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

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

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.

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...

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.

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 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.

Aligning Biomolecular Networks Using Modular Graph Kernels

Science.gov (United States)

Towfic, Fadi; Greenlee, M. Heather West; Honavar, Vasant

Comparative analysis of biomolecular networks constructed using measurements from different conditions, tissues, and organisms offer a powerful approach to understanding the structure, function, dynamics, and evolution of complex biological systems. We explore a class of algorithms for aligning large biomolecular networks by breaking down such networks into subgraphs and computing the alignment of the networks based on the alignment of their subgraphs. The resulting subnetworks are compared using graph kernels as scoring functions. We provide implementations of the resulting algorithms as part of BiNA, an open source biomolecular network alignment toolkit. Our experiments using Drosophila melanogaster, Saccharomyces cerevisiae, Mus musculus and Homo sapiens protein-protein interaction networks extracted from the DIP repository of protein-protein interaction data demonstrate that the performance of the proposed algorithms (as measured by % GO term enrichment of subnetworks identified by the alignment) is competitive with some of the state-of-the-art algorithms for pair-wise alignment of large protein-protein interaction networks. Our results also show that the inter-species similarity scores computed based on graph kernels can be used to cluster the species into a species tree that is consistent with the known phylogenetic relationships among the species.

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...

DNA-assisted swarm control in a biomolecular motor system.

Science.gov (United States)

Keya, Jakia Jannat; Suzuki, Ryuhei; Kabir, Arif Md Rashedul; Inoue, Daisuke; Asanuma, Hiroyuki; Sada, Kazuki; Hess, Henry; Kuzuya, Akinori; Kakugo, Akira

2018-01-31

In nature, swarming behavior has evolved repeatedly among motile organisms because it confers a variety of beneficial emergent properties. These include improved information gathering, protection from predators, and resource utilization. Some organisms, e.g., locusts, switch between solitary and swarm behavior in response to external stimuli. Aspects of swarming behavior have been demonstrated for motile supramolecular systems composed of biomolecular motors and cytoskeletal filaments, where cross-linkers induce large scale organization. The capabilities of such supramolecular systems may be further extended if the swarming behavior can be programmed and controlled. Here, we demonstrate that the swarming of DNA-functionalized microtubules (MTs) propelled by surface-adhered kinesin motors can be programmed and reversibly regulated by DNA signals. Emergent swarm behavior, such as translational and circular motion, can be selected by tuning the MT stiffness. Photoresponsive DNA containing azobenzene groups enables switching between solitary and swarm behavior in response to stimulation with visible or ultraviolet light.

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.

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...

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.

Development of an informatics infrastructure for data exchange of biomolecular simulations: Architecture, data models and ontology.

Science.gov (United States)

Thibault, J C; Roe, D R; Eilbeck, K; Cheatham, T E; Facelli, J C

2015-01-01

Biomolecular simulations aim to simulate structure, dynamics, interactions, and energetics of complex biomolecular systems. With the recent advances in hardware, it is now possible to use more complex and accurate models, but also reach time scales that are biologically significant. Molecular simulations have become a standard tool for toxicology and pharmacology research, but organizing and sharing data - both within the same organization and among different ones - remains a substantial challenge. In this paper we review our recent work leading to the development of a comprehensive informatics infrastructure to facilitate the organization and exchange of biomolecular simulations data. Our efforts include the design of data models and dictionary tools that allow the standardization of the metadata used to describe the biomedical simulations, the development of a thesaurus and ontology for computational reasoning when searching for biomolecular simulations in distributed environments, and the development of systems based on these models to manage and share the data at a large scale (iBIOMES), and within smaller groups of researchers at laboratory scale (iBIOMES Lite), that take advantage of the standardization of the meta data used to describe biomolecular simulations.

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...

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.

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.

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.

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...

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...

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.

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.

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.

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

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.

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.

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

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 ).

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.

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 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.

Optimal number of coarse-grained sites in different components of large biomolecular complexes.

Science.gov (United States)

Sinitskiy, Anton V; Saunders, Marissa G; Voth, Gregory A

2012-07-26

The computational study of large biomolecular complexes (molecular machines, cytoskeletal filaments, etc.) is a formidable challenge facing computational biophysics and biology. To achieve biologically relevant length and time scales, coarse-grained (CG) models of such complexes usually must be built and employed. One of the important early stages in this approach is to determine an optimal number of CG sites in different constituents of a complex. This work presents a systematic approach to this problem. First, a universal scaling law is derived and numerically corroborated for the intensity of the intrasite (intradomain) thermal fluctuations as a function of the number of CG sites. Second, this result is used for derivation of the criterion for the optimal number of CG sites in different parts of a large multibiomolecule complex. In the zeroth-order approximation, this approach validates the empirical rule of taking one CG site per fixed number of atoms or residues in each biomolecule, previously widely used for smaller systems (e.g., individual biomolecules). The first-order corrections to this rule are derived and numerically checked by the case studies of the Escherichia coli ribosome and Arp2/3 actin filament junction. In different ribosomal proteins, the optimal number of amino acids per CG site is shown to differ by a factor of 3.5, and an even wider spread may exist in other large biomolecular complexes. Therefore, the method proposed in this paper is valuable for the optimal construction of CG models of such complexes.

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.)

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.

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

Selected topics in solution-phase biomolecular NMR spectroscopy

Science.gov (United States)

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.

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)

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

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.

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

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

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

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.

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.

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.

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.

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.

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

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…

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.

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.

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.

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...

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.

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.

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

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.

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.

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

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

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.

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)

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

Biomolecular surface construction by PDE transform.

Science.gov (United States)

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

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

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.

Frequency-scanning MALDI linear ion trap mass spectrometer for large biomolecular ion detection.

Science.gov (United States)

Lu, I-Chung; Lin, Jung Lee; Lai, Szu-Hsueh; Chen, Chung-Hsuan

2011-11-01

This study presents the first report on the development of a matrix-assisted laser desorption ionization (MALDI) linear ion trap mass spectrometer for large biomolecular ion detection by frequency scan. We designed, installed, and tested this radio frequency (RF) scan linear ion trap mass spectrometer and its associated electronics to dramatically extend the mass region to be detected. The RF circuit can be adjusted from 300 to 10 kHz with a set of operation amplifiers. To trap the ions produced by MALDI, a high pressure of helium buffer gas was employed to quench extra kinetic energy of the heavy ions produced by MALDI. The successful detection of the singly charged secretory immunoglobulin A ions indicates that the detectable mass-to-charge ratio (m/z) of this system can reach ~385 000 or beyond.

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.

Directory of Open Access Journals (Sweden)

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)

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

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.

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.

Biomolecular Markers in Cancer of the Tongue

Directory of Open Access Journals (Sweden)

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

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.

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

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

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

Science.gov (United States)

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.

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.

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.

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...

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...

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.

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

Science.gov (United States)

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.

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

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.

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.

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.

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.

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)

Generative probabilistic models extend the scope of inferential structure determination

DEFF Research Database (Denmark)

Olsson, Simon; Boomsma, Wouter; Frellsen, Jes

2011-01-01

demonstrate that the use of generative probabilistic models instead of physical forcefields in the Bayesian formalism is not only conceptually attractive, but also improves precision and efficiency. Our results open new vistas for the use of sophisticated probabilistic models of biomolecular structure......Conventional methods for protein structure determination from NMR data rely on the ad hoc combination of physical forcefields and experimental data, along with heuristic determination of free parameters such as weight of experimental data relative to a physical forcefield. Recently, a theoretically...

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.

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.

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

Science.gov (United States)

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.

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.

Traditional biomolecular structure determination by NMR spectroscopy allows for major errors

NARCIS (Netherlands)

Nabuurs, S.B.; Spronk, C.A.E.M.; Vuister, G.W.; Vriend, G.

2006-01-01

One of the major goals of structural genomics projects is to determine the three-dimensional structure of representative members of as many different fold families as possible. Comparative modeling is expected to fill the remaining gaps by providing structural models of homologs of the

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.

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

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.

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...

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

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.

Review of Transducer Principles for Label-Free Biomolecular Interaction Analysis

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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.

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

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...

Imaging and chemical surface analysis of biomolecular functionalization of monolithically integrated on silicon Mach-Zehnder interferometric immunosensors

International Nuclear Information System (INIS)

Gajos, Katarzyna; Angelopoulou, Michailia; Petrou, Panagiota; Awsiuk, Kamil; Kakabakos, Sotirios; Haasnoot, Willem; Bernasik, Andrzej; Rysz, Jakub; Marzec, Mateusz M.; Misiakos, Konstantinos; Raptis, Ioannis; Budkowski, Andrzej

2016-01-01

Highlights: • Optimization of probe immobilization with robotic spotter printing overlapping spots. • In-situ inspection of microstructured surfaces of biosensors integrated on silicon. • Imaging and chemical analysis of immobilization, surface blocking and immunoreaction. • Insight with molecular discrimination into step-by-step sensor surface modifications. • Optimized biofunctionalization improves sensor sensitivity and response repeatability. - Abstract: Time-of-flight secondary ion mass spectrometry (imaging, micro-analysis) has been employed to evaluate biofunctionalization of the sensing arm areas of Mach-Zehnder interferometers monolithically integrated on silicon chips for the immunochemical (competitive) detection of bovine κ-casein in goat milk. Biosensor surfaces are examined after: modification with (3-aminopropyl)triethoxysilane, application of multiple overlapping spots of κ-casein solutions, blocking with 100-times diluted goat milk, and reaction with monoclonal mouse anti-κ-casein antibodies in blocking solution. The areas spotted with κ-casein solutions of different concentrations are examined and optimum concentration providing homogeneous coverage is determined. Coverage of biosensor surfaces with biomolecules after each of the sequential steps employed in immunodetection is also evaluated with TOF-SIMS, supplemented by Atomic force microscopy and X-ray photoelectron spectroscopy. Uniform molecular distributions are observed on the sensing arm areas after spotting with optimum κ-casein concentration, blocking and immunoreaction. The corresponding biomolecular compositions are determined with a Principal Component Analysis that distinguished between protein amino acids and milk glycerides, as well as between amino acids characteristic for Mabs and κ-casein, respectively. Use of the optimum conditions (κ-casein concentration) for functionalization of chips with arrays of ten Mach-Zehnder interferometers provided on-chips assays

Imaging and chemical surface analysis of biomolecular functionalization of monolithically integrated on silicon Mach-Zehnder interferometric immunosensors

Energy Technology Data Exchange (ETDEWEB)

Gajos, Katarzyna, E-mail: kasia.fornal@uj.edu.pl [M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków (Poland); Angelopoulou, Michailia; Petrou, Panagiota [Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, NCSR Demokritos, P. Grigoriou & Neapoleos St, Aghia Paraksevi 15310, Athens (Greece); Awsiuk, Kamil [M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków (Poland); Kakabakos, Sotirios [Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, NCSR Demokritos, P. Grigoriou & Neapoleos St, Aghia Paraksevi 15310, Athens (Greece); Haasnoot, Willem [RIKILT Wageningen UR, Akkermaalsbos 2, 6708 WB Wageningen (Netherlands); Bernasik, Andrzej [Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Mickiewicza 30, 30-059 Kraków (Poland); Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, Mickiewicza 30, 30-059 Kraków (Poland); Rysz, Jakub [M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków (Poland); Marzec, Mateusz M. [Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, Mickiewicza 30, 30-059 Kraków (Poland); Misiakos, Konstantinos; Raptis, Ioannis [Department of Microelectronics, Institute of Nanoscience and Nanotechnology, NCSR Demokritos, P. Grigoriou & Neapoleos St, Aghia Paraksevi 15310, Athens (Greece); Budkowski, Andrzej [M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków (Poland)

2016-11-01

Highlights: • Optimization of probe immobilization with robotic spotter printing overlapping spots. • In-situ inspection of microstructured surfaces of biosensors integrated on silicon. • Imaging and chemical analysis of immobilization, surface blocking and immunoreaction. • Insight with molecular discrimination into step-by-step sensor surface modifications. • Optimized biofunctionalization improves sensor sensitivity and response repeatability. - Abstract: Time-of-flight secondary ion mass spectrometry (imaging, micro-analysis) has been employed to evaluate biofunctionalization of the sensing arm areas of Mach-Zehnder interferometers monolithically integrated on silicon chips for the immunochemical (competitive) detection of bovine κ-casein in goat milk. Biosensor surfaces are examined after: modification with (3-aminopropyl)triethoxysilane, application of multiple overlapping spots of κ-casein solutions, blocking with 100-times diluted goat milk, and reaction with monoclonal mouse anti-κ-casein antibodies in blocking solution. The areas spotted with κ-casein solutions of different concentrations are examined and optimum concentration providing homogeneous coverage is determined. Coverage of biosensor surfaces with biomolecules after each of the sequential steps employed in immunodetection is also evaluated with TOF-SIMS, supplemented by Atomic force microscopy and X-ray photoelectron spectroscopy. Uniform molecular distributions are observed on the sensing arm areas after spotting with optimum κ-casein concentration, blocking and immunoreaction. The corresponding biomolecular compositions are determined with a Principal Component Analysis that distinguished between protein amino acids and milk glycerides, as well as between amino acids characteristic for Mabs and κ-casein, respectively. Use of the optimum conditions (κ-casein concentration) for functionalization of chips with arrays of ten Mach-Zehnder interferometers provided on-chips assays

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).

Computational Methods for Biomolecular Electrostatics

Science.gov (United States)

Dong, Feng; Olsen, Brett; Baker, Nathan A.

2008-01-01

An understanding of intermolecular interactions is essential for insight into how cells develop, operate, communicate and control their activities. Such interactions include several components: contributions from linear, angular, and torsional forces in covalent bonds, van der Waals forces, as well as electrostatics. Among the various components of molecular interactions, electrostatics are of special importance because of their long range and their influence on polar or charged molecules, including water, aqueous ions, and amino or nucleic acids, which are some of the primary components of living systems. Electrostatics, therefore, play important roles in determining the structure, motion and function of a wide range of biological molecules. This chapter presents a brief overview of electrostatic interactions in cellular systems with a particular focus on how computational tools can be used to investigate these types of interactions. PMID:17964951

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.

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.

Open-ended response theory with polarizable embedding: multiphoton absorption in biomolecular systems.

Science.gov (United States)

Steindal, Arnfinn Hykkerud; Beerepoot, Maarten T P; Ringholm, Magnus; List, Nanna Holmgaard; Ruud, Kenneth; Kongsted, Jacob; Olsen, Jógvan Magnus Haugaard

2016-10-12

We present the theory and implementation of an open-ended framework for electric response properties at the level of Hartree-Fock and Kohn-Sham density functional theory that includes effects from the molecular environment modeled by the polarizable embedding (PE) model. With this new state-of-the-art multiscale functionality, electric response properties to any order can be calculated for molecules embedded in polarizable atomistic molecular environments ranging from solvents to complex heterogeneous macromolecules such as proteins. In addition, environmental effects on multiphoton absorption (MPA) properties can be studied by evaluating single residues of the response functions. The PE approach includes mutual polarization effects between the quantum and classical parts of the system through induced dipoles that are determined self-consistently with respect to the electronic density. The applicability of our approach is demonstrated by calculating MPA strengths up to four-photon absorption for the green fluorescent protein. We show how the size of the quantum region, as well as the treatment of the border between the quantum and classical regions, is crucial in order to obtain reliable MPA predictions.

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.

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

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)

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.

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.

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

Emergency operation determination system

International Nuclear Information System (INIS)

Miki, Tetsushi.

1993-01-01

The system of the present invention can determine an emergency operation coping with abnormal events occurring during nuclear plant operation without replying on an operator's judgement. That is, the system of the present invention comprises an intelligence base which divides and classifies the aims of the plant operation for the function, structure and operation manual and puts them into network. Degree of attainment for the extend of the status normality is determined on every aim of operation based on various kinds of measured data during plant operation. For a degree of attainment within a predetermined range, it is judged that an emergency operation is possible although this is in an abnormal state. Degree of emergency is determined by a fuzzy theory based on the degree of attainment, variation coefficient for the degree of attainment and the sensitivity to external disturbance as parameters. Priority for the degree of emergency on every operation aims is determined by comparison. Normality is successively checked for the determined operation aims. As a result, equipments as objects of abnormality suppressing operation are specified, and the operation amount of the equipments as objects are determined so that the measuring data are within a predetermined range. (I.S.)

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.

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.

Determination of partial molar volumes from free energy perturbation theory†

Science.gov (United States)

Vilseck, Jonah Z.; Tirado-Rives, Julian

2016-01-01

Partial molar volume is an important thermodynamic property that gives insights into molecular size and intermolecular interactions in solution. Theoretical frameworks for determining the partial molar volume (V°) of a solvated molecule generally apply Scaled Particle Theory or Kirkwood–Buff theory. With the current abilities to perform long molecular dynamics and Monte Carlo simulations, more direct methods are gaining popularity, such as computing V° directly as the difference in computed volume from two simulations, one with a solute present and another without. Thermodynamically, V° can also be determined as the pressure derivative of the free energy of solvation in the limit of infinite dilution. Both approaches are considered herein with the use of free energy perturbation (FEP) calculations to compute the necessary free energies of solvation at elevated pressures. Absolute and relative partial molar volumes are computed for benzene and benzene derivatives using the OPLS-AA force field. The mean unsigned error for all molecules is 2.8 cm3 mol−1. The present methodology should find use in many contexts such as the development and testing of force fields for use in computer simulations of organic and biomolecular systems, as a complement to related experimental studies, and to develop a deeper understanding of solute–solvent interactions. PMID:25589343

Determination of partial molar volumes from free energy perturbation theory.

Science.gov (United States)

Vilseck, Jonah Z; Tirado-Rives, Julian; Jorgensen, William L

2015-04-07

Partial molar volume is an important thermodynamic property that gives insights into molecular size and intermolecular interactions in solution. Theoretical frameworks for determining the partial molar volume (V°) of a solvated molecule generally apply Scaled Particle Theory or Kirkwood-Buff theory. With the current abilities to perform long molecular dynamics and Monte Carlo simulations, more direct methods are gaining popularity, such as computing V° directly as the difference in computed volume from two simulations, one with a solute present and another without. Thermodynamically, V° can also be determined as the pressure derivative of the free energy of solvation in the limit of infinite dilution. Both approaches are considered herein with the use of free energy perturbation (FEP) calculations to compute the necessary free energies of solvation at elevated pressures. Absolute and relative partial molar volumes are computed for benzene and benzene derivatives using the OPLS-AA force field. The mean unsigned error for all molecules is 2.8 cm(3) mol(-1). The present methodology should find use in many contexts such as the development and testing of force fields for use in computer simulations of organic and biomolecular systems, as a complement to related experimental studies, and to develop a deeper understanding of solute-solvent interactions.

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.

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.

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...

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.

Systems and Methods for Determining Inertial Navigation System Faults

Science.gov (United States)

Bharadwaj, Raj Mohan (Inventor); Bageshwar, Vibhor L. (Inventor); Kim, Kyusung (Inventor)

2017-01-01

An inertial navigation system (INS) includes a primary inertial navigation system (INS) unit configured to receive accelerometer measurements from an accelerometer and angular velocity measurements from a gyroscope. The primary INS unit is further configured to receive global navigation satellite system (GNSS) signals from a GNSS sensor and to determine a first set of kinematic state vectors based on the accelerometer measurements, the angular velocity measurements, and the GNSS signals. The INS further includes a secondary INS unit configured to receive the accelerometer measurements and the angular velocity measurements and to determine a second set of kinematic state vectors of the vehicle based on the accelerometer measurements and the angular velocity measurements. A health management system is configured to compare the first set of kinematic state vectors and the second set of kinematic state vectors to determine faults associated with the accelerometer or the gyroscope based on the comparison.

ALTERNATIVAS BIOMOLECULARES EN EL TRATAMIENTO DE LA OBESIDAD

Directory of Open Access Journals (Sweden)

Fernando Lizcano

2010-09-01

Full Text Available

Resumen

La obesidad se ha convertido en un problema de salud pública que cobija tanto a países desarrollados como a aquellos en vía de desarrollo. En la mayoría de los casos las políticas de salud no han tenido el efecto deseado para reducir la prevalencia de esta patología y muchos de los fármacos útiles para contrarrestar la obesidad no han podido continuar en el mercado debido a serios efectos secundarios. Algunas alternativas terapéuticas más agresivas como la cirugías reductivas han demostrado una utilidad restringida. Incluso, recientes observaciones han puesto de manifiesto las consecuencias a largo plazo de este tipo de intervenciones.

En la búsqueda de nuevas estrategias para el tratamiento de la obesidad se ha investigado, tanto en la propia célula grasa como en los genes que podrían ser modificados y cuya función está enfocada en regular el gasto calórico y la termogénesis adaptativa. Algunos de estos genes son modificados por factores de transcripción que pueden determinar la característica fenotípica de la célula grasa. Recientemente se ha observado que en la persona adulta es posible evidenciar vestigios de célula grasa parda que puede gastar energía en forma de calor y esta modificación podría ser una alternativa terapéutica en la obesidad. Nuestro grupo de investigación ha observado que mediante la modificación de la función de la proteína del retinoblastoma (pRb se pueden aumentar los genes que estimulan la pérdida calórica en el adipocito.

Palabras clave: Grasa Parda, Obesidad, transcripción, EID1, transdiferenciación

BIOMOLECULAR OPTIONS IN TREATING OBESITY

Abstract

Obesity is a public health issue for both developed and third world countries. Although many efforts have been made to reverse the trend of this prevalent pathology, no results have been obtained with public health policies in most cases. Furthermore, many medicines approved for

Application of Szilard-Chalmers labelling for the determination of biomolecular association in aqueous solutions

International Nuclear Information System (INIS)

Rack, E.P.; Blotcky, A.J.

1984-01-01

A radiometric recoil 130 I/sup m/ + 130 I atom tracer technique was developed for determining iodide ion-biomolecule association in liquid and frozen aqueous solutions of slightly soluble biomolecule solutes. It was found that the iodide ion associates with 5-iodouracil and 3-iodo-L-typrosine, but exhibits no association with uracil and 3,5-diiodo-L-tyrosine. 8 references, 1 table

System and method for determining stability of a neural system

Science.gov (United States)

Curtis, Steven A. (Inventor)

2011-01-01

Disclosed are methods, systems, and computer-readable media for determining stability of a neural system. The method includes tracking a function world line of an N element neural system within at least one behavioral space, determining whether the tracking function world line is approaching a psychological stability surface, and implementing a quantitative solution that corrects instability if the tracked function world line is approaching the psychological stability surface.

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.

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.

Protein fiber linear dichroism for structure determination and kinetics in a low-volume, low-wavelength couette flow cell.

