... those in conventional materials such as silicon, make graphene a very interesting material for high-speed electronics. Simultaneously, long spin-diffusion lengths and spin-life times makes graphene an eligible spin-transport channel. In this thesis, we explore fundamental features of nanostructured...... graphene systems using large-scale modeling techniques. Graphene perforations, or antidots, have received substantial interest in the prospect of opening large band gaps in the otherwise gapless graphene. Motivated by recent improvements of fabrication processes, such as forming graphene antidots and layer...

Exchanging large data object in multi-agent systems

Science.gov (United States)

Al-Yaseen, Wathiq Laftah; Othman, Zulaiha Ali; Nazri, Mohd Zakree Ahmad

2016-08-01

One of the Business Intelligent solutions that is currently in use is the Multi-Agent System (MAS). Communication is one of the most important elements in MAS, especially for exchanging large low level data between distributed agents (physically). The Agent Communication Language in JADE has been offered as a secure method for sending data, whereby the data is defined as an object. However, the object cannot be used to send data to another agent in a different location. Therefore, the aim of this paper was to propose a method for the exchange of large low level data as an object by creating a proxy agent known as a Delivery Agent, which temporarily imitates the Receiver Agent. The results showed that the proposed method is able to send large-sized data. The experiments were conducted using 16 datasets ranging from 100,000 to 7 million instances. However, for the proposed method, the RAM and the CPU machine had to be slightly increased for the Receiver Agent, but the latency time was not significantly different compared to the use of the Java Socket method (non-agent and less secure). With such results, it was concluded that the proposed method can be used to securely send large data between agents.

Development of large scale wind energy conservation system. Development of large scale wind energy conversion system; Ogata furyoku hatsuden system no kaihatsu. Ogata furyoku hatsuden system no kaihatsu

Energy Technology Data Exchange (ETDEWEB)

Takita, M [New Energy and Industrial Technology Development Organization, Tokyo (Japan)

1994-12-01

Described herein are the results of the FY1994 research program for development of large scale wind energy conversion system. The study on technological development of key components evaluates performance of, and confirms reliability and applicability of, hydraulic systems centered by those equipped with variable pitch mechanisms and electrohydraulic servo valves that control them. The study on blade conducts fatigue and crack-propagation tests, which show that the blades developed have high strength. The study on speed-increasing gear conducts load tests, confirming the effects of reducing vibration and noise by modification of the gear teeth. The study on NACELLE cover conducts vibration tests to confirm its vibration characteristics, and analyzes three-dimensional vibration by the finite element method. Some components for a 500kW commercial wind mill are fabricated, including rotor heads, variable pitch mechanisms, speed-increasing gears, YAW systems, and hydraulic control systems. The others fabricated include a remote supervisory control system for maintenance, system to integrate the wind mill into a power system, and electrical control devices in which site conditions, such as atmospheric temperature and lightening, are taken into consideration.

Nonterrestrial material processing and manufacturing of large space systems

Science.gov (United States)

Von Tiesenhausen, G.

1979-01-01

Nonterrestrial processing of materials and manufacturing of large space system components from preprocessed lunar materials at a manufacturing site in space is described. Lunar materials mined and preprocessed at the lunar resource complex will be flown to the space manufacturing facility (SMF), where together with supplementary terrestrial materials, they will be final processed and fabricated into space communication systems, solar cell blankets, radio frequency generators, and electrical equipment. Satellite Power System (SPS) material requirements and lunar material availability and utilization are detailed, and the SMF processing, refining, fabricating facilities, material flow and manpower requirements are described.

An interactive display system for large-scale 3D models

Science.gov (United States)

Liu, Zijian; Sun, Kun; Tao, Wenbing; Liu, Liman

2018-04-01

With the improvement of 3D reconstruction theory and the rapid development of computer hardware technology, the reconstructed 3D models are enlarging in scale and increasing in complexity. Models with tens of thousands of 3D points or triangular meshes are common in practical applications. Due to storage and computing power limitation, it is difficult to achieve real-time display and interaction with large scale 3D models for some common 3D display software, such as MeshLab. In this paper, we propose a display system for large-scale 3D scene models. We construct the LOD (Levels of Detail) model of the reconstructed 3D scene in advance, and then use an out-of-core view-dependent multi-resolution rendering scheme to realize the real-time display of the large-scale 3D model. With the proposed method, our display system is able to render in real time while roaming in the reconstructed scene and 3D camera poses can also be displayed. Furthermore, the memory consumption can be significantly decreased via internal and external memory exchange mechanism, so that it is possible to display a large scale reconstructed scene with over millions of 3D points or triangular meshes in a regular PC with only 4GB RAM.

Does reintroducing large wood influence the hydraulic landscape of a lowland river system?

Science.gov (United States)

Matheson, Adrian; Thoms, Martin; Reid, Michael

2017-09-01

Our understanding of the effectiveness of reintroduced large wood for restoration is largely based on studies from high energy river systems. By contrast, few studies of the effectiveness of reintroducing large wood have been undertaken on large, low energy, lowland river systems: river systems where large wood is a significant physical feature on the in-channel environment. This study investigated the effect of reintroduced large wood on the hydraulic landscape of the Barwon-Darling River, Australia, at low flows. To achieve this, the study compared three hydraulic landscapes of replicated reference (naturally wooded), control (unwooded,) and managed (wood reintroduced) treatments on three low flow periods. These time periods were prior to the reintroduction of large wood to managed reaches; several months after the reintroduction of large wood into the managed reaches; and then more than four years after wood reintroduction following several large flood events. Hydraulic landscapes of reaches were characterised using a range of spatial measures calculated from velocity measurements taken with a boat-mounted Acoustic Doppler Profiler. We hypothesised that reintroduced large wood would increase the diversity of the hydraulic landscape at low flows and that managed reaches would be more similar to the reference reaches. Our results suggest that the reintroduction of large wood did not significantly change the character of the hydraulic landscape at the reach scale after several months (p = 0.16) or several years (p = 0.29). Overall, the character of the hydraulic landscape in the managed reaches was more similar to the hydraulic landscape of the control reaches than the hydraulic landscape of the reference reaches, at low flows. Some variability in the hydraulic landscapes was detected over time, and this may reflect reworking of riverbed sediments and sensitivity to variation in discharge. The lack of a response in the low flow hydraulic landscape to the

A Study on Developing and Refining a Large Citation Service System

Directory of Open Access Journals (Sweden)

Kwang-Young Kim

2013-06-01

Full Text Available Today, citation index information is used as an outcome scale of spreading technology and encouraging research. Article citation information is an important factor to determine the authority of the relevant author. Google Scholar uses the article citation information to organize academic article search results with a rank algorithm. For an accurate analysis of such important citation index information, large amounts of bibliographic data are required. Therefore, this study aims to build a fast and efficient system for large amounts of bibliographic data, and to design and develop a system for quickly analyzing cited information for that data. This study also aims to use and analyze citation data to be a basic element for providing various advanced services to the academic article search system.