Science.gov (United States)

Dafforn, Timothy R; Rajendra, Jacindra; Halsall, David J; Serpell, Louise C; Rodger, Alison

2004-01-01

High-resolution structure determination of soluble globular proteins relies heavily on x-ray crystallography techniques. Such an approach is often ineffective for investigations into the structure of fibrous proteins as these proteins generally do not crystallize. Thus investigations into fibrous protein structure have relied on less direct methods such as x-ray fiber diffraction and circular dichroism. Ultraviolet linear dichroism has the potential to provide additional information on the structure of such biomolecular systems. However, existing systems are not optimized for the requirements of fibrous proteins. We have designed and built a low-volume (200 microL), low-wavelength (down to 180 nm), low-pathlength (100 microm), high-alignment flow-alignment system (couette) to perform ultraviolet linear dichroism studies on the fibers formed by a range of biomolecules. The apparatus has been tested using a number of proteins for which longer wavelength linear dichroism spectra had already been measured. The new couette cell has also been used to obtain data on two medically important protein fibers, the all-beta-sheet amyloid fibers of the Alzheimer's derived protein Abeta and the long-chain assemblies of alpha1-antitrypsin polymers.

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.

Nano-motion dynamics are determined by surface-tethered selectin mechanokinetics and bond formation.

Directory of Open Access Journals (Sweden)

Brian J Schmidt

2009-12-01

-dimensional bond formation gained from flow cell assays might therefore be important to understand processes involving extended cellular interactions, such as immunological synapse formation. A biologically informative in silico system was created with minimal, high-confidence inputs. Incorporating random effects in surface separation through thermal motion enabled new deductions of the effects of surface-constrained biomolecular function. Important molecular information is embedded in the patterns and statistics of motion.

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

An Intelligent System for Determining Learning Style

Science.gov (United States)

Ozdemir, Ali; Alaybeyoglu, Aysegul; Mulayim, Naciye; Uysal, Muhammed

2018-01-01

In this study, an intelligent system which determines learning style of the students is developed to increase success in effective and easy learning. The importance of the proposed software system is to determine convenience degree of the student's learning style. Personal information form and Dunn Learning Style Preference Survey are used to…

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

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...

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.

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

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.

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 ...

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.

System for determining aerodynamic imbalance

Science.gov (United States)

Churchill, Gary B. (Inventor); Cheung, Benny K. (Inventor)

1994-01-01

A system is provided for determining tracking error in a propeller or rotor driven aircraft by determining differences in the aerodynamic loading on the propeller or rotor blades of the aircraft. The system includes a microphone disposed relative to the blades during the rotation thereof so as to receive separate pressure pulses produced by each of the blades during the passage thereof by the microphone. A low pass filter filters the output signal produced by the microphone, the low pass filter having an upper cut-off frequency set below the frequency at which the blades pass by the microphone. A sensor produces an output signal after each complete revolution of the blades, and a recording display device displays the outputs of the low pass filter and sensor so as to enable evaluation of the relative magnitudes of the pressure pulses produced by passage of the blades by the microphone during each complete revolution of the blades.

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

A Novel Attitude Determination System Aided by Polarization Sensor

Directory of Open Access Journals (Sweden)

Wei Zhi

2018-01-01

Full Text Available This paper aims to develop a novel attitude determination system aided by polarization sensor. An improved heading angle function is derived using the perpendicular relationship between directions of E-vector of linearly polarized light and solar vector in the atmospheric polarization distribution model. The Extended Kalman filter (EKF with quaternion differential equation as a dynamic model is applied to fuse the data from sensors. The covariance functions of filter process and measurement noises are deduced in detail. The indoor and outdoor tests are conducted to verify the validity and feasibility of proposed attitude determination system. The test results showed that polarization sensor is not affected by magnetic field, thus the proposed system can work properly in environments containing the magnetic interference. The results also showed that proposed system has higher measurement accuracy than common attitude determination system and can provide precise parameters for Unmanned Aerial Vehicle (UAV flight control. The main contribution of this paper is implementation of the EKF for incorporating the self-developed polarization sensor into the conventional attitude determination system. The real-world experiment with the quad-rotor proved that proposed system can work in a magnetic interference environment and provide sufficient accuracy in attitude determination for autonomous navigation of vehicle.

A Novel Attitude Determination System Aided by Polarization Sensor.

Science.gov (United States)

Zhi, Wei; Chu, Jinkui; Li, Jinshan; Wang, Yinlong

2018-01-09

This paper aims to develop a novel attitude determination system aided by polarization sensor. An improved heading angle function is derived using the perpendicular relationship between directions of E-vector of linearly polarized light and solar vector in the atmospheric polarization distribution model. The Extended Kalman filter (EKF) with quaternion differential equation as a dynamic model is applied to fuse the data from sensors. The covariance functions of filter process and measurement noises are deduced in detail. The indoor and outdoor tests are conducted to verify the validity and feasibility of proposed attitude determination system. The test results showed that polarization sensor is not affected by magnetic field, thus the proposed system can work properly in environments containing the magnetic interference. The results also showed that proposed system has higher measurement accuracy than common attitude determination system and can provide precise parameters for Unmanned Aerial Vehicle (UAV) flight control. The main contribution of this paper is implementation of the EKF for incorporating the self-developed polarization sensor into the conventional attitude determination system. The real-world experiment with the quad-rotor proved that proposed system can work in a magnetic interference environment and provide sufficient accuracy in attitude determination for autonomous navigation of vehicle.

Systems change for the social determinants of health.

Science.gov (United States)

Carey, Gemma; Crammond, Brad

2015-07-14

Inequalities in the distribution of the social determinants of health are now a widely recognised problem, seen as requiring immediate and significant action (CSDH. Closing the Gap in a Generation. Geneva: WHO; 2008; Marmot M. Fair Society, Healthy Lives: The Marmot Review. Strategic Review of Health Inequalitites in England Post-2010. London; 2010). Despite recommendations for action on the social determinants of health dating back to the 1980s, inequalities in many countries continue to grow. In this paper we provide an analysis of recommendations from major social determinants of health reports using the concept of 'system leverage points'. Increasingly, powerful and effective action on the social determinants of health is conceptualised as that which targets government action on the non-health issues which drive health outcomes. Recommendations for action from 6 major national reports on the social determinants of health were sourced. Recommendations from each report were coded against two frameworks: Johnston et al's recently developed Intervention Level Framework (ILF) and Meadow's seminal '12 places to intervene in a system' (Johnston LM, Matteson CL, Finegood DT. Systems Science and Obesity Policy: A Novel Framework for Analyzing and Rethinking Population-Level Planning. American journal of public health. 2014;(0):e1-e9; Meadows D. Thinking in Systems. USA: Sustainability Institute; 1999) (N = 166). Our analysis found several major changes over time to the types of recommendations being made, including a shift towards paradigmatic change and away from individual interventions. Results from Meadow's framework revealed a number of potentially powerful system intervention points that are currently underutilised in public health thinking regarding action on the social determinants of health. When viewed through a systems lens, it is evident that the power of an intervention comes not from where it is targeted, but rather how it works to create change within the

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.

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.

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.

High energy halogen atom reactions activated by nuclear transformations. Progress report, February 15, 1980-February 14, 1981

International Nuclear Information System (INIS)

1981-02-01

The stereochemistry of high energy 18 F, /sup 34m/Cl, and 76 Br substitution reactions involving enantiomeric molecules in the gas and condensed phase is studied. The gas to condensed state transition in halogen high energy chemistry, involving chlorine, bromine, and iodine activated by the (n,γ) and (I.T.) processes in halomethanes, saturated and unsaturated hydrocarbons is being investigated in more detail. Special attention is given to defining the nature of the enhancement yields in the condensed phase. High energy halogen reactions in liquid and frozen aqueous solutions of organic and biomolecular solutes are studied in an attempt to learn more about these reactions. The applications of high energy chemistry techniques and theory to neutron activation analysis of biological systems are being continued. Special attention is given to developing procedures for trace molecular determinations in biological systems. The applications of hot halogen atoms as indicators of solute-solute interactions in liquid and frozen aqueous solutions of halogenated bases and nucleosides are being developed. Experiments are designed to explain the mechanisms of the radioprotection offered biomolecular solutes trapped within the frozen ice lattice. Reactions of bromine and iodine activated by isomeric transition with halogenated biomolecular solutes in liquid and frozen aqueous solutions are studied. The high energy reactions of iodine with the isomers of pentene have been studied in low pressure gaseous systems employing additives and rare gas moderators and liquid systems. Reactivity of excited complex formation and structural effects of electrophilic iodine attack on the pi-bond systems are studied

High energy halogen atom reactions activated by nuclear transformations. Progress report, February 15, 1980-February 14, 1981

Energy Technology Data Exchange (ETDEWEB)

1981-02-01

The stereochemistry of high energy /sup 18/F, /sup 34m/Cl, and /sup 76/Br substitution reactions involving enantiomeric molecules in the gas and condensed phase is studied. The gas to condensed state transition in halogen high energy chemistry, involving chlorine, bromine, and iodine activated by the (n,..gamma..) and (I.T.) processes in halomethanes, saturated and unsaturated hydrocarbons is being investigated in more detail. Special attention is given to defining the nature of the enhancement yields in the condensed phase. High energy halogen reactions in liquid and frozen aqueous solutions of organic and biomolecular solutes are studied in an attempt to learn more about these reactions. The applications of high energy chemistry techniques and theory to neutron activation analysis of biological systems are being continued. Special attention is given to developing procedures for trace molecular determinations in biological systems. The applications of hot halogen atoms as indicators of solute-solute interactions in liquid and frozen aqueous solutions of halogenated bases and nucleosides are being developed. Experiments are designed to explain the mechanisms of the radioprotection offered biomolecular solutes trapped within the frozen ice lattice. Reactions of bromine and iodine activated by isomeric transition with halogenated biomolecular solutes in liquid and frozen aqueous solutions are studied. The high energy reactions of iodine with the isomers of pentene have been studied in low pressure gaseous systems employing additives and rare gas moderators and liquid systems. Reactivity of excited complex formation and structural effects of electrophilic iodine attack on the pi-bond systems are studied.

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....

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.

Supramolecular photochemistry of drugs in biomolecular environments.

Science.gov (United States)

Monti, Sandra; Manet, Ilse

2014-06-21

In this tutorial review we illustrate how the interaction of photoactive drugs/potential drugs with proteins or DNA in supramolecular complexes can determine the course of the reactions initiated by the drug absorbed photons, evidencing the mechanistic differences with respect to the solution conditions. We focus on photoprocesses, independent of oxygen, that lead to chemical modification of the biomolecules, with formation of new covalent bonds or cleavage of existing bonds. Representative systems are mainly selected from the literature of the last decade. The photoreactivity of some aryl propionic acids, (fluoro)quinolones, furocoumarins, metal coordination complexes, quinine-like compounds, naphthaleneimides and pyrenyl-peptides with proteins or DNA is discussed. The use of light for biomolecule photomodification, historically relevant to biological photosensitization processes and some forms of photochemotherapy, is nowadays becoming more and more important in the development of innovative methods in nanomedicine and biotechnology.

Attitude Determination Error Analysis System (ADEAS) mathematical specifications document

Science.gov (United States)

Nicholson, Mark; Markley, F.; Seidewitz, E.

1988-01-01

The mathematical specifications of Release 4.0 of the Attitude Determination Error Analysis System (ADEAS), which provides a general-purpose linear error analysis capability for various spacecraft attitude geometries and determination processes, are presented. The analytical basis of the system is presented. The analytical basis of the system is presented, and detailed equations are provided for both three-axis-stabilized and spin-stabilized attitude sensor models.

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.

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.

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.

Position and orientation determination system and method

Science.gov (United States)

Harpring, Lawrence J.; Farfan, Eduardo B.; Gordon, John R.; Jannik, Gerald T.; Foley, Trevor Q.

2017-06-14

A position determination system and method is provided that may be used for obtaining position and orientation information of a detector in a contaminated room. The system includes a detector, a sensor operably coupled to the detector, and a motor coupled to the sensor to move the sensor around the detector. A CPU controls the operation of the motor to move the sensor around the detector and determines distance and angle data from the sensor to an object. The method includes moving a sensor around the detector and measuring distance and angle data from the sensor to an object at incremental positions around the detector.

Consumer Preferences Determine Resilience of Ecological-Economic Systems

Directory of Open Access Journals (Sweden)

Stefan Baumgärtner

2011-12-01

Full Text Available We perform a model analysis to study the origins of limited resilience in coupled ecological-economic systems. We demonstrate that under open access to ecosystems for profit-maximizing harvesting forms, the resilience properties of the system are essentially determined by consumer preferences for ecosystem services. In particular, we show that complementarity and relative importance of ecosystem services in consumption may significantly decrease the resilience of (almost any given state of the system. We conclude that the role of consumer preferences and management institutions is not just to facilitate adaptation to, or transformation of, some natural dynamics of ecosystems. Rather, consumer preferences and management institutions are themselves important determinants of the fundamental dynamic characteristics of coupled ecological-economic systems, such as limited resilience.

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

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.

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

The evolution of sex ratios and sex-determining systems

NARCIS (Netherlands)

Uller, Tobias; Pen, Ido; Wapstra, Erik; Beukeboom, Leo W.; Komdeur, Jan

Sex determination is a fundamental process governed by diverse mechanisms. Sex ratio selection is commonly implicated in the evolution of sex-determining systems, although formal models are rare. Here, we argue that, although sex ratio selection can induce shifts in sex determination, genomic

Environmental Light and Its Relationship with Electromagnetic Resonances of Biomolecular Interactions, as Predicted by the Resonant Recognition Model

Directory of Open Access Journals (Sweden)

Irena Cosic

2016-06-01

Full Text Available The meaning and influence of light to biomolecular interactions, and consequently to health, has been analyzed using the Resonant Recognition Model (RRM. The RRM proposes that biological processes/interactions are based on electromagnetic resonances between interacting biomolecules at specific electromagnetic frequencies within the infra-red, visible and ultra-violet frequency ranges, where each interaction can be identified by the certain frequency critical for resonant activation of specific biological activities of proteins and DNA. We found that: (1 the various biological interactions could be grouped according to their resonant frequency into super families of these functions, enabling simpler analyses of these interactions and consequently analyses of influence of electromagnetic frequencies to health; (2 the RRM spectrum of all analyzed biological functions/interactions is the same as the spectrum of the sun light on the Earth, which is in accordance with fact that life is sustained by the sun light; (3 the water is transparent to RRM frequencies, enabling proteins and DNA to interact without loss of energy; (4 the spectrum of some artificial sources of light, as opposed to the sun light, do not cover the whole RRM spectrum, causing concerns for disturbance to some biological functions and consequently we speculate that it can influence health.

On Determinism in Modal Transition Systems

DEFF Research Database (Denmark)

Benes, Nikola; Kretinsky, Jan; Larsen, Kim Guldstrand

2009-01-01

Modal transition systems (MTS) is a formalism which extends the classical notion of labelled transition systems by introducing transitions of two types: must transitions that have to be present in any implementation of the MTS and may transitions that are allowed but not required. The MTS framewo....... In the present article, we provide a comprehensive account of the MTS framework in the deterministic setting. We study a number of problems previously considered on MTS and point out to what extend we can expect better results under the restriction of determinism....

A QM-MD simulation approach to the analysis of FRET processes in (bio)molecular systems. A case study: complexes of E. coli purine nucleoside phosphorylase and its mutants with formycin A.

Science.gov (United States)

Sobieraj, M; Krzyśko, K A; Jarmuła, A; Kalinowski, M W; Lesyng, B; Prokopowicz, M; Cieśla, J; Gojdź, A; Kierdaszuk, B

2015-04-01

Predicting FRET pathways in proteins using computer simulation techniques is very important for reliable interpretation of experimental data. A novel and relatively simple methodology has been developed and applied to purine nucleoside phosphorylase (PNP) complexed with a fluorescent ligand - formycin A (FA). FRET occurs between an excited Tyr residue (D*) and FA (A). This study aims to interpret experimental data that, among others, suggests the absence of FRET for the PNPF159A mutant in complex with FA, based on novel theoretical methodology. MD simulations for the protein molecule containing D*, and complexed with A, are carried out. Interactions of D* with its molecular environment are accounted by including changes of the ESP charges in S1, compared to S0, and computed at the SCF-CI level. FRET probability W F depends on the inverse six-power of the D*-A distance, R da . The orientational factor 0 < k(2) < 4 between D* and A is computed and included in the analysis. Finally W F is time-averaged over the MD trajectories resulting in its mean value. The red-shift of the tyrosinate anion emission and thus lack of spectral overlap integral and thermal energy dissipation are the reasons for the FRET absence in the studied mutants at pH 7 and above. The presence of the tyrosinate anion results in a competitive energy dissipation channel and red-shifted emission, thus in consequence in the absence of FRET. These studies also indicate an important role of the phenyl ring of Phe159 for FRET in the wild-type PNP, which does not exist in the Ala159 mutant, and for the effective association of PNP with FA. In a more general context, our observations point out very interesting and biologically important properties of the tyrosine residue in its excited state, which may undergo spontaneous deprotonation in the biomolecular systems, resulting further in unexpected physical and/or biological phenomena. Until now, this observation has not been widely discussed in the

On Macroscopic Quantum Phenomena in Biomolecules and Cells: From Levinthal to Hopfield

Directory of Open Access Journals (Sweden)

Dejan Raković

2014-01-01

Full Text Available In the context of the macroscopic quantum phenomena of the second kind, we hereby seek for a solution-in-principle of the long standing problem of the polymer folding, which was considered by Levinthal as (semiclassically intractable. To illuminate it, we applied quantum-chemical and quantum decoherence approaches to conformational transitions. Our analyses imply the existence of novel macroscopic quantum biomolecular phenomena, with biomolecular chain folding in an open environment considered as a subtle interplay between energy and conformation eigenstates of this biomolecule, governed by quantum-chemical and quantum decoherence laws. On the other hand, within an open biological cell, a system of all identical (noninteracting and dynamically noncoupled biomolecular proteins might be considered as corresponding spatial quantum ensemble of these identical biomolecular processors, providing spatially distributed quantum solution to a single corresponding biomolecular chain folding, whose density of conformational states might be represented as Hopfield-like quantum-holographic associative neural network too (providing an equivalent global quantum-informational alternative to standard molecular-biology local biochemical approach in biomolecules and cells and higher hierarchical levels of organism, as well.

Detection of Gene Interactions Based on Syntactic Relations

Directory of Open Access Journals (Sweden)

Mi-Young Kim

2008-01-01

Full Text Available Interactions between proteins and genes are considered essential in the description of biomolecular phenomena, and networks of interactions are applied in a system's biology approach. Recently, many studies have sought to extract information from biomolecular text using natural language processing technology. Previous studies have asserted that linguistic information is useful for improving the detection of gene interactions. In particular, syntactic relations among linguistic information are good for detecting gene interactions. However, previous systems give a reasonably good precision but poor recall. To improve recall without sacrificing precision, this paper proposes a three-phase method for detecting gene interactions based on syntactic relations. In the first phase, we retrieve syntactic encapsulation categories for each candidate agent and target. In the second phase, we construct a verb list that indicates the nature of the interaction between pairs of genes. In the last phase, we determine direction rules to detect which of two genes is the agent or target. Even without biomolecular knowledge, our method performs reasonably well using a small training dataset. While the first phase contributes to improve recall, the second and third phases contribute to improve precision. In the experimental results using ICML 05 Workshop on Learning Language in Logic (LLL05 data, our proposed method gave an F-measure of 67.2% for the test data, significantly outperforming previous methods. We also describe the contribution of each phase to the performance.

"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.

Molecular Models of Genetic and Organismic Structures

CERN Document Server

Baianu, I C

2004-01-01

In recent studies we showed that the earlier relational theories of organismic sets (Rashevsky,1967), Metabolic-Replication (M,R)-systems (Rosen,1958)and molecular sets (Bartholomay,1968) share a joint foundation that can be studied within a unified categorical framework of functional organismic structures (Baianu,1980. This is possible because all relational theories have a biomolecular basis, that is, complex structures such as genomes, cells,organs and biological organisms are mathematically represented in terms of biomolecular properties and entities,(that are often implicit in their representation axioms. The definition of organismic sets, for example, requires that certain essential quantities be determined from experiment: these are specified by special sets of values of general observables that are derived from physicochemical measurements(Baianu,1970; Baianu,1980; Baianu et al, 2004a.)Such observables are context-dependent and lead directly to natural transformations in categories and Topoi, that are...

Accuracy Constraint Determination in Fixed-Point System Design

Directory of Open Access Journals (Sweden)

Serizel R

2008-01-01

Full Text Available Most of digital signal processing applications are specified and designed with floatingpoint arithmetic but are finally implemented using fixed-point architectures. Thus, the design flow requires a floating-point to fixed-point conversion stage which optimizes the implementation cost under execution time and accuracy constraints. This accuracy constraint is linked to the application performances and the determination of this constraint is one of the key issues of the conversion process. In this paper, a method is proposed to determine the accuracy constraint from the application performance. The fixed-point system is modeled with an infinite precision version of the system and a single noise source located at the system output. Then, an iterative approach for optimizing the fixed-point specification under the application performance constraint is defined and detailed. Finally the efficiency of our approach is demonstrated by experiments on an MP3 encoder.

Biomolecular bases of the senescence process and cancer. A new approach to oncological treatment linked to ageing.

Science.gov (United States)

Badiola, Iker; Santaolalla, Francisco; Garcia-Gallastegui, Patricia; Ana, Sánchez-Del Rey; Unda, Fernando; Ibarretxe, Gaskon

2015-09-01

Human ageing is associated with a gradual decline in the physiological functions of the body at multiple levels and it is a key risk factor for many diseases, including cancer. Ageing process is intimately related to widespread cellular senescence, characterised by an irreversible loss of proliferative capacity and altered functioning associated with telomere attrition, accumulation of DNA damage and compromised mitochondrial and metabolic function. Tumour and senescent cells may be generated in response to the same stimuli, where either cellular senescence or transformation would constitute two opposite outcomes of the same degenerative process. This paper aims to review the state of knowledge on the biomolecular relationship between cellular senescence, ageing and cancer. Importantly, many of the cell signalling pathways that are found to be altered during both cellular senescence and tumourigenesis are regulated through shared epigenetic mechanisms and, therefore, they are potentially reversible. MicroRNAs are emerging as pivotal players linking ageing and cancer. These small RNA molecules have generated great interest from the point of view of future clinical therapy for cancer because successful experimental results have been obtained in animal models. Micro-RNA therapies for cancer are already being tested in clinical phase trials. These findings have potential importance in cancer treatment in aged people although further research-based knowledge is needed to convert them into an effective molecular therapies for cancer linked to ageing. Copyright © 2015 Elsevier B.V. All rights reserved.

Bacterial imbalance of the vaginal flora: a cytological and biomolecular concept of Gardnerella vaginalis

NARCIS (Netherlands)

Klomp, J.M.

2008-01-01

Since 1996 all women aged 30 to 60 years are invited for a cervical smear on a 5 year interval. KOPAC, the Dutch national coding system for cervical smears, introduced for determination of cervical abnormalities also evaluates the inflammatory status of the vaginal flora. In this system

21 CFR 864.7340 - Fibrinogen determination system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fibrinogen determination system. 864.7340 Section 864.7340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7340...