Solving large scale unit dilemma in electricity system by applying commutative law

Science.gov (United States)

Legino, Supriadi; Arianto, Rakhmat

2018-03-01

The conventional system, pooling resources with large centralized power plant interconnected as a network. provides a lot of advantages compare to the isolated one include optimizing efficiency and reliability. However, such a large plant need a huge capital. In addition, more problems emerged to hinder the construction of big power plant as well as its associated transmission lines. By applying commutative law of math, ab = ba, for all a,b €-R, the problem associated with conventional system as depicted above, can be reduced. The idea of having small unit but many power plants, namely “Listrik Kerakyatan,” abbreviated as LK provides both social and environmental benefit that could be capitalized by using proper assumption. This study compares the cost and benefit of LK to those of conventional system, using simulation method to prove that LK offers alternative solution to answer many problems associated with the large system. Commutative Law of Algebra can be used as a simple mathematical model to analyze whether the LK system as an eco-friendly distributed generation can be applied to solve various problems associated with a large scale conventional system. The result of simulation shows that LK provides more value if its plants operate in less than 11 hours as peaker power plant or load follower power plant to improve load curve balance of the power system. The result of simulation indicates that the investment cost of LK plant should be optimized in order to minimize the plant investment cost. This study indicates that the benefit of economies of scale principle does not always apply to every condition, particularly if the portion of intangible cost and benefit is relatively high.

The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

Directory of Open Access Journals (Sweden)

Elisa Ridolfi

2013-01-01

Full Text Available In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD and frontotemporal lobar degeneration (FTLD have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS. They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

Study of multi-functional precision optical measuring system for large scale equipment

Science.gov (United States)

Jiang, Wei; Lao, Dabao; Zhou, Weihu; Zhang, Wenying; Jiang, Xingjian; Wang, Yongxi

2017-10-01

The effective application of high performance measurement technology can greatly improve the large-scale equipment manufacturing ability. Therefore, the geometric parameters measurement, such as size, attitude and position, requires the measurement system with high precision, multi-function, portability and other characteristics. However, the existing measuring instruments, such as laser tracker, total station, photogrammetry system, mostly has single function, station moving and other shortcomings. Laser tracker needs to work with cooperative target, but it can hardly meet the requirement of measurement in extreme environment. Total station is mainly used for outdoor surveying and mapping, it is hard to achieve the demand of accuracy in industrial measurement. Photogrammetry system can achieve a wide range of multi-point measurement, but the measuring range is limited and need to repeatedly move station. The paper presents a non-contact opto-electronic measuring instrument, not only it can work by scanning the measurement path but also measuring the cooperative target by tracking measurement. The system is based on some key technologies, such as absolute distance measurement, two-dimensional angle measurement, automatically target recognition and accurate aiming, precision control, assembly of complex mechanical system and multi-functional 3D visualization software. Among them, the absolute distance measurement module ensures measurement with high accuracy, and the twodimensional angle measuring module provides precision angle measurement. The system is suitable for the case of noncontact measurement of large-scale equipment, it can ensure the quality and performance of large-scale equipment throughout the process of manufacturing and improve the manufacturing ability of large-scale and high-end equipment.

Condensed matter physics of biomolecule systems in a differential geometric framework

DEFF Research Database (Denmark)

Bohr, Henrik; Ipsen, J. H.; Markvorsen, Steen

2007-01-01

In this contribution biomolecular systems are analyzed in a framework of differential geometry in order to derive important condensed matter physics information. In the first section lipid bi-layer membranes are examined with respect to statistical properties and topology, e.g. a relation between...... vesicle formation and the proliferation of genus number. In the second section differential geometric methods are used for analyzing the surface structure of proteins and thereby understanding catalytic properties of larger proteins....

Condensed matter physics of biomolecule systems in a differential geometric framework

DEFF Research Database (Denmark)

Bohr, H.; Ipsen, John Hjort; Markvorsen, S

2007-01-01

In this contribution biomolecular systems are analyzed in a framework of differential geometry in order to derive important condensed matter physics information. In the first section lipid bi-layer membranes axe examined with respect to statistical properties and topology, e.g. a relation between...... vesicle formation and the proliferation of genus number. In the second section differential geometric methods are used for analyzing the surface structure of proteins and thereby understanding catalytic properties of larger proteins....

Quench detection system of the EURATOM coil for the Large Coil Task

International Nuclear Information System (INIS)

Noether, G.; Gauss, S.; Maurer, W.; Siewerdt, L.; Ulbricht, A.; Wuechner, F.

1989-01-01

A special quench detection system has been developed for the EURATOM Large Coil Task (LCT) coil. The system is based on a bridge circuit which uses a special 'two in hand' winding technique for the pancakes of the EURATOM LCT coil. The electronic circuit was designed in a fail safe way to prevent failure of the quench detector due to failure of one of its components. A method for quick balancing of the quench detection system in a large toroidal magnet system was applied. The quench detection system worked very reliably during the experimental phase of the LCT and was within the quench detection level setting of 50 mV, i.e. the system was not sensitive to poloidal field transients at or below this level. Non-electrical methods for quench detection were also investigated. (author)

Real-Time, Label-Free Detection of Biomolecular Interactions in Sandwich Assays by the Oblique-Incidence Reflectivity Difference Technique

Directory of Open Access Journals (Sweden)

Yung-Shin Sun

2014-12-01

Full Text Available One of the most important goals in proteomics is to detect the real-time kinetics of diverse biomolecular interactions. Fluorescence, which requires extrinsic tags, is a commonly and widely used method because of its high convenience and sensitivity. However, in order to maintain the conformational and functional integrality of biomolecules, label-free detection methods are highly under demand. We have developed the oblique-incidence reflectivity difference (OI-RD technique for label-free, kinetic measurements of protein-biomolecule interactions. Incorporating the total internal refection geometry into the OI-RD technique, we are able to detect as low as 0.1% of a protein monolayer, and this sensitivity is comparable with other label-free techniques such as surface plasmon resonance (SPR. The unique advantage of OI-RD over SPR is no need for dielectric layers. Moreover, using a photodiode array as the detector enables multi-channel detection and also eliminates the over-time signal drift. In this paper, we demonstrate the applicability and feasibility of the OI-RD technique by measuring the kinetics of protein-protein and protein-small molecule interactions in sandwich assays.

Preliminary results from a novel CVD diamond detector system for molecular imaging applications

International Nuclear Information System (INIS)

Mahon, A.R.

1996-01-01

A novel biomolecular imaging system incorporating a Chemical Vapour Deposition diamond detector is in development. The synthetic diamond is used as a UV detector to image nucleic acids in electrophoresis gels. The microstrip diamond detector currently has a spatial resolution of 30 μm. Preliminary results are presented which include: QE measurements of diamond detectors, detector time response, detector UV response and current detection limits of biomolecules in gel. The potential applications of the technology, and its significant advantages in speed and sensitivity over the current systems are discussed

In situ, accurate, surface-enhanced Raman scattering detection of cancer cell nucleus with synchronous location by an alkyne-labeled biomolecular probe.

Science.gov (United States)

Zhang, Jing; Liang, Lijia; Guan, Xin; Deng, Rong; Qu, Huixin; Huang, Dianshuai; Xu, Shuping; Liang, Chongyang; Xu, Weiqing

2018-01-01

A surface-enhanced Raman scattering (SERS) method for in situ detection and analysis of the intranuclear biomolecular information of a cell has been developed based on a small, biocompatible, nuclear-targeting alkyne-tagged deoxyribonucleic acid (DNA) probe (5-ethynyl-2'-deoxyuridine, EDU) that can specially accumulate in the cell nucleus during DNA replications to precisely locate the nuclear region without disturbance in cell biological activities and functions. Since the specific alkyne group shows a Raman peak in the Raman-silent region of cells, it is an interior label to visualize the nuclear location synchronously in real time when measuring the SERS spectra of a cell. Because no fluorescent-labeled dyes were used for locating cell nuclei, this method is simple, nondestructive, non- photobleaching, and valuable for the in situ exploration of vital physiological processes with DNA participation in cell organelles. Graphical abstract A universal strategy was developed to accurately locate the nuclear region and obtain precise molecular information of cell nuclei by SERS.