Buckling determination in reflected systems, program FLUXFIT

Energy Technology Data Exchange (ETDEWEB)

Sotic, O [Boris Kidric Institute of Nuclear Sciences Vinca, Beograd (Yugoslavia)

1971-07-01

An improvement in accuracy of determining radial and axial buckling from foil activation distributions measured in reflected cylindrical systems is given. resultant activities are fitted to radial and axial spatial functions derived from homogeneous diffusion theory. A Fortran program FLUXFIT based on the derived method is included. (author)

Determination of SMES capacity to enhance the dynamic stability of power system

International Nuclear Information System (INIS)

Shi, J.; Tang, Y.; Dai, T.; Ren, L.; Li, J.; Cheng, S.

2010-01-01

This paper proposes the principle of SMES capacity determination for power system stable operation. Adopting the energy function method, the mechanism of SMES damping power oscillation in the classical single-machine infinite-bus (SMIB) system is analyzed. The released kinetic energy during disturbance is the original of power system oscillation, which is taken as the principle of SMES capacity determination. Then, the influence of fault type, fault position, and fault clearing time on the SMES capacity determination are discussed. Using MATLAB simulation, the principle of SMES capacity determination is evaluated.

Analytical static structure factor for a two-component system ...

Indian Academy of Sciences (India)

Marwan Al-Raeei

2018-03-29

Mar 29, 2018 ... be useful in studying biomolecular fluids and other soft matter fluids. Keywords. Ornstein–Zernike ... partial structure factor; isothermal compressibility; soft matter. PACS No. 05.20.Jj. 1. ..... computing. Users need to have ...

System and method to determine electric motor efficiency using an equivalent circuit

Science.gov (United States)

Lu, Bin [Kenosha, WI; Habetler, Thomas G [Snellville, GA

2011-06-07

A system and method for determining electric motor efficiency includes a monitoring system having a processor programmed to determine efficiency of an electric motor under load while the electric motor is online. The determination of motor efficiency is independent of a rotor speed measurement. Further, the efficiency is based on a determination of stator winding resistance, an input voltage, and an input current. The determination of the stator winding resistance occurs while the electric motor under load is online.

NanoDLSay: a new platform technology for biomolecular detection and analysis using gold nanoparticle probes coupled with dynamic light scattering

Science.gov (United States)

Bogdanovic, Jelena; Huo, Qun

2010-04-01

Most analytical techniques that are routinely used in biomedical research for detection and quantification of biomolecules are time-consuming, expensive and labor-intensive, and there is always a need for rapid, affordable and convenient methods. Recently we have developed a new platform technology for biomolecular detection and analysis: NanoDLSay. NanoDLSay employs antibody-coated gold nanoparticles (GNPs) and dynamic light scattering, and correlates the specific increase in particle size after antigen-antibody interaction to the target antigen concentration. We applied this technology to develop an assay for rapid detection of actin, a protein widely used as a loading control in Western Blot analysis. GNPs were coated with two types of polyclonal anti-actin antibodies, and used in the assay to detect two types of actin: β- and bovine skeletal muscle actin in RIPA buffer. The results of our study revealed some complex aspects of actin binding characteristics, which depended on the type of actin reagent and anti-actin antibody used. A surprising finding was a reverse dose-response relationship between the actin concentration and the average particle size in the assay solution, which we attributed to the effect of RIPA buffer. Our results indicate that RIPA may also interfere in other types of nanoparticle-based assays, and that this interference deserves further study.

Determining In Situ Protein Conformation and Orientation from the Amide-I Sum-Frequency Generation Spectrum: Theory and Experiment

NARCIS (Netherlands)

Roeters, S.J.; van Dijk, C.N.; Torres Knoop, A.; Backus, E.H.G.; Campen, R.K.; Bonn, M.; Woutersen, S.

2013-01-01

Vibrational sum-frequency generation (VSFG) spectra of the amide-I band of proteins can give detailed insight into biomolecular processes near membranes. However, interpreting these spectra in terms of the conformation and orientation of a protein can be difficult, especially in the case of complex

Neutron scattering studies of the dynamics of biopolymer-water systems using pulsed-source spectrometers

Energy Technology Data Exchange (ETDEWEB)

Middendorf, H.D. [Univ. of Oxford (United Kingdom); Miller, A. [Stirling Univ., Stirling (United Kingdom)

1994-12-31

Energy-resolving neutron scattering techniques provide spatiotemporal data suitable for testing and refining analytical models or computer simulations of a variety of dynamical processes in biomolecular systems. This paper reviews experimental work on hydrated biopolymers at ISIS, the UK Pulsed Neutron Facility. Following an outline of basic concepts and a summary of the new instrumental capabilities, the progress made is illustrated by results from recent experiments in two areas: quasi- elastic scattering from highly hydrated polysaccharide gels (agarose and hyaluronate), and inelastic scattering from vibrational modes of slightly hydrated collagen fibers.

Neutron scattering studies of the dynamics of biopolymer-water systems using pulsed-source spectrometers

International Nuclear Information System (INIS)

Middendorf, H.D.; Miller, A.

1994-01-01

Energy-resolving neutron scattering techniques provide spatiotemporal data suitable for testing and refining analytical models or computer simulations of a variety of dynamical processes in biomolecular systems. This paper reviews experimental work on hydrated biopolymers at ISIS, the UK Pulsed Neutron Facility. Following an outline of basic concepts and a summary of the new instrumental capabilities, the progress made is illustrated by results from recent experiments in two areas: quasi- elastic scattering from highly hydrated polysaccharide gels (agarose and hyaluronate), and inelastic scattering from vibrational modes of slightly hydrated collagen fibers

Investigation of Diode Pumped Alkali Laser Atmospheric Transmission Using Tunable Diode Laser Absorption Spectroscopy

Science.gov (United States)

2012-09-01

Optics Letters, 28(23):2336–2338, 2003. 48. Lavan, M. “High Energy Laser Systems for Short Range Defense”. Acta Physica Polonica -Series A General Physics...able diode laser spectrometer for the remote sensing of vehicle emissions”. Spec- trochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 60...P. “A review of recent advances in semiconductor laser based gas mon- itors”. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 54

Study on the effect of nanoparticle bimetallic coreshell Au-Ag for sensitivity enhancement of biosensor based on surface plasmon resonance

International Nuclear Information System (INIS)

Widayanti; Abraha, K

2016-01-01

Bimetallic Au-Ag core-shell, a type of composite spherical nanoparticle consisting of a spherical Au core covered by Ag shell, have been used as active material for biomolecular analyte detection based on surface plasmon resonance (SPR) spectroscopy. SPR technology evolved into a key technology for characterization of biomolecular interaction. In this paper, we want to show the influence of nanoparticle bimettalic Au-Ag coreshell for optic respon of LSPR biosensor through attenuated total reflection (ATR) spectrum. The method consist of several steps begin from make a model LSPR system with Kretschmann configuration, dielectric function determination of composite bimetallic coreshell nanoparticle using effective medium theory approximation and the last is reflectivity calculation for size variation of core and shell bimetallic nanoparticle. Our result show that, by varying the radius of core and shell thickness, the peak of the reflectivity (ATR spectrum) shifted to the different angle of incident light and the addition of coreshell in SPR biosensor leads to enhancement the sensitivity. (paper)

High energy halogen atom reactions activated by nuclear transformations. Progress report, February 15-December 31, 1984

International Nuclear Information System (INIS)

1985-01-01

Energetic halogen atoms or ions, activated by various nuclear transformations are studied in gas, high pressure and condensed phase saturated and unsaturated hydrocarbons, halomethanes, and liquid and solid aqueous solutions of biomolecular and organic solutes in order to understand better the mechanisms and dynamics of high energy monovalent species. The experimental program and its goals remain the same, consisting of four interrelated areas: (1) The stereochemistry of energetic 18 F, /sup 34m/Cl, and 38 Cl substitution reactions with chiral molecules in the gas and condensed phase is studied. (2) The gas to condensed state transition in halogen high energy chemistry, involving energetic chlorine, bromine, and iodine reactions in halomethanes, saturated and unsaturated hydrocarbons and aqueous solutions of biomolecules and alkyl halides is being investigated in more detail. Current attention is given to defining the nature of the enhancement yields in the condensed phase. Specifically, energetic halogen reactions in liquid and frozen aqueous solutions or organic and biomolecular solutes are studied. (3) Reactions of bromine and iodine activated by isomeric transition with halogenated biomolecular and organic solutes in liquid and frozen aqueous solutions are being studied in an attempt to learn more about the activation events in the condensed phase. (4) The applications of hot chemistry techniques and theory to neutron activation analysis of biological systems are being continued. Current attention is given to developing procedures for trace molecular determinations in biological systems. The applications of hot halogen atoms as site indicators in liquid and frozen aqueous solutions of halogenated bases and nucleosides are currently being developed. 14 references

System of automized determination of charged particle trajectories in extended magnetic fields

International Nuclear Information System (INIS)

Toumanian, A.R.

1981-01-01

An automized system for the determination of particle trajectories by the floating current-carrying wire method is described. The system is able to determine the charged particle trajectories with the energy above 100 MeV in magnetic systems of any configuration and with track extent up to several tens metres with momentum resolution up to 3.10 -4 . The system efficiency makes 1500 tracks/hour on the average [ru

Alternative irradiation system for efficiency manganese bath determination

Energy Technology Data Exchange (ETDEWEB)

Passos Leite, Sandro, E-mail: sandro@ird.gov.b [Programa de Engenharia Nuclear/COPPE, Universidade Federal do Rio de Janeiro, Ilha do Fundao, Caixa Postal 68509, 21945-970, Rio de Janeiro, RJ (Brazil); Wagner Pereira, Walsan, E-mail: walsan@ird.gov.b [Instituto de Radioprotecao e Dosimetria LNMRI/IRD/CNEN, Av. Salvador Allende, s/no, Recreio dos Bandeirantes, CEP: 22780-160, Rio de Janeiro (Brazil); Xavier da Silva, Ademir, E-mail: ademir@con.ufrj.b [Programa de Engenharia Nuclear/COPPE, Universidade Federal do Rio de Janeiro, Ilha do Fundao, Caixa Postal 68509, 21945-970, Rio de Janeiro, RJ (Brazil); Simoes da Fonseca, Evaldo, E-mail: evaldo@ird.gov.b [Instituto de Radioprotecao e Dosimetria LNMRI/IRD/CNEN, Av. Salvador Allende, s/no, Recreio dos Bandeirantes, CEP: 22780-160, Rio de Janeiro (Brazil); Souza Patrao, Karla Cristina de, E-mail: karla@ird.gov.b [Instituto de Radioprotecao e Dosimetria LNMRI/IRD/CNEN, Av. Salvador Allende, s/no, Recreio dos Bandeirantes, CEP: 22780-160, Rio de Janeiro (Brazil)

2010-12-15

An alternative irradiation system, which works with a radionuclide neutron source and manganese sulphate solution volume have been proposed for efficiency determination of a Manganese Bath System (MBS). This irradiation system was designed by simulation with MCNP5 code, considering a californium neutron source in several manganese sulphate volumes and different neutron reflectors. Although its solution specific activity are less than those in nuclear reactors, the simulation results have showed that the irradiation system proposed takes a manganese neutron capture increase up to 200 times when it compared to manganese neutron capture from a MBS whose diameter is about 100 cm. That becomes possible to use those samples for some of the absolute specific activity measuring methods.

On the Role of London Dispersion Forces in Biomolecular Structure Determination

Czech Academy of Sciences Publication Activity Database

Kolář, Michal; Kubař, T.; Hobza, Pavel

2011-01-01

Roč. 115, č. 24 (2011), s. 8038-8046 ISSN 1520-6106 R&D Projects: GA MŠk LC512; GA ČR GAP208/11/0295 Grant - others:Korea Science and Ingineering Foundation(KR) R32-2008-000-10180-0; European Scince Found(XE) CZ.1.05/2.1.00/03.0058 Institutional research plan: CEZ:AV0Z40550506 Keywords : dispersion interaction * DNA * molecular dynamics Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.696, year: 2011

Mixing height determination using remote sensing systems. General remarks

Energy Technology Data Exchange (ETDEWEB)

Beyrich, F. [BTU Cottbus, LS Umweltmeteorologie, Cottbus (Germany)

1997-10-01

Remote sensing systems can be considered today as a real alternative to classical soundings with respect to the MH (mixing height) determination. They have the basic advantage to allow continuous monitoring of the ABL (atmospheric boundary layer). Some technical issues which limit their operational use at present should be solved in the near future (frequency allocation, eye safety, costs). Taking into account specific operating conditions and the formulated-above requirements of a sounding system to be used for MH determination it becomes obvious that none of the available systems meets all of them, i.e., the `Mixing height-meter` does not exist. Therefore, reliable MH determination under a wide variety of conditions can be achieved only by integrating different instruments into a complex sounding system. The S-profiles provide a suitable data base for MH estimation from all types of remote sensing instruments. The criteria to deduce MH-values from these profiles should consider the structure type and the evolution stage of the ABL as well as the shape of the profiles. A certain kind of harmonization concerning these criteria should be achieved. MH values derived automatically from remote sensing data appear to be not yet reliable enough for direct operational use, they should be in any case critically examined by a trained analyst. Contemporary mathematical methods (wavelet transforms, fuzzy logics) are supposed to allow considerable progress in this field in the near future. (au) 19 refs.

DETERMINATION OF EFFICIENCY OF THE CIRCUMFERENTIAL DRAINAGE SYSTEM

Directory of Open Access Journals (Sweden)

Maciej Kroll

2015-11-01

Full Text Available One of the potential alternatives to improve the stability coefficient for an embankment structure is to flatten the filtration curve. As a result, we obtain lower body forces triggering the potential landslide and more advantageous soil strength parameters, which counteract landslide movements. In the case of waste dumps lowering the phreatic surface of waters is achieved thanks to the construction of auxiliary drainage systems, meeting the guidelines for their safe operation. The aim of this paper is to indicate a method facilitating the determination of the actual position of the phreatic surface within the deposited sediments and the assessment of efficiency of the circumferential drainage system in the waste dump. It was decided in this study to apply cone penetration test CPTU. The CPTU made it possible to measure dissipation of excess water pressure in pores identifying drainage conditions, which were compared with the results of piezometric measurements. The results of these tests made it possible to monitor changes in the position of the depression curve of supernatant waters in dams and to determine the efficiency of the circumferential drainage system.

Phase modulated 2D HSQC-TOCSY for unambiguous assignment of overlapping spin systems

Science.gov (United States)

Singh, Amrinder; Dubey, Abhinav; Adiga, Satish K.; Atreya, Hanudatta S.

2018-01-01

We present a new method that allows one to unambiguously resolve overlapping spin systems often encountered in biomolecular systems such as peptides and proteins or in samples containing a mixture of different molecules such as in metabolomics. We address this problem using the recently proposed phase modulation approach. By evolving the 1H chemical shifts in a conventional two dimensional (2D) HSQC-TOCSY experiment for a fixed delay period, the phase/intensity of set of cross peaks belonging to one spin system are modulated differentially relative to those of its overlapping counterpart, resulting in their discrimination and recognition. The method thus accelerates the process of identification and resonance assignment of individual compounds in complex mixtures. This approach facilitated the assignment of molecules in the embryo culture medium used in human assisted reproductive technology.

14 CFR 1212.501 - Record systems determined to be exempt.

Science.gov (United States)

2010-01-01

... information systems. (F) To prevent disclosure of law enforcement techniques and procedures. (G) To avoid... enforcement information systems. (G) To prevent disclosure of law enforcement techniques and procedures. (H... for the purpose of determining suitability or eligibility for Federal civilian employment or access to...

Super-resolution biomolecular crystallography with low-resolution data.

Science.gov (United States)

Schröder, Gunnar F; Levitt, Michael; Brunger, Axel T

2010-04-22

X-ray diffraction plays a pivotal role in the understanding of biological systems by revealing atomic structures of proteins, nucleic acids and their complexes, with much recent interest in very large assemblies like the ribosome. As crystals of such large assemblies often diffract weakly (resolution worse than 4 A), we need methods that work at such low resolution. In macromolecular assemblies, some of the components may be known at high resolution, whereas others are unknown: current refinement methods fail as they require a high-resolution starting structure for the entire complex. Determining the structure of such complexes, which are often of key biological importance, should be possible in principle as the number of independent diffraction intensities at a resolution better than 5 A generally exceeds the number of degrees of freedom. Here we introduce a method that adds specific information from known homologous structures but allows global and local deformations of these homology models. Our approach uses the observation that local protein structure tends to be conserved as sequence and function evolve. Cross-validation with R(free) (the free R-factor) determines the optimum deformation and influence of the homology model. For test cases at 3.5-5 A resolution with known structures at high resolution, our method gives significant improvements over conventional refinement in the model as monitored by coordinate accuracy, the definition of secondary structure and the quality of electron density maps. For re-refinements of a representative set of 19 low-resolution crystal structures from the Protein Data Bank, we find similar improvements. Thus, a structure derived from low-resolution diffraction data can have quality similar to a high-resolution structure. Our method is applicable to the study of weakly diffracting crystals using X-ray micro-diffraction as well as data from new X-ray light sources. Use of homology information is not restricted to X

Saponification reaction system: a detailed mass transfer coefficient determination.

Science.gov (United States)

Pečar, Darja; Goršek, Andreja

2015-01-01

The saponification of an aromatic ester with an aqueous sodium hydroxide was studied within a heterogeneous reaction medium in order to determine the overall kinetics of the selected system. The extended thermo-kinetic model was developed compared to the previously used simple one. The reaction rate within a heterogeneous liquid-liquid system incorporates a chemical kinetics term as well as mass transfer between both phases. Chemical rate constant was obtained from experiments within a homogeneous medium, whilst the mass-transfer coefficient was determined separately. The measured thermal profiles were then the bases for determining the overall reaction-rate. This study presents the development of an extended kinetic model for considering mass transfer regarding the saponification of ethyl benzoate with sodium hydroxide within a heterogeneous reaction medium. The time-dependences are presented for the mass transfer coefficient and the interfacial areas at different heterogeneous stages and temperatures. The results indicated an important role of reliable kinetic model, as significant difference in k(L)a product was obtained with extended and simple approach.

Barcoded microchips for biomolecular assays.

Science.gov (United States)

Zhang, Yi; Sun, Jiashu; Zou, Yu; Chen, Wenwen; Zhang, Wei; Xi, Jianzhong Jeff; Jiang, Xingyu

2015-01-20

Multiplexed assay of analytes is of great importance for clinical diagnostics and other analytical applications. Barcode-based bioassays with the ability to encode and decode may realize this goal in a straightforward and consistent manner. We present here a microfluidic barcoded chip containing several sets of microchannels with different widths, imitating the commonly used barcode. A single barcoded microchip can carry out tens of individual protein/nucleic acid assays (encode) and immediately yield all assay results by a portable barcode reader or a smartphone (decode). The applicability of a barcoded microchip is demonstrated by human immunodeficiency virus (HIV) immunoassays for simultaneous detection of three targets (anti-gp41 antibody, anti-gp120 antibody, and anti-gp36 antibody) from six human serum samples. We can also determine seven pathogen-specific oligonucleotides by a single chip containing both positive and negative controls.

Synchronous fluorescence based biosensor for albumin determination by cooperative binding of fluorescence probe in a supra-biomolecular host-protein assembly.

Science.gov (United States)

Patra, Digambara

2010-01-15

A synchronous fluorescence probe based biosensor for estimation of albumin with high sensitivity and selectivity was developed. Unlike conventional fluorescence emission or excitation spectral measurements, synchronous fluorescence measurement offered exclusively a new synchronous fluorescence peak in the shorter wavelength range upon binding of chrysene with protein making it an easy identification tool for albumin determination. The cooperative binding of a fluorescence probe, chrysene, in a supramolecular host-protein assembly during various albumin assessments was investigated. The presence of supramolecular host molecules such as beta-cyclodextrin, curucurbit[6]uril or curucurbit[7]uril have little influence on sensitivity or limit of detection during albumin determination but reduced dramatically interference from various coexisting metal ion quenchers/enhancers. Using the present method the limit of detection for BSA and gamma-Globulin was found to be 0.005 microM which is more sensitive than reported values. Copyright 2009 Elsevier B.V. All rights reserved.

Differential solvation of intrinsically disordered linkers drives the formation of spatially organized droplets in ternary systems of linear multivalent proteins

Science.gov (United States)

Harmon, Tyler S.; Holehouse, Alex S.; Pappu, Rohit V.

2018-04-01

Intracellular biomolecular condensates are membraneless organelles that encompass large numbers of multivalent protein and nucleic acid molecules. The bodies assemble via a combination of liquid–liquid phase separation and gelation. A majority of condensates included multiple components and show multilayered organization as opposed to being well-mixed unitary liquids. Here, we put forward a simple thermodynamic framework to describe the emergence of spatially organized droplets in multicomponent systems comprising of linear multivalent polymers also known as associative polymers. These polymers, which mimic proteins and/or RNA have the architecture of domains or motifs known as stickers that are interspersed by flexible spacers known as linkers. Using a minimalist numerical model for a four-component system, we have identified features of linear multivalent molecules that are necessary and sufficient for generating spatially organized droplets. We show that differences in sequence-specific effective solvation volumes of disordered linkers between interaction domains enable the formation of spatially organized droplets. Molecules with linkers that are preferentially solvated are driven to the interface with the bulk solvent, whereas molecules that have linkers with negligible effective solvation volumes form cores in the core–shell architectures that emerge in the minimalist four-component systems. Our modeling has relevance for understanding the physical determinants of spatially organized membraneless organelles.

Multiplexed evaluation of capture agent binding kinetics using arrays of silicon photonic microring resonators.

Science.gov (United States)

Byeon, Ji-Yeon; Bailey, Ryan C

2011-09-07

High affinity capture agents recognizing biomolecular targets are essential in the performance of many proteomic detection methods. Herein, we report the application of a label-free silicon photonic biomolecular analysis platform for simultaneously determining kinetic association and dissociation constants for two representative protein capture agents: a thrombin-binding DNA aptamer and an anti-thrombin monoclonal antibody. The scalability and inherent multiplexing capability of the technology make it an attractive platform for simultaneously evaluating the binding characteristics of multiple capture agents recognizing the same target antigen, and thus a tool complementary to emerging high-throughput capture agent generation strategies.

Automated system for the determination of patterns of high-intensity LEDs

International Nuclear Information System (INIS)

Baly, L.; Bolaño, L.; Arteche, R.; Broco, Y.; Quesada, I.; Rodríguez, E.

2008-01-01

Determination of high-intensity LEDs lighting patterns is an important step for the simulation and planning of arrays of these devices configurations. Currently there are systems based on CCD cameras able to efficiently solve this problem, however the high cost of these is a limiting factor for use. Another limitation of CCD cameras, is that they are designed for light levels much lower than those produced by a high-intensity LED. In this paper we present an automated system for the determination of the intensity of LEDs based on the scan point to point patterns. The results of the analysis of a type of LED based on arrays of bars with built-in optical system is presented.