TensorFlow: Large-Scale Machine Learning on Heterogeneous Distributed Systems

OpenAIRE

Abadi, Martín; Agarwal, Ashish; Barham, Paul; Brevdo, Eugene; Chen, Zhifeng; Citro, Craig; Corrado, Greg S.; Davis, Andy; Dean, Jeffrey; Devin, Matthieu; Ghemawat, Sanjay; Goodfellow, Ian; Harp, Andrew; Irving, Geoffrey; Isard, Michael

2016-01-01

TensorFlow is an interface for expressing machine learning algorithms, and an implementation for executing such algorithms. A computation expressed using TensorFlow can be executed with little or no change on a wide variety of heterogeneous systems, ranging from mobile devices such as phones and tablets up to large-scale distributed systems of hundreds of machines and thousands of computational devices such as GPU cards. The system is flexible and can be used to express a wide variety of algo...

Sensemaking in a Value Based Context for Large Scale Complex Engineered Systems

Science.gov (United States)

Sikkandar Basha, Nazareen

The design and the development of Large-Scale Complex Engineered Systems (LSCES) requires the involvement of multiple teams and numerous levels of the organization and interactions with large numbers of people and interdisciplinary departments. Traditionally, requirements-driven Systems Engineering (SE) is used in the design and development of these LSCES. The requirements are used to capture the preferences of the stakeholder for the LSCES. Due to the complexity of the system, multiple levels of interactions are required to elicit the requirements of the system within the organization. Since LSCES involves people and interactions between the teams and interdisciplinary departments, it should be socio-technical in nature. The elicitation of the requirements of most large-scale system projects are subjected to creep in time and cost due to the uncertainty and ambiguity of requirements during the design and development. In an organization structure, the cost and time overrun can occur at any level and iterate back and forth thus increasing the cost and time. To avoid such creep past researches have shown that rigorous approaches such as value based designing can be used to control it. But before the rigorous approaches can be used, the decision maker should have a proper understanding of requirements creep and the state of the system when the creep occurs. Sensemaking is used to understand the state of system when the creep occurs and provide a guidance to decision maker. This research proposes the use of the Cynefin framework, sensemaking framework which can be used in the design and development of LSCES. It can aide in understanding the system and decision making to minimize the value gap due to requirements creep by eliminating ambiguity which occurs during design and development. A sample hierarchical organization is used to demonstrate the state of the system at the occurrence of requirements creep in terms of cost and time using the Cynefin framework. These

Participatory Design and the Challenges of Large-Scale Systems

DEFF Research Database (Denmark)

Simonsen, Jesper; Hertzum, Morten

2008-01-01

With its 10th biannual anniversary conference, Participatory Design (PD) is leaving its teens and must now be considered ready to join the adult world. In this article we encourage the PD community to think big: PD should engage in large-scale information-systems development and opt for a PD...

A Simple Instrumentation System for Large Structure Vibration Monitoring

Directory of Open Access Journals (Sweden)

Didik R. Santoso

2010-12-01

Full Text Available Traditional instrumentation systems used for monitoring vibration of large-scale infrastructure building such as bridges, railway, and others structural building, generally have a complex design. Makes it simple would be very useful both in terms of low-cost and easy maintenance. This paper describes how to develop the instrumentation system. The system is built based on distributed network, with field bus topology, using single-master multi-slave architecture. Master is a control unit, built based on a PC equipped with RS-485 interface. Slave is a sensing unit; each slave was built by integrating a 3-axis vibration sensor with a microcontroller based data acquisition system. Vibration sensor is designed using the main components of a MEMS accelerometer. While the software is developed for two functions: as a control system hardware and data processing. To verify performance of the developed instrumentation system, several laboratory tests have been performed. The result shows that the system has good performance.

An improved safeguards system and its application to large backend facilities

International Nuclear Information System (INIS)

1978-12-01

The evaluation criteria, which are commonly applicable to both Material Accountancy (MA) and Containment and Surveillance (C/S) and applicable to a large backend facilities, are discussed. It is analyzed that substantial increase of the proliferation resistance can be expected by improving the presently existing safeguards systems. The improved safeguards system described in this paper is expected to be applicable to large-scaled backend facilities without giving unnecessary economical and technical burdens. The main purpose of this approach is to move away from the present trend of too much reliance on MA and to develop the synthetical safeguards effects by harmonizing C/S and continuing MA effectively

Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

Science.gov (United States)

Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

2018-02-01

We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

Senior Management Use of Management Control Systems in Large Companies

DEFF Research Database (Denmark)

Willert, Jeanette; Israelsen, Poul; Rohde, Carsten

2017-01-01

The use of management control systems in large companies remains relatively unexplored. Indeed, only a few studies of senior managers’ use of management control systems consider multiple controls in companies. This paper explores data from a comprehensive survey of the use of management control...... systems in 120 strategic business units at some of the largest companies in Denmark. The paper identifies how senior management guides and controls their subordinates to meet their companies’ objectives. The presentation and discussion of the results, including citations from executive managers, use...

Defining Execution Viewpoints for a Large and Complex Software-Intensive System

NARCIS (Netherlands)

Callo Arias, Trosky B.; America, Pierre; Avgeriou, Paris

2009-01-01

An execution view is an important asset for developing large and complex systems. An execution view helps practitioners to describe, analyze, and communicate what a software system does at runtime and how it does it. In this paper, we present an approach to define execution viewpoints for an

Recommendations for the design and the installation of large laser scanning microscopy systems

Science.gov (United States)

Helm, P. Johannes

2012-03-01

Laser Scanning Microscopy (LSM) has since the inventions of the Confocal Scanning Laser Microscope (CLSM) and the Multi Photon Laser Scanning Microscope (MPLSM) developed into an essential tool in contemporary life science and material science. The market provides an increasing number of turn-key and hands-off commercial LSM systems, un-problematic to purchase, set up and integrate even into minor research groups. However, the successful definition, financing, acquisition, installation and effective use of one or more large laser scanning microscopy systems, possibly of core facility character, often requires major efforts by senior staff members of large academic or industrial units. Here, a set of recommendations is presented, which are helpful during the process of establishing large systems for confocal or non-linear laser scanning microscopy as an effective operational resource in the scientific or industrial production process. Besides the description of technical difficulties and possible pitfalls, the article also illuminates some seemingly "less scientific" processes, i.e. the definition of specific laboratory demands, advertisement of the intention to purchase one or more large systems, evaluation of quotations, establishment of contracts and preparation of the local environment and laboratory infrastructure.

Enzymatic logic calculation systems based on solid-state electrochemiluminescence and molecularly imprinted polymer film electrodes.