Development of special analytical system for determination of free acid

International Nuclear Information System (INIS)

Zhang Lihua; Wu Jizong; Liu Huanliang; Liu Quanwei; Fan Dejun; Su Tao

2008-01-01

The determination of free-acid plays an important role in spent fuel reprocessing analysis. Its work accounts for about 30% of all analytical work in reprocessing. It is necessary to study and develop a special fast analytical system for determination of free acid. The special analytical system is particularly applicable to determination of free acid in high-level radioactive environment, which is composed of an optical fiber spectrophotometer and an automatic sample-in device. Small sample-in volume needed, fast procedure, easy operation and physical protection are its advantages. All kinds of performance and parameters satisfy the requirements of spent fuel reprocessing control analysis. For long-distance determination, the optical fiber spectrophotometer is connected with an 4.5 meters long optical fiber. To resolve the change of 0.1 mol/L acidity, the measuring optical path is 2 cm. Mass of 10-20 μm in diameter optical fibers are assembled. The optical fiber probe is composed of a reflecting mirror and a concave mirror on the top of optical fibers. To eliminate the interference of external light, a stainless steel measuring chamber is used. The automatic sample-in device is composed of state valve, quantifying pump and pipe. The sample-in precision of 15 μl and 35 μl quantifying loops is better than 0.5%. The special analytical system takes less than 7 minutes to complete one measurement. The linear range is 0.5 mol/L-3.5 mol/L. The relative standard deviation is better than 2.0% when the concentration of the free acid is about 2.0 mol/L. For samples in different medium, the results are comparable with the method of pH titration of determining the free acid in reprocessing. (authors)

Determinant formula for solutions of the Garnier system and Padé approximation

International Nuclear Information System (INIS)

Mano, Toshiyuki

2012-01-01

It is known that a class of special solutions of the Garnier system is expressed by a determinant formula in terms of a certain specialization of the Schur functions with rectangular-shape partitions. Y Yamada showed that such a determinant formula for rational solutions of Riccati type can be derived by making use of the Padé approximation. In this paper, we extend Yamada’s method. We derive a determinant formula for transcendental solutions of Riccati type by showing that the Padé approximation can be utilized in order to construct a Schlesinger transformation between isomonodromic deformations. In addition, we show that this method is effective in generic solutions of the Garnier system and derive a determinant structure of them. (paper)

Determination of power system component parameters using nonlinear dead beat estimation method

Science.gov (United States)

Kolluru, Lakshmi

Power systems are considered the most complex man-made wonders in existence today. In order to effectively supply the ever increasing demands of the consumers, power systems are required to remain stable at all times. Stability and monitoring of these complex systems are achieved by strategically placed computerized control centers. State and parameter estimation is an integral part of these facilities, as they deal with identifying the unknown states and/or parameters of the systems. Advancements in measurement technologies and the introduction of phasor measurement units (PMU) provide detailed and dynamic information of all measurements. Accurate availability of dynamic measurements provides engineers the opportunity to expand and explore various possibilities in power system dynamic analysis/control. This thesis discusses the development of a parameter determination algorithm for nonlinear power systems, using dynamic data obtained from local measurements. The proposed algorithm was developed by observing the dead beat estimator used in state space estimation of linear systems. The dead beat estimator is considered to be very effective as it is capable of obtaining the required results in a fixed number of steps. The number of steps required is related to the order of the system and the number of parameters to be estimated. The proposed algorithm uses the idea of dead beat estimator and nonlinear finite difference methods to create an algorithm which is user friendly and can determine the parameters fairly accurately and effectively. The proposed algorithm is based on a deterministic approach, which uses dynamic data and mathematical models of power system components to determine the unknown parameters. The effectiveness of the algorithm is tested by implementing it to identify the unknown parameters of a synchronous machine. MATLAB environment is used to create three test cases for dynamic analysis of the system with assumed known parameters. Faults are

Social determinants of health inequalities: towards a theoretical perspective using systems science.

Science.gov (United States)

Jayasinghe, Saroj

2015-08-25

A systems approach offers a novel conceptualization to natural and social systems. In recent years, this has led to perceiving population health outcomes as an emergent property of a dynamic and open, complex adaptive system. The current paper explores these themes further and applies the principles of systems approach and complexity science (i.e. systems science) to conceptualize social determinants of health inequalities. The conceptualization can be done in two steps: viewing health inequalities from a systems approach and extending it to include complexity science. Systems approach views health inequalities as patterns within the larger rubric of other facets of the human condition, such as educational outcomes and economic development. This anlysis requires more sophisticated models such as systems dynamic models. An extension of the approach is to view systems as complex adaptive systems, i.e. systems that are 'open' and adapt to the environment. They consist of dynamic adapting subsystems that exhibit non-linear interactions, while being 'open' to a similarly dynamic environment of interconnected systems. They exhibit emergent properties that cannot be estimated with precision by using the known interactions among its components (such as economic development, political freedom, health system, culture etc.). Different combinations of the same bundle of factors or determinants give rise to similar patterns or outcomes (i.e. property of convergence), and minor variations in the initial condition could give rise to widely divergent outcomes. Novel approaches using computer simulation models (e.g. agent-based models) would shed light on possible mechanisms as to how factors or determinants interact and lead to emergent patterns of health inequalities of populations.

Method for determining efficiency in a liquid scintillation system

International Nuclear Information System (INIS)

Laney, B.H.

1975-01-01

In a liquid scintillation system utilizing plural photomultiplyier means, a method for determining efficiency of coincident pulse detection. Various incremental counting efficiency levels are associated with asymptotic functions in a two dimension matrix in which the abscissa and ordinate correspond to the pulse heights of each of a pair of coincident pulses from different photomultiplier means. An efficiency determining point is located in the matrix based on the sum of the pulse heights of each of the coincident pulses as well as on the amplitude of the smallest pulse of the coincident pulses. The single counting efficiency determining point is recorded as the level of efficiency at which the photomultiplier means detect scintillations that generate coincident pulses having pulse heights equal to those recorded. (Patent Office Record)

System for determining sizes of biological macromolecules

International Nuclear Information System (INIS)

Nelson, R.M.; Danby, P.C.

1987-01-01

An electrophoresis system for determining the sizes of radiolabelled biological macromolecules is described. It comprises a cell containing an electrophoresis gel and having at least one lane, a voltage source connected across the gel for effecting the movement of macromolecules in the lane, a detector fixed relative to the moving molecules for generating electrical pulses responsive to signals emitted by the radiolabelled molecules; a pulse processor for counting the pulse rate, and a computational device for comparing the pulse rate to a predetermined value. (author)

The determinants of medical technology adoption in different decisional systems: A systematic literature review.

Science.gov (United States)

Varabyova, Yauheniya; Blankart, Carl Rudolf; Greer, Ann Lennarson; Schreyögg, Jonas

2017-03-01

Studies of determinants of adoption of new medical technology have failed to coalesce into coherent knowledge. A flaw obscuring strong patterns may be a common habit of treating a wide range of health care innovations as a generic technology. We postulate three decisional systems that apply to different medical technologies with distinctive expertise, interest, and authority: medical-individualistic, fiscal-managerial, and strategic-institutional decisional systems. This review aims to examine the determinants of the adoption of medical technologies based on the corresponding decision-making system. We included quantitative and qualitative studies that analyzed factors facilitating or inhibiting the adoption of medical technologies. In total, 65 studies published between 1974 and 2014 met our inclusion criteria. These studies contained 688 occurrences of variables that were used to examine the adoption decisions, and we subsequently condensed these variables to 62 determinants in four main categories: organizational, individual, environmental, and innovation-related. The determinants and their empirical association with adoption were grouped and analyzed by the three decision-making systems. Although we did not identify substantial differences across the decision-making systems in terms of the direction of the determinants' influence on adoption, a clear pattern emerged in terms of the categories of determinants that were targeted in different decision-making systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular simulation study to examine the possibility of detecting collective motion in protein by inelastic neutron scattering

International Nuclear Information System (INIS)

Yasumasa, Joti; Nobuhiro, Go; Akio, Kitao; Nobuhiro, Go

2003-01-01

Inelastic and quasielastic neutron scattering gives the information on the dynamics of biological macromolecules. The combination of computer simulation with neutron scattering experiments allows us to characterize a wide range of dynamical phenomena in condensed phase bio-molecular systems. In this work, the dynamic structure factors in (Q,ω)-space were calculated by using the results of bio-molecular simulations. From the simulated inelastic neutron scattering spectra, we discuss the (Q,ω)-range and the resolution of a detector needed to observe function-related protein dynamics. (authors)

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.

Determination of ethanol using permanganate-CdS quantum dot chemiluminescence system.

Science.gov (United States)

Abolhasani, Jafar; Hassanzadeh, Javad

2015-08-01

A novel and highly sensitive chemiluminescence (CL) method for the determination of ethanol was developed based on the CdS quantum dots (QDs)-permanganate system. It was found that KMnO4 could directly oxidize CdS QDs in acidic media resulting in relatively high CL emission. A possible mechanism was proposed for this reaction based on UV/Vis absorption, fluorescence and the generated CL emission spectra. However, it was observed that ethanol had a remarkable inhibition effect on this system. This effect was exploited in the determination of ethanol within the concentration range 12-300 µg/L, with detection at 4.3 µg/L. In order to evaluate the capability of presented method, it was satisfactorily utilized in the determination of alcohol in real samples. Copyright © 2014 John Wiley & Sons, Ltd.

Experimental Determination of pK[subscript a] Values and Metal Binding for Biomolecular Compounds Using [superscript 31]P NMR Spectroscopy

Science.gov (United States)

Swartz, Mason A.; Tubergen, Philip J.; Tatko, Chad D.; Baker, Rachael A.

2018-01-01

This lab experiment uses [superscript 31]P NMR spectroscopy of biomolecules to determine pK[subscript a] values and the binding energies of metal/biomolecule complexes. Solutions of adenosine nucleotides are prepared, and a series of [superscript 31]P NMR spectra are collected as a function of pH and in the absence and presence of magnesium or…

System for prediction and determination of the sub critic multiplication

International Nuclear Information System (INIS)

Martinez, Aquilino S.; Pereira, Valmir; Silva, Fernando C. da

1997-01-01

It is presented a concept of a system which may be used to calculate and anticipate the subcritical multiplication of a PWR nuclear power plant. The system is divided into two different modules. The first module allows the theoretical prediction of the subcritical multiplication factor through the solution of the multigroup diffusion equation. The second module determines this factor based on the data acquired from the neutron detectors of a NPP external nuclear detection system. (author). 3 refs., 3 figs., 2 tabs

Determinants of Effective Internal Control System in Nigerian Banks ...

African Journals Online (AJOL)

Determinants of Effective Internal Control System in Nigerian Banks. ... (21) chief internal auditors of selected recapitalized banks currently operating in Port Harcourt. ... can be carried out, high level ethical standards should be enshrined in Nigerian banks to make internal control more effective. ... HOW TO USE AJOL.

Systematic errors of EIT systems determined by easily-scalable resistive phantoms.

Science.gov (United States)

Hahn, G; Just, A; Dittmar, J; Hellige, G

2008-06-01

We present a simple method to determine systematic errors that will occur in the measurements by EIT systems. The approach is based on very simple scalable resistive phantoms for EIT systems using a 16 electrode adjacent drive pattern. The output voltage of the phantoms is constant for all combinations of current injection and voltage measurements and the trans-impedance of each phantom is determined by only one component. It can be chosen independently from the input and output impedance, which can be set in order to simulate measurements on the human thorax. Additional serial adapters allow investigation of the influence of the contact impedance at the electrodes on resulting errors. Since real errors depend on the dynamic properties of an EIT system, the following parameters are accessible: crosstalk, the absolute error of each driving/sensing channel and the signal to noise ratio in each channel. Measurements were performed on a Goe-MF II EIT system under four different simulated operational conditions. We found that systematic measurement errors always exceeded the error level of stochastic noise since the Goe-MF II system had been optimized for a sufficient signal to noise ratio but not for accuracy. In time difference imaging and functional EIT (f-EIT) systematic errors are reduced to a minimum by dividing the raw data by reference data. This is not the case in absolute EIT (a-EIT) where the resistivity of the examined object is determined on an absolute scale. We conclude that a reduction of systematic errors has to be one major goal in future system design.

Systematic errors of EIT systems determined by easily-scalable resistive phantoms

International Nuclear Information System (INIS)

Hahn, G; Just, A; Dittmar, J; Hellige, G

2008-01-01

We present a simple method to determine systematic errors that will occur in the measurements by EIT systems. The approach is based on very simple scalable resistive phantoms for EIT systems using a 16 electrode adjacent drive pattern. The output voltage of the phantoms is constant for all combinations of current injection and voltage measurements and the trans-impedance of each phantom is determined by only one component. It can be chosen independently from the input and output impedance, which can be set in order to simulate measurements on the human thorax. Additional serial adapters allow investigation of the influence of the contact impedance at the electrodes on resulting errors. Since real errors depend on the dynamic properties of an EIT system, the following parameters are accessible: crosstalk, the absolute error of each driving/sensing channel and the signal to noise ratio in each channel. Measurements were performed on a Goe-MF II EIT system under four different simulated operational conditions. We found that systematic measurement errors always exceeded the error level of stochastic noise since the Goe-MF II system had been optimized for a sufficient signal to noise ratio but not for accuracy. In time difference imaging and functional EIT (f-EIT) systematic errors are reduced to a minimum by dividing the raw data by reference data. This is not the case in absolute EIT (a-EIT) where the resistivity of the examined object is determined on an absolute scale. We conclude that a reduction of systematic errors has to be one major goal in future system design

Portable refrigerant charge meter and method for determining the actual refrigerant charge in HVAC systems

Science.gov (United States)

Gao, Zhiming; Abdelaziz, Omar; LaClair, Tim L.

2017-08-08

A refrigerant charge meter and a method for determining the actual refrigerant charge in HVAC systems are described. The meter includes means for determining an optimum refrigerant charge from system subcooling and system component parameters. The meter also includes means for determining the ratio of the actual refrigerant charge to the optimum refrigerant charge. Finally, the meter includes means for determining the actual refrigerant charge from the optimum refrigerant charge and the ratio of the actual refrigerant charge to the optimum refrigerant charge.

Procedures for Determining the Performance of Stand-Alone Photovoltaic Systems; TOPICAL

International Nuclear Information System (INIS)

DeBlasio, R.; Durand, S.; Hansen, R.; Hutchinson, P.; Kroposki, B.; McNutt, P.; Rosenthal, A.; Thomas, M.

1999-01-01

This document provides the procedures for determining the performance of stand-alone PV systems. The procedures in this document provide a common approach for evaluating whether a given PV system is suitable to perform the function for which it was designed and manufactured to accomplish, and whether it will provide adequate power to run the load. These procedures cover small stand-alone PV systems. They cover complete outdoor system testing. Test results are valid only for the system that is tested

The design of systems for the determination of plutonium by passive neutron counting

International Nuclear Information System (INIS)

Hooton, B.W.

1978-10-01

The properties of moderators and other materials commonly used in systems for determination of plutonium by passive neutron counting have been investigated. The neutron flux from spontaneous fission and (α,n) reactions has been evaluated and the design characteristics of a number of systems have been determined by Monte Carlo tracking of neutrons. (author)

Single-molecule pull-down (SiMPull) for new-age biochemistry: methodology and biochemical applications of single-molecule pull-down (SiMPull) for probing biomolecular interactions in crude cell extracts.

Science.gov (United States)

Aggarwal, Vasudha; Ha, Taekjip

2014-11-01

Macromolecular interactions play a central role in many biological processes. Protein-protein interactions have mostly been studied by co-immunoprecipitation, which cannot provide quantitative information on all possible molecular connections present in the complex. We will review a new approach that allows cellular proteins and biomolecular complexes to be studied in real-time at the single-molecule level. This technique is called single-molecule pull-down (SiMPull), because it integrates principles of conventional immunoprecipitation with the powerful single-molecule fluorescence microscopy. SiMPull is used to count how many of each protein is present in the physiological complexes found in cytosol and membranes. Concurrently, it serves as a single-molecule biochemical tool to perform functional studies on the pulled-down proteins. In this review, we will focus on the detailed methodology of SiMPull, its salient features and a wide range of biological applications in comparison with other biosensing tools. © 2014 WILEY Periodicals, Inc.

System and method for determining stator winding resistance in an AC motor

Science.gov (United States)

Lu, Bin [Kenosha, WI; Habetler, Thomas G [Snellville, GA; Zhang, Pinjia [Atlanta, GA; Theisen, Peter J [West Bend, WI

2011-05-31

A system and method for determining stator winding resistance in an AC motor is disclosed. The system includes a circuit having an input connectable to an AC source and an output connectable to an input terminal of an AC motor. The circuit includes at least one contactor and at least one switch to control current flow and terminal voltages in the AC motor. The system also includes a controller connected to the circuit and configured to modify a switching time of the at least one switch to create a DC component in an output of the system corresponding to an input to the AC motor and determine a stator winding resistance of the AC motor based on the injected DC component of the voltage and current.

A system dynamics model to determine products mix

Directory of Open Access Journals (Sweden)

Mahtab Hajghasem

2014-02-01

Full Text Available This paper presents an implementation of system dynamics model to determine appropriate product mix by considering various factors such as labor, materials, overhead, etc. for an Iranian producer of cosmetic and sanitary products. The proposed model of this paper considers three hypotheses including the relationship between product mix and profitability, optimum production capacity and having minimum amount of storage to take advantage of low cost production. The implementation of system dynamics on VENSIM software package has confirmed all three hypotheses of the survey and suggested that in order to reach better mix product, it is necessary to reach optimum production planning, take advantage of all available production capacities and use inventory management techniques.

Transportation of drug–gold nanocomposites by actinomyosin motor system

International Nuclear Information System (INIS)

Kaur, Harsimran; Chaudhary, Archana; Kaur, Inderpreet; Singh, Kashmir; Bharadwaj, Lalit M.

2011-01-01

Nanotechnology is playing an important role in drug delivery to overcome limitations of conventional drug delivery systems in terms of solubility, in vivo stability, pharmacokinetics, and bio-distribution. The controlled transportation of drug into the cell and within the cell is a major challenge to be addressed. Cellular molecular motors have been exploited for their cargo carrying capacity for various applications including engineering and health care. Combination of nanotechnology and biomolecular motors can address some of the challenges in drug delivery. In the present study, transportation of drug nanocomposites has been demonstrated. Nanocomposites of 6-mercaptopurine and levodopa drugs (cancer and Parkinson’s disease, respectively) were prepared with gold nanoparticles (GNPs) by covalent attachment and these nanocomposites were attached to actin filaments. These nanocomposites were in-turn transported by actin filaments on myosin tracks. Characterization of drug nanocomposites formation was done by UV–Vis spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, and confocal microscopy. GNP composites of 6-mercaptopurine and levodopa were formed by sulfide and amide bond formation, respectively. Average velocity of actin filament attached to nanocomposites was found to be 3.17 and 3.89 μm/s for levodopa and 6-mercaptopurine, respectively, as compared to actin filaments with velocity of 4.0–6.0 μm/s. Three concepts have been proposed for the study of drug transportation into the cell based on polycationic complex formation, interaction of actin with cellular myosin and Biomolecular Adaptor for Retrograde Transport (BART) technology. The aspects of this study heads toward the development of an approach to utilize molecular motors for nanoscale transportation endogenously.

Transportation of drug-gold nanocomposites by actinomyosin motor system

Science.gov (United States)

Kaur, Harsimran; Chaudhary, Archana; Kaur, Inderpreet; Singh, Kashmir; Bharadwaj, Lalit M.

2011-06-01

Nanotechnology is playing an important role in drug delivery to overcome limitations of conventional drug delivery systems in terms of solubility, in vivo stability, pharmacokinetics, and bio-distribution. The controlled transportation of drug into the cell and within the cell is a major challenge to be addressed. Cellular molecular motors have been exploited for their cargo carrying capacity for various applications including engineering and health care. Combination of nanotechnology and biomolecular motors can address some of the challenges in drug delivery. In the present study, transportation of drug nanocomposites has been demonstrated. Nanocomposites of 6-mercaptopurine and levodopa drugs (cancer and Parkinson's disease, respectively) were prepared with gold nanoparticles (GNPs) by covalent attachment and these nanocomposites were attached to actin filaments. These nanocomposites were in-turn transported by actin filaments on myosin tracks. Characterization of drug nanocomposites formation was done by UV-Vis spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, and confocal microscopy. GNP composites of 6-mercaptopurine and levodopa were formed by sulfide and amide bond formation, respectively. Average velocity of actin filament attached to nanocomposites was found to be 3.17 and 3.89 μm/s for levodopa and 6-mercaptopurine, respectively, as compared to actin filaments with velocity of 4.0-6.0 μm/s. Three concepts have been proposed for the study of drug transportation into the cell based on polycationic complex formation, interaction of actin with cellular myosin and Biomolecular Adaptor for Retrograde Transport (BART) technology. The aspects of this study heads toward the development of an approach to utilize molecular motors for nanoscale transportation endogenously.

Transportation of drug-gold nanocomposites by actinomyosin motor system

Energy Technology Data Exchange (ETDEWEB)

Kaur, Harsimran, E-mail: microsimbac@gmail.com; Chaudhary, Archana; Kaur, Inderpreet [Council of Scientific and Industrial Research (CSIR), Biomolecular Electronics and Nanotechnology Division (BEND), Central Scientific Instruments Organization - CSIO (India); Singh, Kashmir [Panjab University, Department of Biotechnology (India); Bharadwaj, Lalit M. [Council of Scientific and Industrial Research (CSIR), Biomolecular Electronics and Nanotechnology Division (BEND), Central Scientific Instruments Organization - CSIO (India)

2011-06-15

Nanotechnology is playing an important role in drug delivery to overcome limitations of conventional drug delivery systems in terms of solubility, in vivo stability, pharmacokinetics, and bio-distribution. The controlled transportation of drug into the cell and within the cell is a major challenge to be addressed. Cellular molecular motors have been exploited for their cargo carrying capacity for various applications including engineering and health care. Combination of nanotechnology and biomolecular motors can address some of the challenges in drug delivery. In the present study, transportation of drug nanocomposites has been demonstrated. Nanocomposites of 6-mercaptopurine and levodopa drugs (cancer and Parkinson's disease, respectively) were prepared with gold nanoparticles (GNPs) by covalent attachment and these nanocomposites were attached to actin filaments. These nanocomposites were in-turn transported by actin filaments on myosin tracks. Characterization of drug nanocomposites formation was done by UV-Vis spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, and confocal microscopy. GNP composites of 6-mercaptopurine and levodopa were formed by sulfide and amide bond formation, respectively. Average velocity of actin filament attached to nanocomposites was found to be 3.17 and 3.89 {mu}m/s for levodopa and 6-mercaptopurine, respectively, as compared to actin filaments with velocity of 4.0-6.0 {mu}m/s. Three concepts have been proposed for the study of drug transportation into the cell based on polycationic complex formation, interaction of actin with cellular myosin and Biomolecular Adaptor for Retrograde Transport (BART) technology. The aspects of this study heads toward the development of an approach to utilize molecular motors for nanoscale transportation endogenously.