Science.gov (United States)

Lian, Wenjing; Liang, Jiying; Shen, Li; Jin, Yue; Liu, Hongyun

2018-02-15

The molecularly imprinted polymer (MIP) films were electropolymerized on the surface of Au electrodes with luminol and pyrrole (PY) as the two monomers and ampicillin (AM) as the template molecule. The electrochemiluminescence (ECL) intensity peak of polyluminol (PL) of the AM-free MIP films at 0.7V vs Ag/AgCl could be greatly enhanced by AM rebinding. In addition, the ECL signals of the MIP films could also be enhanced by the addition of glucose oxidase (GOD)/glucose and/or ferrocenedicarboxylic acid (Fc(COOH) 2 ) in the testing solution. Moreover, Fc(COOH) 2 exhibited cyclic voltammetric (CV) response at the AM-free MIP film electrodes. Based on these results, a binary 3-input/6-output biomolecular logic gate system was established with AM, GOD and Fc(COOH) 2 as inputs and the ECL responses at different levels and CV signal as outputs. Some functional non-Boolean logic devices such as an encoder, a decoder and a demultiplexer were also constructed on the same platform. Particularly, on the basis of the same system, a ternary AND logic gate was established. The present work combined MIP film electrodes, the solid-state ECL, and the enzymatic reaction together, and various types of biomolecular logic circuits and devices were developed, which opened a novel avenue to construct more complicated bio-logic gate systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Thermal System Analysis and Optimization of Large-Scale Compressed Air Energy Storage (CAES

Directory of Open Access Journals (Sweden)

Zhongguang Fu

2015-08-01

Full Text Available As an important solution to issues regarding peak load and renewable energy resources on grids, large-scale compressed air energy storage (CAES power generation technology has recently become a popular research topic in the area of large-scale industrial energy storage. At present, the combination of high-expansion ratio turbines with advanced gas turbine technology is an important breakthrough in energy storage technology. In this study, a new gas turbine power generation system is coupled with current CAES technology. Moreover, a thermodynamic cycle system is optimized by calculating for the parameters of a thermodynamic system. Results show that the thermal efficiency of the new system increases by at least 5% over that of the existing system.

Representative elements: A step to large-scale fracture system simulation

International Nuclear Information System (INIS)

Clemo, T.M.

1987-01-01

Large-scale simulation of flow and transport in fractured media requires the development of a technique to represent the effect of a large number of fractures. Representative elements are used as a tool to model a subset of a fracture system as a single distributed entity. Representative elements are part of a modeling concept called dual permeability. Dual permeability modeling combines discrete fracture simulation of the most important fractures with the distributed modeling of the less important fracture of a fracture system. This study investigates the use of stochastic analysis to determine properties of representative elements. Given an assumption of fully developed laminar flow, the net fracture conductivities and hence flow velocities can be determined from descriptive statistics of fracture spacing, orientation, aperture, and extent. The distribution of physical characteristics about their mean leads to a distribution of the associated conductivities. The variance of hydraulic conductivity induces dispersion into the transport process. Simple fracture systems are treated to demonstrate the usefulness of stochastic analysis. Explicit equations for conductivity of an element are developed and the dispersion characteristics are shown. Explicit formulation of the hydraulic conductivity and transport dispersion reveals the dependence of these important characteristics on the parameters used to describe the fracture system. Understanding these dependencies will help to focus efforts to identify the characteristics of fracture systems. Simulations of stochastically generated fracture sets do not provide this explicit functional dependence on the fracture system parameters. 12 refs., 6 figs

Backup flexibility classes in emerging large-scale renewable electricity systems

International Nuclear Information System (INIS)

Schlachtberger, D.P.; Becker, S.; Schramm, S.; Greiner, M.

2016-01-01

Highlights: • Flexible backup demand in a European wind and solar based power system is modelled. • Three flexibility classes are defined based on production and consumption timescales. • Seasonal backup capacities are shown to be only used below 50% renewable penetration. • Large-scale transmission between countries can reduce fast flexible capacities. - Abstract: High shares of intermittent renewable power generation in a European electricity system will require flexible backup power generation on the dominant diurnal, synoptic, and seasonal weather timescales. The same three timescales are already covered by today’s dispatchable electricity generation facilities, which are able to follow the typical load variations on the intra-day, intra-week, and seasonal timescales. This work aims to quantify the changing demand for those three backup flexibility classes in emerging large-scale electricity systems, as they transform from low to high shares of variable renewable power generation. A weather-driven modelling is used, which aggregates eight years of wind and solar power generation data as well as load data over Germany and Europe, and splits the backup system required to cover the residual load into three flexibility classes distinguished by their respective maximum rates of change of power output. This modelling shows that the slowly flexible backup system is dominant at low renewable shares, but its optimized capacity decreases and drops close to zero once the average renewable power generation exceeds 50% of the mean load. The medium flexible backup capacities increase for modest renewable shares, peak at around a 40% renewable share, and then continuously decrease to almost zero once the average renewable power generation becomes larger than 100% of the mean load. The dispatch capacity of the highly flexible backup system becomes dominant for renewable shares beyond 50%, and reach their maximum around a 70% renewable share. For renewable shares

Simplified DFT methods for consistent structures and energies of large systems

Science.gov (United States)

Caldeweyher, Eike; Gerit Brandenburg, Jan

2018-05-01

Kohn–Sham density functional theory (DFT) is routinely used for the fast electronic structure computation of large systems and will most likely continue to be the method of choice for the generation of reliable geometries in the foreseeable future. Here, we present a hierarchy of simplified DFT methods designed for consistent structures and non-covalent interactions of large systems with particular focus on molecular crystals. The covered methods are a minimal basis set Hartree–Fock (HF-3c), a small basis set screened exchange hybrid functional (HSE-3c), and a generalized gradient approximated functional evaluated in a medium-sized basis set (B97-3c), all augmented with semi-classical correction potentials. We give an overview on the methods design, a comprehensive evaluation on established benchmark sets for geometries and lattice energies of molecular crystals, and highlight some realistic applications on large organic crystals with several hundreds of atoms in the primitive unit cell.

On line surveillance of large systems: applications to nuclear and chemical plant

International Nuclear Information System (INIS)

Zwingelstein, G.

1978-01-01

An on line surveillance method for large scale and distributed parameter systems is achieved by comparing in real time the internal physical parameter values to the reference values. It is shown that the following steps are necessary: modeling, model validation using dynamic testing and on line estimation of parameters. For large scale systems where only few outputs are measurable, an estimation algorithm was developed, selecting the measurable output giving the minimum variance of the physical parameters. This estimation scheme uses a quasilinearization technique associated to the sensitivity equation and the recursive least squares techniques. For large scale systems of order greater than 100, two versions of the estimation scheme are proposed to decrease the computation time. An application to a nuclear reactor core (state variable model of order 29) is proposed and used real data. For distributed systems the estimation scheme was developed with either measurements at fixed time or at fixed space. The estimation algorithm selects the set of measurements that gives the minimum variance of the estimates. An application to a liquid-liquid extraction column, modelized by a set of four coupled partial differential equations, demonstrates the efficiency of the method

Perspectives of biomolecular NMR in drug discovery: the blessing and curse of versatility

International Nuclear Information System (INIS)

Jahnke, Wolfgang

2007-01-01

The versatility of NMR and its broad applicability to several stages in the drug discovery process is well known and generally considered one of the major strengths of NMR (Pellecchia et al., Nature Rev Drug Discov 1:211-219, 2002; Stockman and Dalvit, Prog Nucl Magn Reson Spectrosc 41:187-231, 2002; Lepre et al., Comb Chem High throughput screen 5:583-590, 2002; Wyss et al., Curr Opin Drug Discov Devel 5:630-647, 2002; Jahnke and Widmer, Cell Mol Life Sci 61:580-599, 2004; Huth et al., Methods Enzymol 394:549-571, 2005b; Klages et al., Mol Biosyst 2:318-332, 2006; Takeuchi and Wagner, Curr Opin Struct Biol 16:109-117, 2006; Zartler and Shapiro, Curr Pharm Des 12:3963-3972, 2006). Indeed, NMR is the only biophysical technique which can detect and quantify molecular interactions, and at the same time provide detailed structural information with atomic level resolution. NMR should therefore be ideally suited and widely requested as a tool for drug discovery research, and numerous examples of drug discovery projects which have substantially benefited from NMR contributions or were even driven by NMR have been described in the literature. However, not all pharmaceutical companies have rigorously implemented NMR as integral tool of their research processes. Some companies invest with limited resources, and others do not use biomolecular NMR at all. This discrepancy in assessing the value of a technology is striking, and calls for clarification-under which circumstances can NMR provide added value to the drug discovery process? What kind of contributions can NMR make, and how is it implemented and integrated for maximum impact? This perspectives article suggests key areas of impact for NMR, and a model of integrating NMR with other technologies to realize synergies and maximize their value for drug discovery

Classification of Modern and Old Río Tinto Sedimentary Deposits Through the Biomolecular Record Using a Life Marker Biochip: Implications for Detecting Life on Mars

Science.gov (United States)

Parro, Victor; Fernández-Remolar, David; Rodríguez-Manfredi, José A.; Cruz-Gil, Patricia; Rivas, Luis A.; Ruiz-Bermejo, Marta; Moreno-Paz, Mercedes; García-Villadangos, Miriam; Gómez-Ortiz, David; Blanco-López, Yolanda; Menor-Salván, César; Prieto-Ballesteros, Olga; Gómez-Elvira, Javier

2011-01-01

The particular mineralogy formed in the acidic conditions of the Río Tinto has proven to be a first-order analogue for the acid-sulfate aqueous environments of Mars. Therefore, studies about the formation and preservation of biosignatures in the Río Tinto will provide insights into equivalent processes on Mars. We characterized the biomolecular patterns recorded in samples of modern and old fluvial sediments along a segment of the river by means of an antibody microarray containing more than 200 antibodies (LDCHIP200, for Life Detector Chip) against whole microorganisms, universal biomolecules, or environmental extracts. Samples containing 0.3-0.5g of solid material were automatically analyzed in situ by the Signs Of LIfe Detector instrument (SOLID2), and the results were corroborated by extensive analysis in the laboratory. Positive antigen-antibody reactions indicated the presence of microbial strains or high-molecular-weight biopolymers that originated from them. The LDCHIP200 results were quantified and subjected to a multivariate analysis for immunoprofiling. We associated similar immunopatterns, and biomolecular markers, to samples with similar sedimentary age. Phyllosilicate-rich samples from modern fluvial sediments gave strong positive reactions with antibodies against bacteria of the genus Acidithiobacillus and against biochemical extracts from Río Tinto sediments and biofilms. These samples contained high amounts of sugars (mostly polysaccharides) with monosaccharides like glucose, rhamnose, fucose, and so on. By contrast, the older deposits, which are a mix of clastic sands and evaporites, showed only a few positives with LDCHIP200, consistent with lower protein and sugar content. We conclude that LDCHIP200 results can establish a correlation between microenvironments, diagenetic stages, and age with the biomarker profile associated with a sample. Our results would help in the search for putative martian biomarkers in acidic deposits with similar

Classification of modern and old Río Tinto sedimentary deposits through the biomolecular record using a life marker biochip: implications for detecting life on Mars.

Science.gov (United States)

Parro, Victor; Fernández-Remolar, David; Rodríguez-Manfredi, José A; Cruz-Gil, Patricia; Rivas, Luis A; Ruiz-Bermejo, Marta; Moreno-Paz, Mercedes; García-Villadangos, Miriam; Gómez-Ortiz, David; Blanco-López, Yolanda; Menor-Salván, César; Prieto-Ballesteros, Olga; Gómez-Elvira, Javier

2011-01-01

The particular mineralogy formed in the acidic conditions of the Río Tinto has proven to be a first-order analogue for the acid-sulfate aqueous environments of Mars. Therefore, studies about the formation and preservation of biosignatures in the Río Tinto will provide insights into equivalent processes on Mars. We characterized the biomolecular patterns recorded in samples of modern and old fluvial sediments along a segment of the river by means of an antibody microarray containing more than 200 antibodies (LDCHIP200, for Life Detector Chip) against whole microorganisms, universal biomolecules, or environmental extracts. Samples containing 0.3-0.5 g of solid material were automatically analyzed in situ by the Signs Of LIfe Detector instrument (SOLID2), and the results were corroborated by extensive analysis in the laboratory. Positive antigen-antibody reactions indicated the presence of microbial strains or high-molecular-weight biopolymers that originated from them. The LDCHIP200 results were quantified and subjected to a multivariate analysis for immunoprofiling. We associated similar immunopatterns, and biomolecular markers, to samples with similar sedimentary age. Phyllosilicate-rich samples from modern fluvial sediments gave strong positive reactions with antibodies against bacteria of the genus Acidithiobacillus and against biochemical extracts from Río Tinto sediments and biofilms. These samples contained high amounts of sugars (mostly polysaccharides) with monosaccharides like glucose, rhamnose, fucose, and so on. By contrast, the older deposits, which are a mix of clastic sands and evaporites, showed only a few positives with LDCHIP200, consistent with lower protein and sugar content. We conclude that LDCHIP200 results can establish a correlation between microenvironments, diagenetic stages, and age with the biomarker profile associated with a sample. Our results would help in the search for putative martian biomarkers in acidic deposits with similar

Diffusion of a protein in configuration space

Energy Technology Data Exchange (ETDEWEB)

Garcia, A.E.; Blumenfeld, R.; Hummer, G.; Sobehart, J.

1995-09-01

Simulations of biomolecular dynamics are commonly interpreted in terms of harmonic or quasi-harmonic models for the dynamics of the system. These models assume that biomolecules exhibit oscillations around a single energy minimum. However, spectroscopic data on myoglobin suggest that proteins sample multiple minima. Transitions between minima reveal a broad distribution of energy barriers. This behavior has been observed in other biomolecular systems. To elucidate the nature of protein dynamics the authors have studied a 1.2ns molecular dynamics trajectory of crambin in aqueous solution. This trajectory samples multiple local energy minima. Transitions between minima involve collective motions of amino acids over long distances. The authors show that nonlinear motions are responsible for most of the atomic fluctuations of the protein. These atomic fluctuations are not well described by large motions of individual atoms or a small group of atoms, but rather by concerted motions of many atoms. These nonlinear motions describe transitions between different basins of attraction. The signature of these motions manifests in local and global structural variables. A method for extracting Molecule Optimal Dynamic Coordinates (MODC) is presented.