New technique for determining unavailability of computer controlled safety systems

International Nuclear Information System (INIS)

Fryer, M.O.; Bruske, S.Z.

1984-04-01

The availability of a safety system for a fusion reactor is determined. A fusion reactor processes tritium and requires an Emergency Tritium Cleanup (ETC) system for accidental tritium releases. The ETC is computer controlled and because of its complexity, is an excellent candidate for this analysis. The ETC system unavailability, for preliminary untested software, is calculated based on different assumptions about operator response. These assumptions are: (a) the operator shuts down the system after the first indication of plant failure; (b) the operator shuts down the system after following optimized failure verification procedures; or (c) the operator is taken out of the decision process, and the computer uses the optimized failure verification procedures

Determination of cost effective waste management system receipt rates

International Nuclear Information System (INIS)

McKee, R.W.; Huber, H.D.

1991-01-01

A comprehensive logistics and cost analysis has been carried out to determine if there are potential benefits to the high-level waste management system for receipt rates other than the current 3000 MTU/yr design-basis. The analysis includes both a Repository-Only System and a Storage-Only System. Repository startup dates of 2010 and 2015 and MRS startup dates of 1988 and three years prior to the repository have been evaluated. Receipt rates ranging from 1,500 to 6, 000 MTU/yr have been considered. Higher receipt rates appear to be economically justified, for either system, minimum costs are found at a repository receipt rate of 6000 MTU/yr. However, the MRS receipt rate for minimum system costs depends on the MRS startup date. With a 1988 MRS and a 2010 repository, the added cost of providing the MRS is offset by at-reactor storage cost reductions and the total system cost of $10.0 billion is virtually the same as for the repository- only system. 9 refs., 8 figs., 3 tabs

Results of applications of DISKOT system and of RIA determination of progesterone

International Nuclear Information System (INIS)

Beranek, J.

1989-01-01

Milk for progesterone determination was taken from cows picked out for insemination, cows following insemination and cows with reproduction disorders. The samples were taken in test tubes containing potassium dichromate. Progesterone was determined by RIA of skimmed milk and the results were transmitted to the DISKOT system in the data processing centre. The use of the DISKOT system output and the monitoring of progesterone in milk by the RIA laboratory improved reproduction indexes of the herd under study. (E.J.). 2 tabs

Determination of Critical Parameters of Carbon Dioxide+ Butyraldehyde System with Different Compositions

Institute of Scientific and Technical Information of China (English)

ZHANG Jing-chang; GAO Xi-xin; CAO Wei-liang

2005-01-01

Supercritical carbon dioxide( SC-CO2 ) is considered in green chemistry as a substitute for conventional solvents in chemical reactions due to its environmentally benign character. Recently we have reported the homogeneous hydroformylation of propylene in supercritical carbon dioxide( SC-CO2 ), which is an example of this kind of application of carbon dioxide. The determination for the critical parameters of carbon dioxide + butyraldehyde mixtures is necessary for this reaction design which is the focus of the present paper. The critical parameters of the binary systems were determined via the static visual method at a constant volume with the molar fraction of butyraldehyde ranging from 1.0%to 2. 2% and the pressure ranging from 5 to 10 MPa. The experimental results show that the critical pressure and temperature increased with increasing the molar fraction of butyraldehyde. The bubble(dew) temperatures and the bubble (dew) pressures for the binary systems were also determined experimentally. The p-T Figures at different compositions of the binary systems were described. In addition, the critical compressibility factors Zc of the binary systems at different concentrations of n-butyraldehyde were calculated. It was found that the critical compressibility factor values of the binary systems decreased with increasing the molar fraction of n-butyraldehyde in the experimental range.

Consumer Adoption of Personal Health Record Systems: A Self-Determination Theory Perspective.

Science.gov (United States)

Assadi, Vahid; Hassanein, Khaled

2017-07-27

Personal Health Records (PHR) systems provide individuals with access and control over their health information and consequently can support individuals in becoming active participants, rather than passive recipients, in their own care process. In spite of numerous benefits suggested for consumers' utilizing PHR systems, research has shown that such systems are not yet widely adopted or well known to consumers. Bearing in mind the potential benefits of PHRs to consumers and their potential interest in these systems-and that similar to any other type of information system, adoption is a prerequisite for realizing the potential benefits of PHR systems-research is needed to understand how to enhance the adoption rates for PHR systems. This research seeks to understand how individuals' intentions to adopt PHR systems are affected by their self-determination in managing their own health-the extent of their ability to take an active role in managing their own health. As such, this research aims to develop and empirically validate a theoretical model that explains PHR systems adoption by the general public through the integration of theories from the information systems and psychology literatures. This research employs a cross-sectional survey method targeted at the Canadian general public without any prior experience in using PHR systems. A partial least squares approach to structural equation modeling was used to validate the proposed research model of this study (N=159). Individuals with higher levels of ability to manage their own health (self-determination) are more likely to adopt PHR systems since they have more positive perceptions regarding the use of such systems. Further, such self-determination is fueled by autonomy support from consumers' physicians as well as the consumers' personality trait of autonomy orientation. This study advances our theoretical understanding of PHR systems adoption. It also contributes to practice by providing insightful implications

Use of multilevel modeling for determining optimal parameters of heat supply systems

Science.gov (United States)

Stennikov, V. A.; Barakhtenko, E. A.; Sokolov, D. V.

2017-07-01

The problem of finding optimal parameters of a heat-supply system (HSS) is in ensuring the required throughput capacity of a heat network by determining pipeline diameters and characteristics and location of pumping stations. Effective methods for solving this problem, i.e., the method of stepwise optimization based on the concept of dynamic programming and the method of multicircuit optimization, were proposed in the context of the hydraulic circuit theory developed at Melentiev Energy Systems Institute (Siberian Branch, Russian Academy of Sciences). These methods enable us to determine optimal parameters of various types of piping systems due to flexible adaptability of the calculation procedure to intricate nonlinear mathematical models describing features of used equipment items and methods of their construction and operation. The new and most significant results achieved in developing methodological support and software for finding optimal parameters of complex heat supply systems are presented: a new procedure for solving the problem based on multilevel decomposition of a heat network model that makes it possible to proceed from the initial problem to a set of interrelated, less cumbersome subproblems with reduced dimensionality; a new algorithm implementing the method of multicircuit optimization and focused on the calculation of a hierarchical model of a heat supply system; the SOSNA software system for determining optimum parameters of intricate heat-supply systems and implementing the developed methodological foundation. The proposed procedure and algorithm enable us to solve engineering problems of finding the optimal parameters of multicircuit heat supply systems having large (real) dimensionality, and are applied in solving urgent problems related to the optimal development and reconstruction of these systems. The developed methodological foundation and software can be used for designing heat supply systems in the Central and the Admiralty regions in

Biomolecular and structural analyses of cauliflower-like DNAs by ultraviolet, circular dichroism, and fluorescence spectroscopies in comparison with natural DNA.

Science.gov (United States)

Gill, Pooria; Ranjbar, Bijan; Saber, Reza; Khajeh, Khosro; Mohammadian, Mehdi

2011-07-01

Cauliflower-like DNAs are stem-loop DNAs that are fabricated periodically in inverted repetitions from deoxyribonucleic acid phosphates (dNTPs) by loop-mediated isothermal amplification (LAMP). Cauliflower-like DNAs have ladder-shape behaviors on gel electrophoresis, and increasing the time of LAMP leads to multiplying the repetitions, stem-loops, and electrophoretic bands. Cauliflower-like DNAs were fabricated via LAMP using two loop primers, two bumper primers, dNTPs, a λ-phage DNA template, and a Bst DNA polymerase in 75- and 90-min periods. These times led to manufacturing two types of cauliflower-like DNAs with different contents of inverted repetitions and stem-loops, which were clearly indicated by two comparable electrophoresis patterns in agarose gel. LAMP-fabricated DNAs and natural dsB-DNA (salmon genomic DNA) were dialyzed in Gomori phosphate buffer (10 mM, pH 7.4) to be isolated from salts, nucleotides, and primers. Dialyzed DNAs were studied using UV spectroscopy, circular dichroism spectropolarimetry, and fluorescence spectrophotometry. Structural analyses indicated reduction of the molecular ellipticity and extinction coefficients in comparison with B-DNA. Also, cauliflower-like DNAs demonstrated less intrinsic and more extrinsic fluorescence in comparison with natural DNA. The overwinding and lengthening of the cauliflower-like configurations of LAMP DNAs led to changes in physical parameters of this type of DNA in comparison with natural DNA. The results obtained introduced new biomolecular characteristics of DNA macromolecules fabricated within a LAMP process and show the effects of more inverted repeats and stem-loops, which are manufactured by lengthening the process.

Determinants of bacterial communities in Canadian agroforestry systems.

Science.gov (United States)

Banerjee, Samiran; Baah-Acheamfour, Mark; Carlyle, Cameron N; Bissett, Andrew; Richardson, Alan E; Siddique, Tariq; Bork, Edward W; Chang, Scott X

2016-06-01

Land-use change is one of the most important factors influencing soil microbial communities, which play a pivotal role in most biogeochemical and ecological processes. Using agroforestry systems as a model, this study examined the effects of land uses and edaphic properties on bacterial communities in three agroforestry types covering a 270 km soil-climate gradient in Alberta, Canada. Our results demonstrate that land-use patterns exert stronger effects on soil bacterial communities than soil zones in these agroforestry systems. Plots with trees in agroforestry systems promoted greater bacterial abundance and to some extent species richness, which was associated with more nutrient-rich soil resources. While Acidobacteria, Actinobacteria and Alphaproteobacteria were the dominant bacterial phyla and subphyla across land uses, Arthrobacter, Acidobacteria_Gp16, Burkholderia, Rhodanobacter and Rhizobium were the keystone taxa in these agroforestry systems. Soil pH and carbon contents emerged as the major determinants of bacterial community characteristics. We found non-random co-occurrence and modular patterns of soil bacterial communities, and these patterns were controlled by edaphic factors and not their taxonomy. Overall, this study highlights the drivers and co-occurrence patterns of soil microbial communities in agroforestry systems. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Determining the number of kanbans for dynamic production systems: An integrated methodology

Directory of Open Access Journals (Sweden)

Özlem Uzun Araz

2016-08-01

Full Text Available Just-in-time (JIT is a management philosophy that reduces the inventory levels and eliminates manufacturing wastes by producing only the right quantity at the right time. A kanban system is one of the key elements of JIT philosophy. Kanbans are used to authorize production and to control movement of materials in JIT systems. In Kanban systems, the efficiency of the manufacturing system depends on several factors such as number of kanbans, container size etc. Hence, determining the number of kanbans is a critical decision in Kanban systems. The aim of this study is to develop a methodology that can be used in order to determine the number of kanbans in a dynamic production environment. In this methodology, the changes in system state is monitored in real time manner, and the number of the kanbans are dynamically re-arranged. The proposed methodology integrates simulation, neural networks and Mamdani type fuzzy inference system. The methodology is modelled in simulation environment and applied on a hypothetic production system. We also performed several comparisons for different control policies to show the effectiveness of the proposed methodology.

Radioimmunoassay determination of urinary prostaglandins in patients with progressive systemic sclerosis

International Nuclear Information System (INIS)

Ramirez P, P.; Erbessd, M.L.; Mares, G.; Recinos, G.; Graef S, A.; Lavalle, C.

1985-01-01

The results of urinary determinations of E-2 prostaglandines by radioimmunoassay (RIA) in 24-hour urine are presented for three groups: progressive systemic sclerotic patients with normotension and with elevated or normal APR, progressive systemic sclerotic patients with hypertension and with normal or low APR, control group of normal subjects. In a recent report of progressive systemic sclerosis in patients we demonstrated changes in the urine concentratrion of APR levels, sodium excretion and in total blood volume. Based on these findings we felt the need to perform quantifications of E-2 prostaglandines (PGE-2) in 24-hour recently taken urine samples stored at 70 0 and measure the sodium amounts excreted in the urine. We concluded that urinary determination of E-2 prostaglandines was the most suitable for our study as it allowed the establishment of relationships between APR, aldosterone and metabolic sodium balance. (author)

Simulation techniques for determining reliability and availability of technical systems

International Nuclear Information System (INIS)

Lindauer, E.

1975-01-01

The system is described in the form of a fault tree with components representing part functions of the system and connections which reproduce the logical structure of the system. Both have the states intact or failed, they are defined here as in the programme FESIVAR of the IRS. For the simulation of components corresponding to the given probabilities, pseudo-random numbers are applied; these are numbers whose sequence is determined by the producing algorithm, but which for the given purpose sufficiently exhibit the behaviour of randomly successive numbers. This method of simulation is compared with deterministic methods. (HP/LH) [de

Automated determination of asulam by enhanced chemiluminescence using luminol/peroxidase system.

Science.gov (United States)

Sánchez, Francisco García; Díaz, Aurora Navas; Bracho, Visitación; Aguilar, Alfonso; Algarra, Manuel

2009-01-01

A flow injection system with chemiluminescence detection for the determination of asulam, enhancer of the system luminol-H(2)O(2)-horseradish peroxidase, is proposed. The method shows a moderate selectivity against other pesticides usually present in formulations of herbicides and in water. The procedure was applied to the determination of asulam in tap water samples and a recovery study was carried out in order to validate the method. The obtained results show acceptable recovery values (between 88.3 and 93.9%). The detection limit for asulam was 0.12 ng/mL. The precision of the method expressed as relative standard deviation was 1.55% (n = 8), at the 19 ng/mL level.

Advanced Microscopy Facility

Data.gov (United States)

Federal Laboratory Consortium — FUNCTION: Provides a facility for high-resolution studies of complex biomolecular systems. The goal is an understanding of how to engineer biomolecules for various...

Method of determining remedial control actions for a power system in an insecure state

DEFF Research Database (Denmark)

2013-01-01

A method of determining remedial control actions for a power system in an insecure and unstable operating condition is provided. The power system has a plurality of generators injecting power into a network and each generator has a generator injection impedance and a stability boundary in the inj......A method of determining remedial control actions for a power system in an insecure and unstable operating condition is provided. The power system has a plurality of generators injecting power into a network and each generator has a generator injection impedance and a stability boundary...

Decision Support System for Determining Scholarship Selection using an Analytical Hierarchy Process

Science.gov (United States)

Puspitasari, T. D.; Sari, E. O.; Destarianto, P.; Riskiawan, H. Y.

2018-01-01

Decision Support System is a computer program application that analyzes data and presents it so that users can make decision more easily. Determining Scholarship Selection study case in Senior High School in east Java wasn’t easy. It needed application to solve the problem, to improve the accuracy of targets for prospective beneficiaries of poor students and to speed up the screening process. This research will build system uses the method of Analytical Hierarchy Process (AHP) is a method that solves a complex and unstructured problem into its group, organizes the groups into a hierarchical order, inputs numerical values instead of human perception in comparing relative and ultimately with a synthesis determined elements that have the highest priority. The accuracy system for this research is 90%.

2017 publication guidelines for structural modelling of small-angle scattering data from biomolecules in solution: an update.

Science.gov (United States)

Trewhella, Jill; Duff, Anthony P; Durand, Dominique; Gabel, Frank; Guss, J Mitchell; Hendrickson, Wayne A; Hura, Greg L; Jacques, David A; Kirby, Nigel M; Kwan, Ann H; Pérez, Javier; Pollack, Lois; Ryan, Timothy M; Sali, Andrej; Schneidman-Duhovny, Dina; Schwede, Torsten; Svergun, Dmitri I; Sugiyama, Masaaki; Tainer, John A; Vachette, Patrice; Westbrook, John; Whitten, Andrew E

2017-09-01

In 2012, preliminary guidelines were published addressing sample quality, data acquisition and reduction, presentation of scattering data and validation, and modelling for biomolecular small-angle scattering (SAS) experiments. Biomolecular SAS has since continued to grow and authors have increasingly adopted the preliminary guidelines. In parallel, integrative/hybrid determination of biomolecular structures is a rapidly growing field that is expanding the scope of structural biology. For SAS to contribute maximally to this field, it is essential to ensure open access to the information required for evaluation of the quality of SAS samples and data, as well as the validity of SAS-based structural models. To this end, the preliminary guidelines for data presentation in a publication are reviewed and updated, and the deposition of data and associated models in a public archive is recommended. These guidelines and recommendations have been prepared in consultation with the members of the International Union of Crystallography (IUCr) Small-Angle Scattering and Journals Commissions, the Worldwide Protein Data Bank (wwPDB) Small-Angle Scattering Validation Task Force and additional experts in the field.

The inverse problem of determining several coefficients in a nonlinear Lotka–Volterra system

International Nuclear Information System (INIS)

Roques, Lionel; Cristofol, Michel

2012-01-01

In this paper, we prove a uniqueness result in the inverse problem of determining several non-constant coefficients of a system of two parabolic equations, which corresponds to a Lotka–Volterra competition model. Our result gives a sufficient condition for the uniqueness of the determination of four coefficients of the system. This sufficient condition only involves pointwise measurements of the solution (u, v) of the system and of the spatial derivative ∂u/∂x or ∂v/∂x of one component at a single point x 0 , during a time interval (0, ε). Our results are illustrated by numerical computations. (paper)

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.

Group Decision Support System Determination Of Best Employee Using Topsis And Borda

Directory of Open Access Journals (Sweden)

Made Arya Budhi

2017-07-01

Full Text Available Determining the best employee at Lombok Garden inteded to stimulate the performance of the hotel employees Lombok Garden. Improved performance of employees it will have a direct effect on the quality of hotel services. Employee performance appraisement are conducted by six assessors, namely the head of each department and consists of several criteria. Assessments will be difficult if done manually considering each appraiser has its own preferences in assessment. To solve that problem, we need a computer system that helps decision-making is a group decision support system (GDSS determination of the best employees in the hotel Lombok Garden.Group decision support system developed in this study using TOPSIS (Technique For Order Preference By Similiarity To Ideal Solution and Borda to assist decision-making group. TOPSIS method is used for decision-making in each appraiser, while the Borda method used to combine the results of each assessor's decision so as to obtain the final result of the best employees in Lombok Garden.Based on the final result of the system of determination of the best employees in the form of a ranking of the final value of each employee. The highest value will be used as a recommendation as the best employee at Lombok Garden.

Service Quality: A Main Determinant Factor for Health Information System Success in Low-resource Settings.

Science.gov (United States)

Tilahun, Binyam; Fritz, Fleur

2015-01-01

With the increasing implementation of different health information systems in developing countries, there is a growing need to measure the main determinants of their success. The results of this evaluation study on the determinants of HIS success in five low resource setting hospitals show that service quality is the main determinant factor for information system success in those kind of settings.

A method to determine the dampening system of control rod drop mechanism for PWR reactors

International Nuclear Information System (INIS)

Trindade, C.E.; Mattos, J.R.L. de; Perrotta, J.A.

1988-08-01

A method to determine the Control Assembly damping drop system (dashpot/guide tube) was developed. It's presented a theoretical model, an experimental device and the procedures to determine this system, which is used in PWR reactors. (author) [pt

18 CFR 301.4 - Exchange Period Average System Cost determination.

Science.gov (United States)

2010-04-01

... REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS FOR FEDERAL POWER MARKETING ADMINISTRATIONS AVERAGE... Period and extend through four (4) years after the Exchange Period. The load forecast for Contract System... Utility's ASC until the change in service territory takes place. (g) ASC determination for Consumer-owned...

Study for Determining the Testing Condition of Compressor and Turbine System

International Nuclear Information System (INIS)

Sri Sudadiyo

2009-01-01

Study for Determining the Testing Condition of Compressor and Turbine System. From the viewpoint of energy system and environment, the concept for nuclear reactors of the generation IV have good potential for electricity and heat generation devices in producing hydrogen. These gas cooled nuclear reactors employ turbine cycle in transferring the heat. To analyses that coolant system, it is proposed a model of compressor and turbine system with power 3 kW. The used working fluid was hydrogen that be burnt with air within combustion chamber, then be expanded through a turbine for getting shaft work that will be used in driving compressor and generator. This study is aimed to determine the optimum testing conditions of gas turbine system. The used method is by applying the balance equations of energy, mass, and momentum. Gas turbine and compressor were placed at the single shaft, in which it was about 55 percent of power output for running the compressor. Under the testing condition for the speed of 20305 rpm, it was obtained thermal efficiency of the turbine cycle approximate 18 % (equal to the Carnot efficiency ratio 65 %), so that it is properly developed for the development of nuclear power installation in supporting the electricity energy demand and it will be very promising for the future facility. (author)

Determination of Systems Suitable for Study as Monotectic Binary Metallic Alloy Solidification Models

Science.gov (United States)

Smith, J. E., Jr.

1983-01-01

Succinonitrile-water and diethylene glycol-ethyl salicylate are two transparent systems which have been studied as monotectic binary metallic alloy solidification models. Being transparent, these systems allow for the direct observations of phase transformations and solidification reactions. The objective was to develop a screening technique to find systems of interest and then experimentally measure those systems. The succinonitrile-water system was used to check the procedures. To simulate the phase diagram of the system, two computer programs which determine solid-liquid and liquid-liquid equilibria were obtained. These programs use the UNIFAC method to determine activity coefficients and together with several other programs were used to predict the phase diagram. An experimental apparatus was developed and the succinonitrile-water phase diagram measured. The diagram was compared to both the simulation and literature data. Substantial differences were found in the comparisons which serve to demonstrate the need for this procedure.

Development of a Model Protein Interaction Pair as a Benchmarking Tool for the Quantitative Analysis of 2-Site Protein-Protein Interactions.

Science.gov (United States)

Yamniuk, Aaron P; Newitt, John A; Doyle, Michael L; Arisaka, Fumio; Giannetti, Anthony M; Hensley, Preston; Myszka, David G; Schwarz, Fred P; Thomson, James A; Eisenstein, Edward

2015-12-01

A significant challenge in the molecular interaction field is to accurately determine the stoichiometry and stepwise binding affinity constants for macromolecules having >1 binding site. The mission of the Molecular Interactions Research Group (MIRG) of the Association of Biomolecular Resource Facilities (ABRF) is to show how biophysical technologies are used to quantitatively characterize molecular interactions, and to educate the ABRF members and scientific community on the utility and limitations of core technologies [such as biosensor, microcalorimetry, or analytic ultracentrifugation (AUC)]. In the present work, the MIRG has developed a robust model protein interaction pair consisting of a bivalent variant of the Bacillus amyloliquefaciens extracellular RNase barnase and a variant of its natural monovalent intracellular inhibitor protein barstar. It is demonstrated that this system can serve as a benchmarking tool for the quantitative analysis of 2-site protein-protein interactions. The protein interaction pair enables determination of precise binding constants for the barstar protein binding to 2 distinct sites on the bivalent barnase binding partner (termed binase), where the 2 binding sites were engineered to possess affinities that differed by 2 orders of magnitude. Multiple MIRG laboratories characterized the interaction using isothermal titration calorimetry (ITC), AUC, and surface plasmon resonance (SPR) methods to evaluate the feasibility of the system as a benchmarking model. Although general agreement was seen for the binding constants measured using solution-based ITC and AUC approaches, weaker affinity was seen for surface-based method SPR, with protein immobilization likely affecting affinity. An analysis of the results from multiple MIRG laboratories suggests that the bivalent barnase-barstar system is a suitable model for benchmarking new approaches for the quantitative characterization of complex biomolecular interactions.

Long-range interactions and parallel scalability in molecular simulations

NARCIS (Netherlands)

Patra, M.; Hyvönen, M.T.; Falck, E.; Sabouri-Ghomi, M.; Vattulainen, I.; Karttunen, M.E.J.

2007-01-01

Typical biomolecular systems such as cellular membranes, DNA, and protein complexes are highly charged. Thus, efficient and accurate treatment of electrostatic interactions is of great importance in computational modeling of such systems. We have employed the GROMACS simulation package to perform

Optical neural network system for pose determination of spinning satellites

Science.gov (United States)

Lee, Andrew; Casasent, David

1990-01-01

An optical neural network architecture and algorithm based on a Hopfield optimization network are presented for multitarget tracking. This tracker utilizes a neuron for every possible target track, and a quadratic energy function of neural activities which is minimized using gradient descent neural evolution. The neural net tracker is demonstrated as part of a system for determining position and orientation (pose) of spinning satellites with respect to a robotic spacecraft. The input to the system is time sequence video from a single camera. Novelty detection and filtering are utilized to locate and segment novel regions from the input images. The neural net multitarget tracker determines the correspondences (or tracks) of the novel regions as a function of time, and hence the paths of object (satellite) parts. The path traced out by a given part or region is approximately elliptical in image space, and the position, shape and orientation of the ellipse are functions of the satellite geometry and its pose. Having a geometric model of the satellite, and the elliptical path of a part in image space, the three-dimensional pose of the satellite is determined. Digital simulation results using this algorithm are presented for various satellite poses and lighting conditions.

Computer program determines chemical composition of physical system at equilibrium

Science.gov (United States)

Kwong, S. S.

1966-01-01

FORTRAN 4 digital computer program calculates equilibrium composition of complex, multiphase chemical systems. This is a free energy minimization method with solution of the problem reduced to mathematical operations, without concern for the chemistry involved. Also certain thermodynamic properties are determined as byproducts of the main calculations.

Determination of characteristics of feromagnetic material using modern data acquisition system

Directory of Open Access Journals (Sweden)

Koprivica Branko

2009-01-01

Full Text Available This paper describes the use of modern measuring and data acquisition system for determining characteristics of feromagnetic material. For this purpose data acquisition card NI USB-6009, PC with data acquisition software and fluxmeter Electrical Steel Measuring System MPG 100 D were used. Based on the results obtained by measurements the modeling of hysteresis loop is performed by using appropriate mathematical model.

GNSS-based Road Charging Systems - Assessment of Vehicle Location Determination

DEFF Research Database (Denmark)

Zabic, Martina

the collected data from the experiment, in its original for, as it would be used as input for the automated charge calculation process in a road charging system. Furthermore, new methodologies are developed for assessing the performance of the vehicle location determination function in terms of data reliability...

Photogrammetry System and Method for Determining Relative Motion Between Two Bodies

Science.gov (United States)

Miller, Samuel A. (Inventor); Severance, Kurt (Inventor)

2014-01-01

A photogrammetry system and method provide for determining the relative position between two objects. The system utilizes one or more imaging devices, such as high speed cameras, that are mounted on a first body, and three or more photogrammetry targets of a known location on a second body. The system and method can be utilized with cameras having fish-eye, hyperbolic, omnidirectional, or other lenses. The system and method do not require overlapping fields-of-view if two or more cameras are utilized. The system and method derive relative orientation by equally weighting information from an arbitrary number of heterogeneous cameras, all with non-overlapping fields-of-view. Furthermore, the system can make the measurements with arbitrary wide-angle lenses on the cameras.

Determination of cost effective waste management system receipt rates

International Nuclear Information System (INIS)

McKee, R.W.; Huber, H.D.

1991-01-01

A comprehensive logistics and cost analysis has been carried out to determine if there are potential benefits to the high-level waste management system for receipt rates other than the current 3,000 MTU/yr design-basis receipt rate. The scope of the analysis includes both a Repository-Only System and a Storage-Only or Basic MRS System. To allow for current uncertainties in facility startup scheduling, cases considering repository startup dates of 2010 and 2015 and MRS startup dates of 1998 and three years prior to the repository have been evaluated. Receipt rates ranging from 1,500 to 6,000 MTU/yr have been considered for both the MRS and the repository. Higher receipt rates appear to be economically justified for both the repository and an MRS. For a repository-only system, minimum costs are found at a repository receipt rate of 6,000 MTU/yr. When a storage-only MRS is included in the system, minimum system costs are also achieved at a repository receipt rate of 6,000 MTU/yr. However, the MRS receipt rate for minimum system costs depends on the MRS startup date and ranges from 3,500 to 6,000 MTU/yr. With a 1998 MRS and a 2010 repository, the added cost of providing the MRS is offset by at-reactor storage cost reductions and the total system cost of $10.0 billion is virtually the same as for the repository-only system

High-Resolution Solid-State NMR Spectroscopy: Characterization of Polymorphism in Cimetidine, a Pharmaceutical Compound

Science.gov (United States)

Pacilio, Julia E.; Tokarski, John T.; Quiñones, Rosalynn; Iuliucci, Robbie J.

2014-01-01

High-resolution solid-state NMR (SSNMR) spectroscopy has many advantages as a tool to characterize solid-phase material that finds applications in polymer chemistry, nanotechnology, materials science, biomolecular structure determination, and others, including the pharmaceutical industry. The technology associated with achieving high resolution…

Metabolic syndrome in Iranian patients with systemic lupus erythematosus and its determinants.

Science.gov (United States)

Fatemi, Alimohammad; Ghanbarian, Azadeh; Sayedbonakdar, Zahra; Kazemi, Mehdi; Smiley, Abbas

2018-01-05

The aim of this study was to determine the prevalence of metabolic syndrome (MetS) in Iranian patients with systemic lupus erythematosus (SLE) and its determinants. In a cross-sectional study, 98 patients with SLE and 95 controls were enrolled. Prevalence of MetS was determined based on American Heart Association and National Heart, Lung, and Blood Institute (AHA/NHLBI) and 2009 harmonizing criteria. In addition, demographic features and lupus characteristics such as disease duration, pharmacological treatment, laboratory data, SLE disease activity index (SLEDAI), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage index (SDI) were recorded. The predictors of MetS were obtained by backward stepwise regression analysis. Using AHA/NHLBI, MetS was observed in 35 (35.7%) patients and 28 (29.8%) controls (P = 0.4). Using harmonizing criteria, MetS was observed in 37 (37.7%) patients and 33 (35.1%) controls (P = 0.7). There was no difference in frequency distribution of MetS components between the patients and the controls. In multivariate regression analysis, low C3, blood urea nitrogen (BUN), and body mass index were independent determinants of MetS in lupus patients. BUN, low C3, and body mass index were the major determinants of MetS in lupus patients.

Biomolecular markers of cancer-associated thromboembolism

Science.gov (United States)

Hanna, Diana L.; White, Richard H.; Wun, Ted

2013-01-01

Venous thromboembolism (VTE; deep venous thrombosis and pulmonary embolism) is associated with a poor prognosis in most malignancies and is a major cause of death among cancer patients. Universal anticoagulation for primary thromboprophylaxis in the outpatient setting is precluded by potential bleeding complications, especially without sufficient evidence that all patients would benefit from such prophylaxis. Therefore, appropriately targeting cancer patients for thromboprophylaxis is key to reducing morbidity and perhaps mortality. Predictive biomarkers could aid in identifying patients at high risk for VTE. Possible biomarkers for VTE include C-reactive protein, platelet and leukocyte counts, D-dimer and prothrombin fragment 1+2, procoagulant factor VIII, tissue factor, and soluble P-selectin. Evidence is emerging to support the use of risk assessment models in selecting appropriate candidates for primary thromboprophylaxis in the cancer setting. Further studies are needed to optimize these models and determine utility in reducing morbidity and mortality from cancer-associated thromboembolism. PMID:23522921

Determining Component Probability using Problem Report Data for Ground Systems used in Manned Space Flight

Science.gov (United States)

Monaghan, Mark W.; Gillespie, Amanda M.

2013-01-01

During the shuttle era NASA utilized a failure reporting system called the Problem Reporting and Corrective Action (PRACA) it purpose was to identify and track system non-conformance. The PRACA system over the years evolved from a relatively nominal way to identify system problems to a very complex tracking and report generating data base. The PRACA system became the primary method to categorize any and all anomalies from corrosion to catastrophic failure. The systems documented in the PRACA system range from flight hardware to ground or facility support equipment. While the PRACA system is complex, it does possess all the failure modes, times of occurrence, length of system delay, parts repaired or replaced, and corrective action performed. The difficulty is mining the data then to utilize that data in order to estimate component, Line Replaceable Unit (LRU), and system reliability analysis metrics. In this paper, we identify a methodology to categorize qualitative data from the ground system PRACA data base for common ground or facility support equipment. Then utilizing a heuristic developed for review of the PRACA data determine what reports identify a credible failure. These data are the used to determine inter-arrival times to perform an estimation of a metric for repairable component-or LRU reliability. This analysis is used to determine failure modes of the equipment, determine the probability of the component failure mode, and support various quantitative differing techniques for performing repairable system analysis. The result is that an effective and concise estimate of components used in manned space flight operations. The advantage is the components or LRU's are evaluated in the same environment and condition that occurs during the launch process.

RCSLK9: reactor coolant system leak rate determination for PWRs. User's guide

International Nuclear Information System (INIS)

Kirkpatrick, D.C.; Woodruff, R.W.; Holland, R.A.

1984-12-01

RCSLK9 is a computer program that was developed to analyze the leak tightness of the primary cooling system for any pressurized water reactor. From system conditions, water levels in tanks, and certain system design parameters, RCSLK9 calculates the loss of water from the cooling system and the increase of water in the leakage collection system during an arbitrary time interval. The program determines the system leak rates and displays or prints a report of the results. For initial application of the program at a reactor, RCSLK9 creates a file of system parameters and stores it for future use. RCSLK9 is written for use on the IBM PC

A teaching and learning sequence about the interplay of chance and determinism in nonlinear systems

International Nuclear Information System (INIS)

Stavrou, D; Duit, R; Komorek, M

2008-01-01

A teaching and learning sequence aimed at introducing upper secondary school students to the interplay between chance and determinism in nonlinear systems is presented. Three experiments concerning nonlinear systems (deterministic chaos, self-organization and fractals) and one experiment concerning linear systems are introduced. Thirty upper secondary students' capabilities and difficulties in understanding the scientific point of view were investigated, using a teaching experiment design. The results show that most students were capable of sound explanations concerning the interplay of chance and determinism in nonlinear systems

Determination of Minimum Data Set (MSD) in Echocardiography Reporting System to Exchange with Iran's Electronic Health Record (EHR) System.

Science.gov (United States)

Mahmoudvand, Zahra; Kamkar, Mehran; Shahmoradi, Leila; Nejad, Ahmadreza Farzaneh

2016-04-01

Determination of minimum data set (MDS) in echocardiography reports is necessary for documentation and putting information in a standard way, and leads to the enhancement of electrocardiographic studies through having access to precise and perfect reports and also to the development of a standard database for electrocardiographic reports. to determine the minimum data set of echocardiography reporting system to exchange with Iran's electronic health record (EHR) system. First, a list of minimum data set was prepared after reviewing texts and studying cardiac patients' records. Then, to determine the content validity of the prepared MDS, the expert views of 10 cardiologists and 10 health information management (HIM) specialists were obtained; to estimate the reliability of the set, test-retest method was employed. Finally, the data were analyzed using SPSS software. The highest degree of consensus was found for the following MDSs: patient's name and family name (5), accepting doctor's name and family name, familial death records due to cardiac disorders, the image identification code, mitral valve, aortic valve, tricuspid valve, pulmonary valve, left ventricle, hole, atrium valve, Doppler examination of ventricular and atrial movement models and diagnoses with an average of. To prepare a model of echocardiography reporting system to exchange with EHR system, creation a standard data set is the vital point. Therefore, based on the research findings, the minimum reporting system data to exchange with Iran's electronic health record system include information on entity, management, medical record, carried-out acts, and the main content of the echocardiography report, which the planners of reporting system should consider.

Adaptive resolution simulation of a biomolecule and its hydration shell: Structural and dynamical properties

International Nuclear Information System (INIS)

Fogarty, Aoife C.; Potestio, Raffaello; Kremer, Kurt

2015-01-01

A fully atomistic modelling of many biophysical and biochemical processes at biologically relevant length- and time scales is beyond our reach with current computational resources, and one approach to overcome this difficulty is the use of multiscale simulation techniques. In such simulations, when system properties necessitate a boundary between resolutions that falls within the solvent region, one can use an approach such as the Adaptive Resolution Scheme (AdResS), in which solvent particles change their resolution on the fly during the simulation. Here, we apply the existing AdResS methodology to biomolecular systems, simulating a fully atomistic protein with an atomistic hydration shell, solvated in a coarse-grained particle reservoir and heat bath. Using as a test case an aqueous solution of the regulatory protein ubiquitin, we first confirm the validity of the AdResS approach for such systems, via an examination of protein and solvent structural and dynamical properties. We then demonstrate how, in addition to providing a computational speedup, such a multiscale AdResS approach can yield otherwise inaccessible physical insights into biomolecular function. We use our methodology to show that protein structure and dynamics can still be correctly modelled using only a few shells of atomistic water molecules. We also discuss aspects of the AdResS methodology peculiar to biomolecular simulations

Adaptive resolution simulation of a biomolecule and its hydration shell: Structural and dynamical properties

Energy Technology Data Exchange (ETDEWEB)

Fogarty, Aoife C., E-mail: fogarty@mpip-mainz.mpg.de; Potestio, Raffaello, E-mail: potestio@mpip-mainz.mpg.de; Kremer, Kurt, E-mail: kremer@mpip-mainz.mpg.de [Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz (Germany)

2015-05-21

A fully atomistic modelling of many biophysical and biochemical processes at biologically relevant length- and time scales is beyond our reach with current computational resources, and one approach to overcome this difficulty is the use of multiscale simulation techniques. In such simulations, when system properties necessitate a boundary between resolutions that falls within the solvent region, one can use an approach such as the Adaptive Resolution Scheme (AdResS), in which solvent particles change their resolution on the fly during the simulation. Here, we apply the existing AdResS methodology to biomolecular systems, simulating a fully atomistic protein with an atomistic hydration shell, solvated in a coarse-grained particle reservoir and heat bath. Using as a test case an aqueous solution of the regulatory protein ubiquitin, we first confirm the validity of the AdResS approach for such systems, via an examination of protein and solvent structural and dynamical properties. We then demonstrate how, in addition to providing a computational speedup, such a multiscale AdResS approach can yield otherwise inaccessible physical insights into biomolecular function. We use our methodology to show that protein structure and dynamics can still be correctly modelled using only a few shells of atomistic water molecules. We also discuss aspects of the AdResS methodology peculiar to biomolecular simulations.

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

Determination of OB/OD/SF Emission Factors Using Unmanned Aerial Systems

Science.gov (United States)

A presentation to the Demilitarization Symposium. This proposal will present the methods of tethered aerostat and unmanned aerial system for collection of plume samples and determination of emission factors form open burning, open detonation, and static firing for weapon demilita...

Complex systems of biological interest stability under ionising radiations

International Nuclear Information System (INIS)

Maclot, Sylvain

2014-01-01

This PhD work presents the study of stability of molecular systems of biological interest in the gas phase after interaction with ionising radiations. The use of ionising radiation can probe the physical chemistry of complex systems at the molecular scale and thus consider their intrinsic properties. Beyond the fundamental aspect, this work is part of the overall understanding of radiation effects on living organisms and in particular the use of ionizing radiation in radiotherapy. Specifically, this study focused on the use of low-energy multiply charged ions (tens of keV) provided by the GANIL (Caen), which includes most of the experiments presented. In addition, experiments using VUV photons were also conducted at synchrotron ELETTRA (Trieste, Italy). The bio-molecular systems studied are amino acids and nucleic acid constituents. Using an experimental crossed beams device allows interaction between biomolecules and ionising radiation leads mainly to the ionization and fragmentation of the system. The study of its relaxation dynamics is by time-of-flight mass spectrometry coupled to a coincidences measurements method. It is shown that an approach combining experiment and theory allows a detailed study of the fragmentation dynamics of complex systems. The results indicate that fragmentation is generally governed by the Coulomb repulsion but the intramolecular rearrangements involve specific relaxation mechanisms. (author) [fr

Methodology and key determinants of building an efficient national innovation system of a country

Directory of Open Access Journals (Sweden)

Viktoriia Gurova

2015-12-01

Full Text Available The paper represents a research of theoretical principles for determining national innovation systems, as well as analyzes performance results displayed by national innovation systems of the leading countries in the global innovation space, while also describing characteristic features thereof and formulating recommendations for NIS build-up based on the same, implementation of which should serve as the basis of the national innovation system effective performance. It has been determined that at the current stage of global economy development such factors as science, technology and innovation play an important role in formation of a competitive economy. It has been established that the overall funding level with respect to science proves one of the key characteristics of an innovative country, and therefore NIS performance analysis was carried out based on the national expenditure indicator regarding research and development as well as on the country's position in the Global Innovation Index. The analysis carried out showed that the NISs of certain countries were more efficient than those of the others due to peculiarities of the innovative system elements that can be further referred to as determinants of building an effective national innovation system of a country

Optical Biosensors: A Revolution Towards Quantum Nanoscale Electronics Device Fabrication

Directory of Open Access Journals (Sweden)

D. Dey

2011-01-01

Full Text Available The dimension of biomolecules is of few nanometers, so the biomolecular devices ought to be of that range so a better understanding about the performance of the electronic biomolecular devices can be obtained at nanoscale. Development of optical biomolecular device is a new move towards revolution of nano-bioelectronics. Optical biosensor is one of such nano-biomolecular devices that has a potential to pave a new dimension of research and device fabrication in the field of optical and biomedical fields. This paper is a very small report about optical biosensor and its development and importance in various fields.

Determination of autoantibodies to annexin XI in systemic autoimmune diseases

DEFF Research Database (Denmark)

Jorgensen, C S; Levantino, G; Houen, Gunnar

2000-01-01

Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA...... experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His6-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out...... of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5...

Construction of an alternative system for the determination of sensitiveness of neutron radioisotopic primary source standardization system

International Nuclear Information System (INIS)

Leite, Sandro Passos; Silva, Ademir Xavier da; Castro, Leonardo Curvello de; Bittencourt, Guilherme Rodrigues

2009-01-01

This work studied, through the Monte Carlo modelling, a irradiation system for the aqueous solution MnSO 4 to be used in the proceeding of determination of counting efficiency of the manganese sulfate bath

78 FR 32427 - Notice of Issuance of Final Determination Concerning Multifunctional Digital Imaging Systems

Science.gov (United States)

2013-05-30

... multifunctional digital imaging systems for purposes of U.S. Government procurement. DATES: The final... Determination Concerning Multifunctional Digital Imaging Systems AGENCY: U.S. Customs and Border Protection... country of origin of certain multifunctional digital imaging systems. Based upon the facts presented, CBP...

Design of protein-responsive micro-sized hydrogels for self-regulating microfluidic systems

Science.gov (United States)

Hirayama, Mayu; Tsuruta, Kazuhiro; Kawamura, Akifumi; Ohara, Masayuki; Shoji, Kan; Kawano, Ryuji; Miyata, Takashi

2018-03-01

Diagnosis sensors using micro-total analysis systems (µ-TAS) have been developed for detecting target biomolecules such as proteins and saccharides because they are signal biomolecules for monitoring body conditions and diseases. In this study, biomolecularly stimuli-responsive micro-sized hydrogels that exhibited quick shrinkage in response to lectin concanavalinA (ConA) were prepared in a microchannel by photopolymerization using a fluorescence microscope. In preparing the micro-size hydrogels, glycosyloxyethyl methacrylate (GEMA) as a ligand monomer was copolymerized with a crosslinker in the presence of template ConA in molecular imprinting. The ConA-imprinted micro-hydrogel showed greater shrinkage in response to target ConA than nonimprinted micro-hydrogel. When a buffer solution was switched to an aqueous ConA solution in the Y-shaped microchannel, the flow rates changed quickly because of the responsive shrinkage of the micro-hydrogel prepared in the microchannel. These results suggest that the ConA-imprinted micro-hydrogel acted as a self-regulated microvalve in microfluidic systems.

Determination of the critical micelle concentration in simulations of surfactant systems

Energy Technology Data Exchange (ETDEWEB)

Santos, Andrew P.; Panagiotopoulos, Athanassios Z., E-mail: azp@princeton.edu [Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544 (United States)

2016-01-28

Alternative methods for determining the critical micelle concentration (cmc) are investigated using canonical and grand canonical Monte Carlo simulations of a lattice surfactant model. A common measure of the cmc is the “free” (unassociated) surfactant concentration in the presence of micellar aggregates. Many prior simulations of micellizing systems have observed a decrease in the free surfactant concentration with overall surfactant loading for both ionic and nonionic surfactants, contrary to theoretical expectations from mass-action models of aggregation. In the present study, we investigate a simple lattice nonionic surfactant model in implicit solvent, for which highly reproducible simulations are possible in both the canonical (NVT) and grand canonical (μVT) ensembles. We confirm the previously observed decrease of free surfactant concentration at higher overall loadings and propose an algorithm for the precise calculation of the excluded volume and effective concentration of unassociated surfactant molecules in the accessible volume of the solution. We find that the cmc can be obtained by correcting the free surfactant concentration for volume exclusion effects resulting from the presence of micellar aggregates. We also develop an improved method for determination of the cmc based on the maximum in curvature for the osmotic pressure curve determined from μVT simulations. Excellent agreement in cmc and other micellar properties between NVT and μVT simulations of different system sizes is observed. The methodological developments in this work are broadly applicable to simulations of aggregating systems using any type of surfactant model (atomistic/coarse grained) or solvent description (explicit/implicit)

Determination of the critical micelle concentration in simulations of surfactant systems.