The key network communication technology in large radiation image cooperative process system

International Nuclear Information System (INIS)

Li Zheng; Kang Kejun; Gao Wenhuan; Wang Jingjin

1998-01-01

Large container inspection system (LCIS) based on radiation imaging technology is a powerful tool for the customs to check the contents inside a large container without opening it. An image distributed network system is composed of operation manager station, image acquisition station, environment control station, inspection processing station, check-in station, check-out station, database station by using advanced network technology. Mass data, such as container image data, container general information, manifest scanning data, commands and status, must be on-line transferred between different stations. Advanced network communication technology is presented

Application and study of advanced network technology in large container inspection system

International Nuclear Information System (INIS)

Li Zheng; Kang Kejun; Gao Wenhuan; Wang Jingjin

1996-01-01

Large Container Inspection System (LCIS) based on radiation imaging technology is a powerful tool for the customs to check the contents inside a large container without opening it. An image distributed network system is composed of center manager station, image acquisition station, environment control station, inspection processing station, check-in station, check-out station, database station by using advanced network technology. Mass data, such as container image data, container general information, manifest scanning data, commands and status, must be on-line transferred between different stations. Advanced network technology and software programming technique are presented

Robust stability analysis of large power systems using the structured singular value theory

Energy Technology Data Exchange (ETDEWEB)

Castellanos, R.; Sarmiento, H. [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico); Messina, A.R. [Cinvestav, Graduate Program in Electrical Engineering, Guadalajara, Jalisco (Mexico)

2005-07-01

This paper examines the application of structured singular value (SSV) theory to analyse robust stability of complex power systems with respect to a set of structured uncertainties. Based on SSV theory and the frequency sweep method, techniques for robust analysis of large-scale power systems are developed. The main interest is focused on determining robust stability for varying operating conditions and uncertainties in the structure of the power system. The applicability of the proposed techniques is verified through simulation studies on a large-scale power system. In particular, results for the system are considered for a wide range of uncertainties of operating conditions. Specifically, the developed technique is used to estimate the effect of variations in the parameters of a major system inter-tie on the nominal stability of a critical inter-area mode. (Author)

Advanced energy systems (APU) for large commercial aircraft

Energy Technology Data Exchange (ETDEWEB)

Westenberger, A.; Bleil, J.; Arendt, M. [Airbus Deutschland GmbH, Hamburg (Germany)

2013-06-01

The intention of using a highly integrated component using on fuel cell technology installed on board of large commercial passenger aircraft for the generation of onboard power for the systems demand during an entire aircraft mission was subject of several studies. The results of these studies have been based on the simulation of the whole system in the context of an aircraft system environment. In front of the work stood the analyses of different fuel cell technologies and the analyses of the aircraft system environment. Today onboard power is provided on ground by an APU and in flight by the main engines. In order to compare fuel cell technology with the today's usual gas turbine operational characteristics have been analysed. A second analysis was devoted to the system demand for typical aircraft categories. The MEA system concept was supposed in all cases. The favourable concept represented an aircraft propelled by conventional engines with starter generator units, providing AC electrical power, covering in total proximately half of the power demand and a component based on fuel cell technology. This component provided electrical DC power, clean potable water, thermal energy at 180 degrees Celsius and nitrogen enriched air for fire suppression and fire extinguishing agent. In opposite of a usual gas turbine based APU, this new unit was operated as the primary power system. (orig.)

Algorithms for large scale singular value analysis of spatially variant tomography systems

International Nuclear Information System (INIS)

Cao-Huu, Tuan; Brownell, G.; Lachiver, G.

1996-01-01

The problem of determining the eigenvalues of large matrices occurs often in the design and analysis of modem tomography systems. As there is an interest in solving systems containing an ever-increasing number of variables, current research effort is being made to create more robust solvers which do not depend on some special feature of the matrix for convergence (e.g. block circulant), and to improve the speed of already known and understood solvers so that solving even larger systems in a reasonable time becomes viable. Our standard techniques for singular value analysis are based on sparse matrix factorization and are not applicable when the input matrices are large because the algorithms cause too much fill. Fill refers to the increase of non-zero elements in the LU decomposition of the original matrix A (the system matrix). So we have developed iterative solutions that are based on sparse direct methods. Data motion and preconditioning techniques are critical for performance. This conference paper describes our algorithmic approaches for large scale singular value analysis of spatially variant imaging systems, and in particular of PCR2, a cylindrical three-dimensional PET imager 2 built at the Massachusetts General Hospital (MGH) in Boston. We recommend the desirable features and challenges for the next generation of parallel machines for optimal performance of our solver

Computer code package RALLY for probabilistic safety assessment of large technical systems

International Nuclear Information System (INIS)

Gueldner, W.; Polke, H.; Spindler, H.; Zipf, G.

1981-09-01

This report describes the program system RALLY to compute the reliability of large and intermeshed technical systems. In addition to a short explanation of the different programs, the possible applications of the program system RALLY are demonstrated. Finally, the most important studies carried out so far on RALLY are discussed. (orig.) [de

Energy System Analysis of Large-Scale Integration of Wind Power

International Nuclear Information System (INIS)

Lund, Henrik

2003-11-01

The paper presents the results of two research projects conducted by Aalborg University and financed by the Danish Energy Research Programme. Both projects include the development of models and system analysis with focus on large-scale integration of wind power into different energy systems. Market reactions and ability to exploit exchange on the international market for electricity by locating exports in hours of high prices are included in the analyses. This paper focuses on results which are valid for energy systems in general. The paper presents the ability of different energy systems and regulation strategies to integrate wind power, The ability is expressed by three factors: One factor is the degree of electricity excess production caused by fluctuations in wind and CHP heat demands. The other factor is the ability to utilise wind power to reduce CO 2 emission in the system. And the third factor is the ability to benefit from exchange of electricity on the market. Energy systems and regulation strategies are analysed in the range of a wind power input from 0 to 100% of the electricity demand. Based on the Danish energy system, in which 50 per cent of the electricity demand is produced in CHP, a number of future energy systems with CO 2 reduction potentials are analysed, i.e. systems with more CHP, systems using electricity for transportation (battery or hydrogen vehicles) and systems with fuel-cell technologies. For the present and such potential future energy systems different regulation strategies have been analysed, i.e. the inclusion of small CHP plants into the regulation task of electricity balancing and grid stability and investments in electric heating, heat pumps and heat storage capacity. Also the potential of energy management has been analysed. The results of the analyses make it possible to compare short-term and long-term potentials of different strategies of large-scale integration of wind power

Large resistivity modulation in mixed-phase metallic systems.

Science.gov (United States)

Lee, Yeonbae; Liu, Z Q; Heron, J T; Clarkson, J D; Hong, J; Ko, C; Biegalski, M D; Aschauer, U; Hsu, S L; Nowakowski, M E; Wu, J; Christen, H M; Salahuddin, S; Bokor, J B; Spaldin, N A; Schlom, D G; Ramesh, R

2015-01-07

In numerous systems, giant physical responses have been discovered when two phases coexist; for example, near a phase transition. An intermetallic FeRh system undergoes a first-order antiferromagnetic to ferromagnetic transition above room temperature and shows two-phase coexistence near the transition. Here we have investigated the effect of an electric field to FeRh/PMN-PT heterostructures and report 8% change in the electrical resistivity of FeRh films. Such a 'giant' electroresistance (GER) response is striking in metallic systems, in which external electric fields are screened, and thus only weakly influence the carrier concentrations and mobilities. We show that our FeRh films comprise coexisting ferromagnetic and antiferromagnetic phases with different resistivities and the origin of the GER effect is the strain-mediated change in their relative proportions. The observed behaviour is reminiscent of colossal magnetoresistance in perovskite manganites and illustrates the role of mixed-phase coexistence in achieving large changes in physical properties with low-energy external perturbation.