Science.gov (United States)

Santos, Andrew P; Panagiotopoulos, Athanassios Z

2016-01-28

Alternative methods for determining the critical micelle concentration (cmc) are investigated using canonical and grand canonical Monte Carlo simulations of a lattice surfactant model. A common measure of the cmc is the "free" (unassociated) surfactant concentration in the presence of micellar aggregates. Many prior simulations of micellizing systems have observed a decrease in the free surfactant concentration with overall surfactant loading for both ionic and nonionic surfactants, contrary to theoretical expectations from mass-action models of aggregation. In the present study, we investigate a simple lattice nonionic surfactant model in implicit solvent, for which highly reproducible simulations are possible in both the canonical (NVT) and grand canonical (μVT) ensembles. We confirm the previously observed decrease of free surfactant concentration at higher overall loadings and propose an algorithm for the precise calculation of the excluded volume and effective concentration of unassociated surfactant molecules in the accessible volume of the solution. We find that the cmc can be obtained by correcting the free surfactant concentration for volume exclusion effects resulting from the presence of micellar aggregates. We also develop an improved method for determination of the cmc based on the maximum in curvature for the osmotic pressure curve determined from μVT simulations. Excellent agreement in cmc and other micellar properties between NVT and μVT simulations of different system sizes is observed. The methodological developments in this work are broadly applicable to simulations of aggregating systems using any type of surfactant model (atomistic/coarse grained) or solvent description (explicit/implicit).

Determination of the critical micelle concentration in simulations of surfactant systems

International Nuclear Information System (INIS)

Santos, Andrew P.; Panagiotopoulos, Athanassios Z.

2016-01-01

Alternative methods for determining the critical micelle concentration (cmc) are investigated using canonical and grand canonical Monte Carlo simulations of a lattice surfactant model. A common measure of the cmc is the “free” (unassociated) surfactant concentration in the presence of micellar aggregates. Many prior simulations of micellizing systems have observed a decrease in the free surfactant concentration with overall surfactant loading for both ionic and nonionic surfactants, contrary to theoretical expectations from mass-action models of aggregation. In the present study, we investigate a simple lattice nonionic surfactant model in implicit solvent, for which highly reproducible simulations are possible in both the canonical (NVT) and grand canonical (μVT) ensembles. We confirm the previously observed decrease of free surfactant concentration at higher overall loadings and propose an algorithm for the precise calculation of the excluded volume and effective concentration of unassociated surfactant molecules in the accessible volume of the solution. We find that the cmc can be obtained by correcting the free surfactant concentration for volume exclusion effects resulting from the presence of micellar aggregates. We also develop an improved method for determination of the cmc based on the maximum in curvature for the osmotic pressure curve determined from μVT simulations. Excellent agreement in cmc and other micellar properties between NVT and μVT simulations of different system sizes is observed. The methodological developments in this work are broadly applicable to simulations of aggregating systems using any type of surfactant model (atomistic/coarse grained) or solvent description (explicit/implicit)

75 FR 61509 - Notice of Issuance of Final Determination Concerning Solar Photovoltaic Panel Systems

Science.gov (United States)

2010-10-05

... Determination Concerning Solar Photovoltaic Panel Systems AGENCY: U.S. Customs and Border Protection, Department... Procurement; Title III, Trade Agreements Act of 1979; Country of Origin of solar photovoltaic panel system... solar photovoltaic (``PV'') panel systems contain both U.S. and foreign-origin raw materials and...

A STUDY ON DETERMINING THE REFERENCE SPREADING SEQUENCES FOR A DS/CDMACOMMUNICATION SYSTEM

Directory of Open Access Journals (Sweden)

Cebrail ÇİFTLİKLİ

2002-02-01

Full Text Available In a direct sequence/code division multiple access (DS/CDMA system, the role of the spreading sequences (codes is crucial since the multiple access interference (MAI is the main performance limitation. In this study, we propose an accurate criterion which enables the determination of the reference spreading codes which yield lower bit error rates (BER's in a given code set for a DS/CDMA system using despreading sequences weighted by stepping chip waveforms. The numerical results show that the spreading codes determined by the proposed criterion are the most suitable codes for using as references.

Determinants of performance of health systems concerning maternal and child health: a global approach.

Science.gov (United States)

Pinzón-Flórez, Carlos Eduardo; Fernández-Niño, Julián Alfredo; Ruiz-Rodríguez, Myriam; Idrovo, Álvaro J; Arredondo López, Abel Armando

2015-01-01

To assess the association of social determinants on the performance of health systems around the world. A transnational ecological study was conducted with an observation level focused on the country. In order to research on the strength of the association between the annual maternal and child mortality in 154 countries and social determinants: corruption, democratization, income inequality and cultural fragmentation, we used a mixed linear regression model for repeated measures with random intercepts and a conglomerate-based geographical analysis, between 2000 and 2010. Health determinants with a significant association on child mortality(corrupt government (Q3 vs Q1 = 83,05; 95%CI: 33,10 to 133). Improving access to water and sanitation systems, decreasing corruption in the health sector must become priorities in health systems. The ethno-linguistic cultural fragmentation and the detriment of democracy turn out to be two factors related to health results.

New formalism for determining excitation spectra of many-body systems

International Nuclear Information System (INIS)

Saito, S.; Zhang, S.B.; Louie, S.G.; Cohen, M.L.

1990-01-01

We present a new general formalism for determining the excitation spectrum of interacting many-body systems. The basic assumption is that the number of the excitations is equal to the number of sites. Within this approximation, it is shown that the density-density response functions with two different pure-imaginary energies determine the excitation spectrum. The method is applied to the valence electrons of sodium clusters of differing sizes in the time-dependent local-density approximation (TDLDA). A jellium-sphere background model is used for the ion cores. The excitation spectra obtained in this way represent well the excitation spectra given by the full TDLDA calculation along the real energy axis. Important collective modes are reproduced very well

Error Analysis of Determining Airplane Location by Global Positioning System

OpenAIRE

Hajiyev, Chingiz; Burat, Alper

1999-01-01

This paper studies the error analysis of determining airplane location by global positioning system (GPS) using statistical testing method. The Newton Rhapson method positions the airplane at the intersection point of four spheres. Absolute errors, relative errors and standard deviation have been calculated The results show that the positioning error of the airplane varies with the coordinates of GPS satellite and the airplane.

THE DETERMINANTS OF BANKING SYSTEM VULNERABILITY IN THE REPUBLIC OF MOLDOVA

Directory of Open Access Journals (Sweden)

Dorina CLICHICI

2013-12-01

Full Text Available A banking system is more vulnerable when there are felt more negative effects on this as a consequence of the global financial crisis events. In the context of the objective of enhancing financial stability and, in particular, limiting the likelihood of failure of the banking system it is useful to verify how the main characteristics which play a role for banking system vulnerability behaved in the case of the Republic of Moldova: system’s liquidity, capitalization, competition, diversification, presence of foreign banks, and wholesale funding. In order to determine how hard was hit the banking system of Moldova by the recent financial crisis in the article are analyzed quantitative and qualitative the above mentioned characteristics and identified the crisis effects on them.

Implementation of a low-cost, commercial orbit determination system

Science.gov (United States)

Corrigan, Jim

1994-01-01

Traditional satellite and launch control systems have consisted of custom solutions requiring significant development and maintenance costs. These systems have typically been designed to support specific program requirements and are expensive to modify and augment after delivery. The expanding role of space in today's marketplace combined with the increased sophistication and capabilities of modern satellites has created a need for more efficient, lower cost solutions to complete command and control systems. Recent technical advances have resulted in commercial-off-the-shelf products which greatly reduce the complete life-cycle costs associated with satellite launch and control system procurements. System integrators and spacecraft operators have, however, been slow to integrate these commercial based solutions into a comprehensive command and control system. This is due, in part, to a resistance to change and the fact that many available products are unable to effectively communicate with other commercial products. The United States Air Force, responsible for the health and safety of over 84 satellites via its Air Force Satellite Control Network (AFSCN), has embarked on an initiative to prove that commercial products can be used effectively to form a comprehensive command and control system. The initial version of this system is being installed at the Air Force's Center for Research Support (CERES) located at the National Test Facility in Colorado Springs, Colorado. The first stage of this initiative involved the identification of commercial products capable of satisfying each functional element of a command and control system. A significant requirement in this product selection criteria was flexibility and ability to integrate with other available commercial products. This paper discusses the functions and capabilities of the product selected to provide orbit determination functions for this comprehensive command and control system.

Atom-scale depth localization of biologically important chemical elements in molecular layers.

Science.gov (United States)

Schneck, Emanuel; Scoppola, Ernesto; Drnec, Jakub; Mocuta, Cristian; Felici, Roberto; Novikov, Dmitri; Fragneto, Giovanna; Daillant, Jean

2016-08-23

In nature, biomolecules are often organized as functional thin layers in interfacial architectures, the most prominent examples being biological membranes. Biomolecular layers play also important roles in context with biotechnological surfaces, for instance, when they are the result of adsorption processes. For the understanding of many biological or biotechnologically relevant phenomena, detailed structural insight into the involved biomolecular layers is required. Here, we use standing-wave X-ray fluorescence (SWXF) to localize chemical elements in solid-supported lipid and protein layers with near-Ångstrom precision. The technique complements traditional specular reflectometry experiments that merely yield the layers' global density profiles. While earlier work mostly focused on relatively heavy elements, typically metal ions, we show that it is also possible to determine the position of the comparatively light elements S and P, which are found in the most abundant classes of biomolecules and are therefore particularly important. With that, we overcome the need of artificial heavy atom labels, the main obstacle to a broader application of high-resolution SWXF in the fields of biology and soft matter. This work may thus constitute the basis for the label-free, element-specific structural investigation of complex biomolecular layers and biological surfaces.

A microcontroller-based microwave free-space measurement system for permittivity determination of lossy liquid materials.

Science.gov (United States)

Hasar, U C

2009-05-01

A microcontroller-based noncontact and nondestructive microwave free-space measurement system for real-time and dynamic determination of complex permittivity of lossy liquid materials has been proposed. The system is comprised of two main sections--microwave and electronic. While the microwave section provides for measuring only the amplitudes of reflection coefficients, the electronic section processes these data and determines the complex permittivity using a general purpose microcontroller. The proposed method eliminates elaborate liquid sample holder preparation and only requires microwave components to perform reflection measurements from one side of the holder. In addition, it explicitly determines the permittivity of lossy liquid samples from reflection measurements at different frequencies without any knowledge on sample thickness. In order to reduce systematic errors in the system, we propose a simple calibration technique, which employs simple and readily available standards. The measurement system can be a good candidate for industrial-based applications.

40 CFR 63.3165 - How do I determine the emission capture system efficiency?

Science.gov (United States)

2010-07-01

... system, and coating solvent flash-off and coating curing and drying occurs within the capture system. For... Compound (VOC) Released from Solventborne Automotive Coatings and Available for Removal in a VOC Control... Determining the Amount of Volatile Organic Compound (VOC) Released from Waterborne Automotive Coatings and...

Size determination of an equilibrium enzymic system by radiation inactivation

International Nuclear Information System (INIS)

Simon, P.; Swillens, S.; Dumont, J.E.

1982-01-01

Radiation inactivation of complex enzymic systems is currently used to determine the enzyme size and the molecular organization of the components in the system. An equilibrium model was simulated describing the regulation of enzyme activity by association of the enzyme with a regulatory unit. It is assumed that, after irradiation, the system equilibrates before the enzyme activity is assayed. The theoretical results show that the target-size analysis of these numerical data leads to a bad estimate of the enzyme size. Moreover, some implicit assumptions such as the transfer of radiation energy between non-covalently bound molecules should be verified before interpretation of target-size analysis. It is demonstrated that the apparent target size depends on the parameters of the system, namely the size and the concentration of the components, the equilibrium constant, the relative activities of free enzyme and enzymic complex, the existence of energy transfer, and the distribution of the components between free and bound forms during the irradiation. (author)

Study of an alternative system for manganese bath efficiency determination

International Nuclear Information System (INIS)

Leite, Sandro Passos

2010-01-01

An alternative irradiation system, using radioisotope neutron sources and a small MnSO 4 solution volume, was proposed m this work to determine the Manganese Bath System (MBS) efficiency. The irradiation system was characterized through simulations with the MCNP radiation transport code from the modeling of 252 Cf(f,n) and 238 PuBe(alpha,n) neutron sources in several MnSO 4 solution volumes and different neutron reflector medium for this solution. The parameter calculated in the simulations was the manganese neutron specific capture (MNSC), which is related to the MnSO 4 solution specific activity. From the proposed systems for 252 Cf (f, n) and 238 PuBe (alpha,n) the NSCM was increased hundred times, in relation with that achieved in the LN/LNMRI/IRD MBS system simulation when irradiated by each these neutron sources. During study for irradiation system characterization its concept was verified using a assemble of test irradiation (ATI), which were spherical glass cavities, with few centimeter in radius, filled with MnSO 4 solution, with and without presence of a neutron reflector medium. These TIA were used in four efficiency measurements and the average value was obtained. (author)

An Integrated Vision-Based System for Spacecraft Attitude and Topology Determination for Formation Flight Missions

Science.gov (United States)

Rogers, Aaron; Anderson, Kalle; Mracek, Anna; Zenick, Ray

2004-01-01

With the space industry's increasing focus upon multi-spacecraft formation flight missions, the ability to precisely determine system topology and the orientation of member spacecraft relative to both inertial space and each other is becoming a critical design requirement. Topology determination in satellite systems has traditionally made use of GPS or ground uplink position data for low Earth orbits, or, alternatively, inter-satellite ranging between all formation pairs. While these techniques work, they are not ideal for extension to interplanetary missions or to large fleets of decentralized, mixed-function spacecraft. The Vision-Based Attitude and Formation Determination System (VBAFDS) represents a novel solution to both the navigation and topology determination problems with an integrated approach that combines a miniature star tracker with a suite of robust processing algorithms. By combining a single range measurement with vision data to resolve complete system topology, the VBAFDS design represents a simple, resource-efficient solution that is not constrained to certain Earth orbits or formation geometries. In this paper, analysis and design of the VBAFDS integrated guidance, navigation and control (GN&C) technology will be discussed, including hardware requirements, algorithm development, and simulation results in the context of potential mission applications.

Molecular Dynamics Simulations of Kinetic Models for Chiral Dominance in Soft Condensed Matter

DEFF Research Database (Denmark)

Toxvaerd, Søren

2001-01-01

Molecular dynamics simulation, models for isomerization kinetics, origin of biomolecular chirality......Molecular dynamics simulation, models for isomerization kinetics, origin of biomolecular chirality...

System and method for determining an ammonia generation rate in a three-way catalyst

Science.gov (United States)

Sun, Min; Perry, Kevin L; Kim, Chang H

2014-12-30

A system according to the principles of the present disclosure includes a rate determination module, a storage level determination module, and an air/fuel ratio control module. The rate determination module determines an ammonia generation rate in a three-way catalyst based on a reaction efficiency and a reactant level. The storage level determination module determines an ammonia storage level in a selective catalytic reduction (SCR) catalyst positioned downstream from the three-way catalyst based on the ammonia generation rate. The air/fuel ratio control module controls an air/fuel ratio of an engine based on the ammonia storage level.

A strategy for determination of test intervals of k-out-of-n multi-channel systems

International Nuclear Information System (INIS)

Cho, S.; Jiang, J.

2007-01-01

State space models for determination of the optimal test frequencies for k-out-of-n multi channel systems are developed in this paper. The analytic solutions for the optimal surveillance test frequencies are derived using the Markov process technique. The solutions show that an optimal test frequency which maximizes the target probability can be determined by decomposing the system states to 3 states based on the system configuration and success criteria. Examples of quantification of the state probabilities and the optimal test frequencies of a three-channel system and a four-channel system with different success criteria are presented. The strategy for finding the optimal test frequency developed in this paper can generally be applicable to any k-out-of-n multi-channel standby systems that involve complex testing schemes. (author)

40 CFR 63.4165 - How do I determine the emission capture system efficiency?

Science.gov (United States)

2010-07-01

... when being moved between a spray booth and a curing oven. (b) If the capture system does not meet both... operation for which capture efficiency is being determined must be shut down, but all fans and blowers must... being determined must be shut down, but all fans and blowers must be operating normally. (4) For each...

Distance-based relative orbital elements determination for formation flying system

Science.gov (United States)

He, Yanchao; Xu, Ming; Chen, Xi

2016-01-01

The present paper deals with determination of relative orbital elements based only on distance between satellites in the formation flying system, which has potential application in engineering, especially suited for rapid orbit determination required missions. A geometric simplification is performed to reduce the formation configuration in three-dimensional space to a plane. Then the equivalent actual configuration deviating from its nominal design is introduced to derive a group of autonomous linear equations on the mapping between the relative orbital elements differences and distance errors. The primary linear equations-based algorithm is initially proposed to conduct the rapid and precise determination of the relative orbital elements without the complex computation, which is further improved by least-squares method with more distance measurements taken into consideration. Numerical simulations and comparisons with traditional approaches are presented to validate the effectiveness of the proposed methods. To assess the performance of the two proposed algorithms, accuracy validation and Monte Carlo simulations are implemented in the presence of noises of distance measurements and the leader's absolute orbital elements. It is demonstrated that the relative orbital elements determination accuracy of two approaches reaches more than 90% and even close to the actual values for the least-squares improved one. The proposed approaches can be alternates for relative orbit determination without assistance of additional facilities in engineering for their fairly high efficiency with accuracy and autonomy.

Design and Simulation of a Nano-Satellite Attitude Determination System

Science.gov (United States)

2009-12-01

4 D. SURVEY OF CUBESAT ATTITUDE DETERMINATION SYSTEMS... 6 1. Pumpkin IMI ADCS...imagery satellites are going through the same trend in resolution. They have improved in the past decade, from relatively low resolution at about 5m to...this is the nearly complete lack of a pre-packaged ADS. Until August of 2009, there was only one ADS available on the market. It was the Pumpkin

Noise-spectroscopy of multiqubit systems: Determining all their parameters by applying an external classical noise

Energy Technology Data Exchange (ETDEWEB)

Savel' ev, S., E-mail: S.Saveliev@lboro.ac.uk [Department of Physics, Loughborough University, Leicestershire LE11 3TU (United Kingdom); Advanced Science Institute, RIKEN, Wako-shi, Saitama 351-0198 (Japan); Zagoskin, A.M. [Department of Physics, Loughborough University, Leicestershire LE11 3TU (United Kingdom); Advanced Science Institute, RIKEN, Wako-shi, Saitama 351-0198 (Japan); Omelyanchouk, A.N. [Advanced Science Institute, RIKEN, Wako-shi, Saitama 351-0198 (Japan); B. Verkin Institute for Low Temperature Physics and Engineering, 61103 Kharkov (Ukraine); Nori, Franco [Advanced Science Institute, RIKEN, Wako-shi, Saitama 351-0198 (Japan); Physics Department, University of Michigan, Ann Arbor, MI 48109-1040 (United States)

2010-10-05

Imagine that you have several sets of two coupled qubits, but you do not know the parameters of their Hamitonians. How to determine these without resorting to the usual spectroscopy approach to the problem? Based on numerical modeling, we show that all the parameters of a system of two coupled qubits can be determined by applying to it an external classical noise and analyzing the Fourier spectrum of the elements of the system's density matrix. In particular, the interlevel spacings as well as the strength and sign of the qubit-qubit coupling can be determined this way.

Initial airworthiness determining the acceptability of new airborne systems

CERN Document Server

Gratton, Guy

2015-01-01

Designed as an introduction for both advanced students in aerospace engineering and existing aerospace engineers, this book covers both engineering theory and professional practice in establishing the airworthiness of new and modified aircraft. Initial Airworthiness includes information on: ·         how structural, handling, and systems evaluations are carried out; ·         the processes by which safety and fitness for purpose are determined; and ·         the use of both US and European unit systems Covering both civil and military practice and the current regulations and standards across Europe and North America, Initial Airworthiness will give the reader an understanding of how all the major aspects of an aircraft are certified, as well as providing a valuable source of reference for existing practitioners.

Comparison of attitude determination approaches using multiple Global Positioning System (GPS antennas

Directory of Open Access Journals (Sweden)

Wang Bing

2013-02-01

Full Text Available GPS-based attitude system is an important research field, since it is a valuable technique for the attitude determination of platforms. There exist two classes approaches for attitude determination using the GPS. The one determines attitude via baseline estimates in two frames, the other one solves for attitude by incorporating the attitude parameters directly into the GPS measurements. However, comparisons between these two classes approaches have been unexplored. First of all, two algorithms are introduced in detail which on behalf of these two kinds of approaches. Then we present numerical simulations demonstrating the performance of our algorithms and provide a comparison evaluating.

"Too big to fail" or "Too non-traditional to fail"?: The determinants of banks' systemic importance

OpenAIRE

Moore, Kyle; Zhou, Chen

2013-01-01

This paper empirically analyzes the determinants of banks' systemic importance. In constructing a measure on the systemic importance of financial institutions we find that size is a leading determinant. This confirms the usual "Too big to fail'' argument. Nevertheless, banks with size above a sufficiently high level have equal systemic importance. In addition to size, we find that the extent to which banks engage in non-traditional banking activities is also positively related to ...

Tutorial: Digital microfluidic biochips: Towards hardware/software co-design and cyber-physical system integration

DEFF Research Database (Denmark)

Ho, Tsung-Yi; Huang, Juinn-Dar; Pop, Paul

2013-01-01

This tutorial will first provide an overview of typical bio-molecular applications (market drivers) such as immunoassays, DNA sequencing, clinical chemistry, etc. Next, microarrays and various microfluidic platforms will be discussed. The next part of the tutorial will focus on electro-wetting-ba......This tutorial will first provide an overview of typical bio-molecular applications (market drivers) such as immunoassays, DNA sequencing, clinical chemistry, etc. Next, microarrays and various microfluidic platforms will be discussed. The next part of the tutorial will focus on electro......-wetting-based digital micro-fluidic biochips. The key idea here is to manipulate liquids as discrete droplets. A number of case studies based on representative assays and laboratory procedures will be interspersed in appropriate places throughout the tutorial. Basic concepts in micro-fabrication techniques will also...... be discussed. Attendees will next learn about CAD and reconfiguration aspects of digital microfluidic biochips. Synthesis tools will be described to map assay protocols from the lab bench to a droplet-based microfluidic platform and generate an optimized schedule of bioassay operations, the binding of assay...

Biomolecular Mechanisms of Pseudomonas aeruginosa and Escherichia coli Biofilm Formation

Science.gov (United States)

Laverty, Garry; Gorman, Sean P.; Gilmore, Brendan F.