Iterative solution of large sparse systems of equations

CERN Document Server

Hackbusch, Wolfgang

2016-01-01

In the second edition of this classic monograph, complete with four new chapters and updated references, readers will now have access to content describing and analysing classical and modern methods with emphasis on the algebraic structure of linear iteration, which is usually ignored in other literature. The necessary amount of work increases dramatically with the size of systems, so one has to search for algorithms that most efficiently and accurately solve systems of, e.g., several million equations. The choice of algorithms depends on the special properties the matrices in practice have. An important class of large systems arises from the discretization of partial differential equations. In this case, the matrices are sparse (i.e., they contain mostly zeroes) and well-suited to iterative algorithms. The first edition of this book grew out of a series of lectures given by the author at the Christian-Albrecht University of Kiel to students of mathematics. The second edition includes quite novel approaches.

Quarkonia production in small and large systems measured by ATLAS

CERN Document Server

Lopez, Jorge; The ATLAS collaboration

2018-01-01

The experimentally observed dissociation and regeneration of bound quarkonium states in heavy-ion collisions provide a powerful tool to probe the dynamics of the hot, dense plasma. These measurements are sensitive to the effects of color screening, color recombination, or other, new suppression mechanisms. In the large-statistics Run 2 lead-lead and proton-lead collision data, these phenomena can be probed with unprecedented precision. Measurements of the ground and excited quarkonia states, as well as their separation into prompt and non-prompt components, provide further opportunities to study the dynamics of heavy parton energy loss in these large systems. In addition, quarkonium production rates, and their excited to ground states ratios, in small, asymmetric systems are an interesting probe of cold nuclear matter effects. In this talk, the latest ATLAS results on quarkonia production will be presented, including new, differential measurements of charmonium suppression and azimuthal modulation in lead-lea...

Challenges for Super-Resolution Localization Microscopy and Biomolecular Fluorescent Nano-Probing in Cancer Research

Science.gov (United States)

Ilić, Nataša; Pilarczyk, Götz; Lee, Jin-Ho; Logeswaran, Abiramy; Borroni, Aurora Paola; Krufczik, Matthias; Theda, Franziska; Waltrich, Nadine; Bestvater, Felix; Hildenbrand, Georg; Cremer, Christoph; Blank, Michael

2017-01-01

Understanding molecular interactions and regulatory mechanisms in tumor initiation, progression, and treatment response are key requirements towards advanced cancer diagnosis and novel treatment procedures in personalized medicine. Beyond decoding the gene expression, malfunctioning and cancer-related epigenetic pathways, investigations of the spatial receptor arrangements in membranes and genome organization in cell nuclei, on the nano-scale, contribute to elucidating complex molecular mechanisms in cells and tissues. By these means, the correlation between cell function and spatial organization of molecules or molecular complexes can be studied, with respect to carcinogenesis, tumor sensitivity or tumor resistance to anticancer therapies, like radiation or antibody treatment. Here, we present several new applications for bio-molecular nano-probes and super-resolution, laser fluorescence localization microscopy and their potential in life sciences, especially in biomedical and cancer research. By means of a tool-box of fluorescent antibodies, green fluorescent protein (GFP) tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors in membranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2) in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by radiation or antibody treatment. The main purpose of this article is to demonstrate how nano-scaled distance measurements between bio-molecules, tagged by appropriate nano-probes, can be applied to elucidate structures and conformations of molecular complexes which are characteristic of tumorigenesis and treatment responses. These applications open new avenues towards a better interpretation of the spatial organization and treatment responses of functionally relevant molecules, at the single cell level, in normal and cancer cells, offering new potentials for individualized medicine. PMID:28956810

Challenges for Super-Resolution Localization Microscopy and Biomolecular Fluorescent Nano-Probing in Cancer Research

Directory of Open Access Journals (Sweden)

Michael Hausmann

2017-09-01

Full Text Available Understanding molecular interactions and regulatory mechanisms in tumor initiation, progression, and treatment response are key requirements towards advanced cancer diagnosis and novel treatment procedures in personalized medicine. Beyond decoding the gene expression, malfunctioning and cancer-related epigenetic pathways, investigations of the spatial receptor arrangements in membranes and genome organization in cell nuclei, on the nano-scale, contribute to elucidating complex molecular mechanisms in cells and tissues. By these means, the correlation between cell function and spatial organization of molecules or molecular complexes can be studied, with respect to carcinogenesis, tumor sensitivity or tumor resistance to anticancer therapies, like radiation or antibody treatment. Here, we present several new applications for bio-molecular nano-probes and super-resolution, laser fluorescence localization microscopy and their potential in life sciences, especially in biomedical and cancer research. By means of a tool-box of fluorescent antibodies, green fluorescent protein (GFP tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors in membranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2 in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by radiation or antibody treatment. The main purpose of this article is to demonstrate how nano-scaled distance measurements between bio-molecules, tagged by appropriate nano-probes, can be applied to elucidate structures and conformations of molecular complexes which are characteristic of tumorigenesis and treatment responses. These applications open new avenues towards a better interpretation of the spatial organization and treatment responses of functionally relevant molecules, at the single cell level, in normal and cancer cells, offering new potentials for individualized medicine.

The linac control system for the large-scale synchrotron radiation facility (SPring-8)

Energy Technology Data Exchange (ETDEWEB)

Sakaki, Hironao; Yoshikawa, Hiroshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Itoh, Yuichi [Atomic Energy General Services Corporation, Tokai, Ibaraki (Japan); Terashima, Yasushi [Information Technology System Co., Ltd. (ITECS), Tokyo (Japan)

2000-09-01

The linac for large-scale synchrotron radiation facilities has been operated since August of 1996. The linac deal with the user requests without any big troubles. In this report, the control system development policy, details, and the operation for the linac are presented. It is also described so that these experiences can be used for control system of a large scale proton accelerators which will be developed in the High Intensity Proton Accelerator Project. (author)

Radiofrequency and microwave interactions between biomolecular systems

Czech Academy of Sciences Publication Activity Database

Kučera, Ondřej; Cifra, Michal

2016-01-01

Roč. 42, č. 1 (2016), s. 1-8 ISSN 0092-0606 R&D Projects: GA ČR(CZ) GA15-17102S Institutional support: RVO:67985882 Keywords : Cell signaling * Radiofrequency * Bioelectrodynamics Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.241, year: 2016

Hierarchical, decentralized control system for large-scale smart-structures

International Nuclear Information System (INIS)

Algermissen, Stephan; Fröhlich, Tim; Monner, Hans Peter

2014-01-01

Active control of sound and vibration has gained much attention in all kinds of industries in the past decade. Future prospects for maximizing airline passenger comfort are especially promising. The objectives of recent research projects in this area are the reduction of noise transmission through thin walled structures such as fuselages, linings or interior elements. Besides different external noise sources, such as the turbulent boundary layer, rotor or jet noise, the actuator and sensor placement as well as different control concepts are addressed. Mostly, the work is focused on a single panel or section of the fuselage, neglecting the fact that for effective noise reduction the entire fuselage has to be taken into account. Nevertheless, extending the scope of an active system from a single panel to the entire fuselage increases the effort for control hardware dramatically. This paper presents a control concept for large structures using distributed control nodes. Each node has the capability to execute a vibration or noise controller for a specific part or section of the fuselage. For maintenance, controller tuning or performance measurement, all nodes are connected to a host computer via Universal Serial Bus (USB). This topology allows a partitioning and distributing of tasks. The nodes execute the low-level control functions. High-level tasks like maintenance, system identification and control synthesis are operated by the host using streamed data from the nodes. By choosing low-price nodes, a very cost effective way of implementing an active system for large structures is realized. Besides the system identification and controller synthesis on the host computer, a detailed view on the hardware and software concept for the nodes is given. Finally, the results of an experimental test of a system running a robust vibration controller at an active panel demonstrator are shown. (paper)

Senior Management Use of Management Control Systems in Large Companies

DEFF Research Database (Denmark)

Willert, Jeanette; Israelsen, Poul; Rohde, Carsten

2017-01-01

Ferreira and Otley’s (2009) conceptual and holistic framework for performance management systems, supplemented by elements of contextual factors and organisational culture. Further, selected researchers’ perceptions of the purpose of using management control systems are related to practitioners’ ideas......The use of management control systems in large companies remains relatively unexplored. Indeed, only a few studies of senior managers’ use of management control systems consider multiple controls in companies. This paper explores data from a comprehensive survey of the use of management control...... systems in 120 strategic business units at some of the largest companies in Denmark. The paper identifies how senior management guides and controls their subordinates to meet their companies’ objectives. The presentation and discussion of the results, including citations from executive managers, use...

Rucio - The next generation large scale distributed system for ATLAS Data Management

CERN Document Server

Beermann, T; The ATLAS collaboration; Lassnig, M; Barisits, M; Vigne, R; Serfon, C; Stewart, G A; Goossens, L; Nairz, A; Molfetas, A

2014-01-01

Rucio is the next-generation Distributed Data Management (DDM) system benefiting from recent advances in cloud and "Big Data" computing to address the ATLAS experiment scaling requirements. Rucio is an evolution of the ATLAS DDM system Don Quijote 2 (DQ2), which has demonstrated very large scale data management capabilities with more than 150 petabytes spread worldwide across 130 sites, and accesses from 1,000 active users. However, DQ2 is reaching its limits in terms of scalability, requiring a large number of support staff to operate and being hard to extend with new technologies. Rucio will deal with these issues by relying on new technologies to ensure system scalability, address new user requirements and employ a new automation framework to reduce operational overheads.

Research of Control Strategy in the Large Electric Cylinder Position Servo System

Directory of Open Access Journals (Sweden)

Yongguang Liu

2015-01-01

Full Text Available An ideal positioning response is very difficult to realize in the large electric cylinder system that is applied in missile launcher because of the presence of many nonlinear factors such as load disturbance, parameter variations, lost motion, and friction. This paper presents a piecewise control strategy based on the optimized positioning principle. The combined application of position interpolation method and modified incremental PID with dead band is proposed and applied into control system. The experimental result confirms that this combined control strategy is not only simple to be applied into high accuracy real-time control system but also significantly improves dynamic response, steady accuracy, and anti-interference performance, which has very important significance to improve the smooth control of the large electric cylinder.

Modular pump limiter systems for large tokamaks

International Nuclear Information System (INIS)

Uckan, T.; Klepper, C.C.; Mioduszewski, P.K.; McGrath, R.T.

1987-09-01

Long-pulse (>10-s) operation of large tokamaks with high-power (>10-MW) heating and extensive external fueling will require correspondingly efficient particle exhaust for density control. A pump limiter can provide the needed exhaust capability by removing a small percentage of the particles, which would otherwise be recycled. Single pump limiter modules have been operated successfully on ISX-B, PDX, TEXTOR, and PLT. An axisymmetric pump limiter is now being installed and will be studied in TEXTOR. A third type of pump limiter is a system that consists of several modules and exhibits performance different from that of a single module. To take advantage of the flexibility of a modular pump limiter system in a high-power, long-pulse device, the power load must be distributed among a number of modules. Because each added module changes the performance of all the others, a set of design criteria must be defined for the overall limiter system. The design parameters for the modules are then determined from the system requirements for particle and power removal. Design criteria and parameters are presented, and the impact on module design of the state of the art in engineering technology is discussed. The relationship between modules are considered from the standpoint of flux coverage and shadowing effects. The results are applied to the Tore Supra tokamak. A preliminary conceptual design for the Tore Supra pump limiter system is discussed, and the design parameters of the limiter modules are presented. 21 refs., 12 figs

Incipient multiple fault diagnosis in real time with applications to large-scale systems

International Nuclear Information System (INIS)

Chung, H.Y.; Bien, Z.; Park, J.H.; Seon, P.H.

1994-01-01

By using a modified signed directed graph (SDG) together with the distributed artificial neutral networks and a knowledge-based system, a method of incipient multi-fault diagnosis is presented for large-scale physical systems with complex pipes and instrumentations such as valves, actuators, sensors, and controllers. The proposed method is designed so as to (1) make a real-time incipient fault diagnosis possible for large-scale systems, (2) perform the fault diagnosis not only in the steady-state case but also in the transient case as well by using a concept of fault propagation time, which is newly adopted in the SDG model, (3) provide with highly reliable diagnosis results and explanation capability of faults diagnosed as in an expert system, and (4) diagnose the pipe damage such as leaking, break, or throttling. This method is applied for diagnosis of a pressurizer in the Kori Nuclear Power Plant (NPP) unit 2 in Korea under a transient condition, and its result is reported to show satisfactory performance of the method for the incipient multi-fault diagnosis of such a large-scale system in a real-time manner

Development of large scale and wind energy conservation system. Operational studies on a large-scale wind energy conservation system; Ogata furyoku hatsuden system no kaihatsu. Ogata furyoku hatsuden system no unten kenkyu

Energy Technology Data Exchange (ETDEWEB)

Takita, M [New Energy and Industrial Technology Development Organization, Tokyo (Japan)

1994-12-01

Described herein are the results of the FY1994 research program for operational studies on a large-scale wind energy conversion system. A total of 8 domestic and foreign cases are studied for wind energy conversion cost, to clarify the causes for higher cost of the Japanese system. The wind power systems studied include Japanese (5 units at Tappi Wind Park, the same type supplied by company M), US (California Wind Farm, 300 units) and UK (Wales Wind Farm, 103 units) systems. The investment costs are 639, 285 and 189 thousand yen/kW for the Japanese, US and UK systems, respectively. It is also revealed that the power plant itself and assembling costs account for a majority (70 to 88%) of the total investment cost. The higher cost of the Japanese system results from a smaller number of units installed, and the power plant cost can be drastically reduced by mass production. Increasing size also reduces cost greatly.

Very Large Distance Education Systems: The Case of China. ZIFF Papiere 94.

Science.gov (United States)

Keegan, Desmond

One answer to the magnitude of the world education crisis is the provision of very large education systems, capable of enrolling 100,000 students or more. The largest distance system is the Dianda or Chinese Radio and Television University (CRTVU) system. Dianda is best described as a network of one central open university that does not enroll…