2014-01-01

Pseudomonas aeruginosa and Escherichia coli are the most prevalent Gram-negative biofilm forming medical device associated pathogens, particularly with respect to catheter associated urinary tract infections. In a similar manner to Gram-positive bacteria, Gram-negative biofilm formation is fundamentally determined by a series of steps outlined more fully in this review, namely adhesion, cellular aggregation, and the production of an extracellular polymeric matrix. More specifically this review will explore the biosynthesis and role of pili and flagella in Gram-negative adhesion and accumulation on surfaces in Pseudomonas aeruginosa and Escherichia coli. The process of biofilm maturation is compared and contrasted in both species, namely the production of the exopolysaccharides via the polysaccharide synthesis locus (Psl), pellicle Formation (Pel) and alginic acid synthesis in Pseudomonas aeruginosa, and UDP-4-amino-4-deoxy-l-arabinose and colonic acid synthesis in Escherichia coli. An emphasis is placed on the importance of the LuxR homologue sdiA; the luxS/autoinducer-II; an autoinducer-III/epinephrine/norepinephrine and indole mediated Quorum sensing systems in enabling Gram-negative bacteria to adapt to their environments. The majority of Gram-negative biofilms consist of polysaccharides of a simple sugar structure (either homo- or heteropolysaccharides) that provide an optimum environment for the survival and maturation of bacteria, allowing them to display increased resistance to antibiotics and predation. PMID:25438014

Biomolecular Mechanisms of Pseudomonas aeruginosa and Escherichia coli Biofilm Formation

Directory of Open Access Journals (Sweden)

Garry Laverty

2014-07-01

Full Text Available Pseudomonas aeruginosa and Escherichia coli are the most prevalent Gram-negative biofilm forming medical device associated pathogens, particularly with respect to catheter associated urinary tract infections. In a similar manner to Gram-positive bacteria, Gram-negative biofilm formation is fundamentally determined by a series of steps outlined more fully in this review, namely adhesion, cellular aggregation, and the production of an extracellular polymeric matrix. More specifically this review will explore the biosynthesis and role of pili and flagella in Gram-negative adhesion and accumulation on surfaces in Pseudomonas aeruginosa and Escherichia coli. The process of biofilm maturation is compared and contrasted in both species, namely the production of the exopolysaccharides via the polysaccharide synthesis locus (Psl, pellicle Formation (Pel and alginic acid synthesis in Pseudomonas aeruginosa, and UDP-4-amino-4-deoxy-l-arabinose and colonic acid synthesis in Escherichia coli. An emphasis is placed on the importance of the LuxR homologue sdiA; the luxS/autoinducer-II; an autoinducer-III/epinephrine/norepinephrine and indole mediated Quorum sensing systems in enabling Gram-negative bacteria to adapt to their environments. The majority of Gram-negative biofilms consist of polysaccharides of a simple sugar structure (either homo- or heteropolysaccharides that provide an optimum environment for the survival and maturation of bacteria, allowing them to display increased resistance to antibiotics and predation.

Optimized computational method for determining the beta dose distribution using a multiple-element thermoluminescent dosimeter system

International Nuclear Information System (INIS)

Shen, L.; Levine, S.H.; Catchen, G.L.

1987-01-01

This paper describes an optimization method for determining the beta dose distribution in tissue, and it describes the associated testing and verification. The method uses electron transport theory and optimization techniques to analyze the responses of a three-element thermoluminescent dosimeter (TLD) system. Specifically, the method determines the effective beta energy distribution incident on the dosimeter system, and thus the system performs as a beta spectrometer. Electron transport theory provides the mathematical model for performing the optimization calculation. In this calculation, parameters are determined that produce calculated doses for each of the chip/absorber components in the three-element TLD system. The resulting optimized parameters describe an effective incident beta distribution. This method can be used to determine the beta dose specifically at 7 mg X cm-2 or at any depth of interest. The doses at 7 mg X cm-2 in tissue determined by this method are compared to those experimentally determined using an extrapolation chamber. For a great variety of pure beta sources having different incident beta energy distributions, good agreement is found. The results are also compared to those produced by a commonly used empirical algorithm. Although the optimization method produces somewhat better results, the advantage of the optimization method is that its performance is not sensitive to the specific method of calibration

Determination of Minimum Data Set (MSD) in Echocardiography Reporting System to Exchange with Iran’s Electronic Health Record (EHR) System

Science.gov (United States)

Mahmoudvand, Zahra; Kamkar, Mehran; Shahmoradi, Leila; Nejad, Ahmadreza Farzaneh

2016-01-01

Background: Determination of minimum data set (MDS) in echocardiography reports is necessary for documentation and putting information in a standard way, and leads to the enhancement of electrocardiographic studies through having access to precise and perfect reports and also to the development of a standard database for electrocardiographic reports. Aim: to determine the minimum data set of echocardiography reporting system to exchange with Iran’s electronic health record (EHR) system. Methods: First, a list of minimum data set was prepared after reviewing texts and studying cardiac patients’ records. Then, to determine the content validity of the prepared MDS, the expert views of 10 cardiologists and 10 health information management (HIM) specialists were obtained; to estimate the reliability of the set, test-retest method was employed. Finally, the data were analyzed using SPSS software. Results: The highest degree of consensus was found for the following MDSs: patient’s name and family name (5), accepting doctor’s name and family name, familial death records due to cardiac disorders, the image identification code, mitral valve, aortic valve, tricuspid valve, pulmonary valve, left ventricle, hole, atrium valve, Doppler examination of ventricular and atrial movement models and diagnoses with an average of. Conclusions: To prepare a model of echocardiography reporting system to exchange with EHR system, creation a standard data set is the vital point. Therefore, based on the research findings, the minimum reporting system data to exchange with Iran’s electronic health record system include information on entity, management, medical record, carried-out acts, and the main content of the echocardiography report, which the planners of reporting system should consider. PMID:27147803

Biomolecular electronics in the twenty-first century.

Science.gov (United States)

Phadke, R S

2001-01-01

A relentless decrease in the size of silicon-based microelectronics devices is posing problems. The most important among these are limitations imposed by quantum-size effects and instabilities introduced by the effects of thermal fluctuations. These inherent envisaged problems of present-day systems have prompted scientists to look for alternative options. Advancement in the understanding of natural systems such as photosynthetic apparatuses and genetic engineering has enabled attention to be focused on the use of biomolecules. Biomolecules have the advantages of functionality and specificity. The invention of scanning tunneling microscopy and atomic force microscopy has opened up the possibility of addressing and manipulating individual atoms and molecules. Realization of the power of self-assembly principles has opened a novel approach for designing and assembling molecular structures with desired intricate architecture. The utility of molecules such as DNA as a three-dimensional, high-density memory element and its capability for molecular computing have been fully recognized but not yet realized. More time and effort are necessary before devices that can transcend existing ones will become easily available. An overview of the current trends that are envisaged to give rich dividends in the next millennium are discussed.

Modernizing and Upgrading the Astrogeodetic Camera System for Determining Vertical Deflections

Science.gov (United States)

Albayrak, M.; Halicioglu, K.; Basoglu, B.; Ulug, R.; Ozludemir, M. T.; Deniz, R.

2017-12-01

The geoid is the equipotential surface of the Earth. Modeling the geoid with high accuracy is one of the critical issues in Geodesy. Development of geoid modeling is based on geodetic, gravimetric and astrogeodetic techniques. In order to reach the intended accuracy, deflection of the vertical (VD) components, which is obtained by the astrogeodetic techniques, can be used. VD is also very important for providing valuable information on the structure of Earth's gravity field. For this reason, astrogeodetic observations were essential gravity field observables and used for astrogeodetic geoid determinations. Scientists in several countries have developed modern instruments to measure vertical deflections. One of those instruments, namely Astro-geodetic Camera System (ACSYS) was developed in Turkey in 2015. The system components include a telescope, a Charged Coupled Device (CCD), two tiltmeters with the accuracy of 0.01 milliradians, a focuser, a single frequency GPS receiver and a substructure. The first version of the ACSYS is capable of determining astronomical coordinates with an accuracy of 0.2-0.3 arc sec, yet it has some limitations in observation duration. Because of the semi-automated mechanical design, leveling the system towards zenith was a time-consuming process. Since the beginning of 2016, the ACSYS has been modernized through the upgrade of the system with new technological components, hardware and software which is supported by The Scientific and Research Council of Turkey. Upgrade process includes the installation of a high-resolution tiltmeter with an accuracy of 1 nano-radians, implementation of a temperature compensating focuser and fully automatized substructure system. The components of the system are controlled by specially designed and integrated software. In the scope of the modernization studies, the project team has also been working on a unified real-time processing and control software for the ACSYS.v2. This study introduces the

Development of a System for Absolute Quantum Efficiency Determination of Hybrid Photo Diodes

CERN Document Server

Hammarstedt, P

2001-01-01

At CERN, the European Laboratory for Particle Physics, a new particle accelerator, the Large Hadron Collider (LHC), is under development. The detectors at LHC require development of highly sophisticated technologies, including Hybrid Photo Diodes (HPD) for high efficiency, high resolution single photon detection with a large area coverage. During the HPD development phase, one of the crucial parameters in the optimization of the photocathode creation process is the quantum efficiency. The aim of this Master Thesis has been to design and implement a system for high precision, high resolution quantum efficiency determination over a large, 200-700 nm photon wavelength range. Commercially available components have been obtained, an optomechanical system has been designed and built, and all the necessary data acquisition, control and analysis software has been implemented. The relative precision of the measurement system has been determined to 2%, with additional possible systematic errors less than 2%. Various qu...

Distinguishing signatures of determinism and stochasticity in spiking complex systems

Science.gov (United States)

Aragoneses, Andrés; Rubido, Nicolás; Tiana-Alsina, Jordi; Torrent, M. C.; Masoller, Cristina

2013-01-01

We describe a method to infer signatures of determinism and stochasticity in the sequence of apparently random intensity dropouts emitted by a semiconductor laser with optical feedback. The method uses ordinal time-series analysis to classify experimental data of inter-dropout-intervals (IDIs) in two categories that display statistically significant different features. Despite the apparent randomness of the dropout events, one IDI category is consistent with waiting times in a resting state until noise triggers a dropout, and the other is consistent with dropouts occurring during the return to the resting state, which have a clear deterministic component. The method we describe can be a powerful tool for inferring signatures of determinism in the dynamics of complex systems in noisy environments, at an event-level description of their dynamics.

Multiscale geometric modeling of macromolecules I: Cartesian representation

Science.gov (United States)

Xia, Kelin; Feng, Xin; Chen, Zhan; Tong, Yiying; Wei, Guo-Wei

2014-01-01

This paper focuses on the geometric modeling and computational algorithm development of biomolecular structures from two data sources: Protein Data Bank (PDB) and Electron Microscopy Data Bank (EMDB) in the Eulerian (or Cartesian) representation. Molecular surface (MS) contains non-smooth geometric singularities, such as cusps, tips and self-intersecting facets, which often lead to computational instabilities in molecular simulations, and violate the physical principle of surface free energy minimization. Variational multiscale surface definitions are proposed based on geometric flows and solvation analysis of biomolecular systems. Our approach leads to geometric and potential driven Laplace-Beltrami flows for biomolecular surface evolution and formation. The resulting surfaces are free of geometric singularities and minimize the total free energy of the biomolecular system. High order partial differential equation (PDE)-based nonlinear filters are employed for EMDB data processing. We show the efficacy of this approach in feature-preserving noise reduction. After the construction of protein multiresolution surfaces, we explore the analysis and characterization of surface morphology by using a variety of curvature definitions. Apart from the classical Gaussian curvature and mean curvature, maximum curvature, minimum curvature, shape index, and curvedness are also applied to macromolecular surface analysis for the first time. Our curvature analysis is uniquely coupled to the analysis of electrostatic surface potential, which is a by-product of our variational multiscale solvation models. As an expository investigation, we particularly emphasize the numerical algorithms and computational protocols for practical applications of the above multiscale geometric models. Such information may otherwise be scattered over the vast literature on this topic. Based on the curvature and electrostatic analysis from our multiresolution surfaces, we introduce a new concept, the

Multiscale geometric modeling of macromolecules I: Cartesian representation

Energy Technology Data Exchange (ETDEWEB)

Xia, Kelin [Department of Mathematics, Michigan State University, MI 48824 (United States); Feng, Xin [Department of Computer Science and Engineering, Michigan State University, MI 48824 (United States); Chen, Zhan [Department of Mathematics, Michigan State University, MI 48824 (United States); Tong, Yiying [Department of Computer Science and Engineering, Michigan State University, MI 48824 (United States); Wei, Guo-Wei, E-mail: wei@math.msu.edu [Department of Mathematics, Michigan State University, MI 48824 (United States); Department of Biochemistry and Molecular Biology, Michigan State University, MI 48824 (United States)

2014-01-15

This paper focuses on the geometric modeling and computational algorithm development of biomolecular structures from two data sources: Protein Data Bank (PDB) and Electron Microscopy Data Bank (EMDB) in the Eulerian (or Cartesian) representation. Molecular surface (MS) contains non-smooth geometric singularities, such as cusps, tips and self-intersecting facets, which often lead to computational instabilities in molecular simulations, and violate the physical principle of surface free energy minimization. Variational multiscale surface definitions are proposed based on geometric flows and solvation analysis of biomolecular systems. Our approach leads to geometric and potential driven Laplace–Beltrami flows for biomolecular surface evolution and formation. The resulting surfaces are free of geometric singularities and minimize the total free energy of the biomolecular system. High order partial differential equation (PDE)-based nonlinear filters are employed for EMDB data processing. We show the efficacy of this approach in feature-preserving noise reduction. After the construction of protein multiresolution surfaces, we explore the analysis and characterization of surface morphology by using a variety of curvature definitions. Apart from the classical Gaussian curvature and mean curvature, maximum curvature, minimum curvature, shape index, and curvedness are also applied to macromolecular surface analysis for the first time. Our curvature analysis is uniquely coupled to the analysis of electrostatic surface potential, which is a by-product of our variational multiscale solvation models. As an expository investigation, we particularly emphasize the numerical algorithms and computational protocols for practical applications of the above multiscale geometric models. Such information may otherwise be scattered over the vast literature on this topic. Based on the curvature and electrostatic analysis from our multiresolution surfaces, we introduce a new concept, the

An automatic system for acidity determination based on sequential injection titration and the monosegmented flow approach.

Science.gov (United States)

Kozak, Joanna; Wójtowicz, Marzena; Gawenda, Nadzieja; Kościelniak, Paweł

2011-06-15

An automatic sequential injection system, combining monosegmented flow analysis, sequential injection analysis and sequential injection titration is proposed for acidity determination. The system enables controllable sample dilution and generation of standards of required concentration in a monosegmented sequential injection manner, sequential injection titration of the prepared solutions, data collecting, and handling. It has been tested on spectrophotometric determination of acetic, citric and phosphoric acids with sodium hydroxide used as a titrant and phenolphthalein or thymolphthalein (in the case of phosphoric acid determination) as indicators. Accuracy better than |4.4|% (RE) and repeatability better than 2.9% (RSD) have been obtained. It has been applied to the determination of total acidity in vinegars and various soft drinks. The system provides low sample (less than 0.3 mL) consumption. On average, analysis of a sample takes several minutes. Copyright © 2011 Elsevier B.V. All rights reserved.

Growth factor and proteinase profile of Vivostat® platelet-rich fibrin linked to tissue repair.

Science.gov (United States)

Agren, M S; Rasmussen, K; Pakkenberg, B; Jørgensen, B

2014-07-01

Autologous platelet-rich fibrin (PRF(®)) is prepared by the automatic Vivostat(®) system. Conflicting results with Vivostat PRF in acute wound healing prompted us to examine its cellular and biomolecular composition. Specifically, platelets, selected growth factors and matrix metalloproteinase (MMP)-9 were quantified using novel analytical methods. Ten healthy non-thrombocytopenic volunteers donated blood for generation of intermediate fibrin-I and final PRF. Anticoagulated whole blood and serum procured in parallel served as baseline controls. Leucocyte, erythrocyte and platelet counts in whole blood and fibrin-I were determined by automated haematology analyser. Platelet concentration in PRF was quantified manually by stereologic analysis of Giemsa-stained tissue sections, and the total content of five growth factors and MMP-9 by enzyme-linked immunosorbent assays. The number of leucocytes and erythrocytes was reduced (P platelets increased (P fibrin-I versus whole blood. PRF contained 982 ± 206 × 10(9) platelets/l representing 3·9-fold (P platelet-derived growth factor (PDGF)-AB [2·5-fold, P PDGF-BB [1·6-fold, P vascular endothelial growth factor > basic fibroblast growth factor [75-fold, P platelet enrichment and biomolecular constituents may guide clinicians in their optimal use of Vivostat PRF for tissue regenerative applications. © 2013 International Society of Blood Transfusion.

Heuristic Optimization Techniques for Determining Optimal Reserve Structure of Power Generating Systems

DEFF Research Database (Denmark)

Ding, Yi; Goel, Lalit; Wang, Peng

2012-01-01

cost of the system will also increase. The reserve structure of a MSS should be determined based on striking a balance between the required reliability and the reserve cost. The objective of reserve management for a MSS is to schedule the reserve at the minimum system reserve cost while maintaining......Electric power generating systems are typical examples of multi-state systems (MSS). Sufficient reserve is critically important for maintaining generating system reliabilities. The reliability of a system can be increased by increasing the reserve capacity, noting that at the same time the reserve...... the required level of supply reliability to its customers. In previous research, Genetic Algorithm (GA) has been used to solve most reliability optimization problems. However, the GA is not very computationally efficient in some cases. In this chapter a new heuristic optimization technique—the particle swarm...

A new detection system for extremely small vertically mounted cantilevers

International Nuclear Information System (INIS)

Antognozzi, M; Ulcinas, A; Picco, L; Simpson, S H; Miles, M J; Heard, P J; Szczelkun, M D; Brenner, B

2008-01-01

Detection techniques currently used in scanning force microscopy impose limitations on the geometrical dimensions of the probes and, as a consequence, on their force sensitivity and temporal response. A new technique, based on scattered evanescent electromagnetic waves (SEW), is presented here that can detect the displacement of the extreme end of a vertically mounted cantilever. The resolution of this method is tested using different cantilever sizes and a theoretical model is developed to maximize the detection sensitivity. The applications presented here clearly show that the SEW detection system enables the use of force sensors with sub-micron size, opening new possibilities in the investigation of biomolecular systems and high speed imaging. Two types of cantilevers were successfully tested: a high force sensitivity lever with a spring constant of 0.17 pN nm -1 and a resonant frequency of 32 kHz; and a high speed lever with a spring constant of 50 pN nm -1 and a resonant frequency of 1.8 MHz. Both these force sensors were fabricated by modifying commercial microcantilevers in a focused ion beam system. It is important to emphasize that these modified cantilevers could not be detected by the conventional optical detection system used in commercial atomic force microscopes

A Teaching and Learning Sequence about the Interplay of Chance and Determinism in Nonlinear Systems

Science.gov (United States)

Stavrou, D.; Duit, R.; Komorek, M.

2008-01-01

A teaching and learning sequence aimed at introducing upper secondary school students to the interplay between chance and determinism in nonlinear systems is presented. Three experiments concerning nonlinear systems (deterministic chaos, self-organization and fractals) and one experiment concerning linear systems are introduced. Thirty upper…

Noncovalent synthesis of protein dendrimers

NARCIS (Netherlands)

Lempens, E.H.M.; Baal, van I.; Dongen, van J.L.J.; Hackeng, T.M.; Merkx, M.; Meijer, E.W.

2009-01-01

The covalent synthesis of complex biomolecular systems such as multivalent protein dendrimers often proceeds with low efficiency, thereby making alternative strategies based on noncovalent chemistry of high interest. Here, the synthesis of protein dendrimers using a strong but noncovalent

Thunderstorm Algorithm for Determining Unit Commitment in Power System Operation

Directory of Open Access Journals (Sweden)

Arif Nur Afandi

2016-12-01

Full Text Available Solving the unit commitment problem is an important task in power system operation for deciding a balanced power production between various types of generating units under technical constraints and environmental limitations. This paper presents a new intelligent computation method, called the Thunderstorm Algorithm (TA, for searching the optimal solution of the integrated economic and emission dispatch (IEED problem as the operational assessment for determining unit commitment. A simulation using the IEEE-62 bus system showed that TA has smooth convergence and is applicable for solving the IEED problem. The IEED’s solution is associated with the total fuel consumption and pollutant emission. The proposed TA method seems to be a viable new approach for finding the optimal solution of the IEED problem.

Ion-molecular equilibria and activity determination in the RbF-ZrF4 system

International Nuclear Information System (INIS)

Skokan, E.V.; Nikitin, M.I.; Sorokin, I.D.; Korenev, Yu.M.; Sidorov, L.N.

1983-01-01

Activity of zirconium tetrofluoride in 100-33.3 mol % ZrF 4 concentration range was determined during isothermal evaporation of samples of different initial composition of RbF-ZrF 4 system, using ion-molecular equilibrium method. It became possible, using the exchange ion-molecular reactions to determine ZrF 4 activity approximately 10 -10 in the region of state diagram of RbF-ZrF 4 system, adjoining to rubidium fluoride. The comparative analysis of results, obtained by the methods of isothermal evaporation, ion-molecular equilibria is given; the advantages and restrictions of ion-molecular equilibrium method are presented

Biomolecular tracing using long-lived isotopes

International Nuclear Information System (INIS)

Vogel, J.S.; Turteltaub, K.W.; Frantz, C.E.; Keating, G.; Felton, J.S.; Southon, J.R.; Roberts, M.R.; Gledhill, B.L.

1992-01-01

Accelerator mass spectrometry (AMS) was developed over the past 15 years as an essential tool for detecting long-lived, cosmogenic radio-isotopes in the earth and space sciences. We apply this technology to the measurement of chemical kinetics, primarily in biomedical systems, which had heretofore employed short-lived isotopes and/or long counting times to quantify radio-isotopic labels. AMS provides detection efficiencies of ∼ 1%, 10 3 to 10 6 better than decay-counting. Long-lived isotopes are used and detected with AMS at concentrations which reduce sample size, chemical dose, radiation safety hazards and radiolysis. We measure 3 H, 7,1O Be, 14 C, 26 Al, 36 CI, 41 Ca and 129 I, but most of our current program uses 14 C. Initial experiments involved research on the genotoxicity of mutagens in cooked foods and reversible binding of compounds to antibodies. Through collaborations, we apply AMS detection to research in carcinogenesis, pharmacokinetics of toxins, elemental metabolism, distribution of topical medications and nutrition

Profitability of Western European banking systems: panel evidence on structural and cyclical determinants

OpenAIRE

Beckmann, Rainer

2007-01-01

This paper analyses structural and cyclical determinants of banking profitability in 16 Western European countries. We find that financial structure matters, particularly through the beneficial effect of the capital market orientation in the respective national financial system. Furthermore, higher diversification regarding banks' income sources shows a positive effect. The industry concentration of national banking systems, though, does not significantly affect aggregate profitability. Busin...

A concept of a component based system to determine pot-plant shelf-life

DEFF Research Database (Denmark)

Körner, Oliver; Skou, Anne-Marie Thonning; Aaslyng, Jesper Peter Mazanti

2006-01-01

to calculate the expected keeping quality, or it will be able to apply the system as decision support during plant cultivation. In the latter case, the model-based system can be implemented in a greenhouse climate computer. The concept contains information on climate control strategies, controlled stress......, the keeping quality of a plant after removal from the greenhouse could be estimated. A concept of a system that describes a model based knowledge system aiming at determination of the last selling date for pot plants is presented. The core of the conceptual system is a tool that can either be used......, diseases, nutrient management and substrates....

Optimum capacity determination of stand-alone hybrid generation system considering cost and reliability

International Nuclear Information System (INIS)

Chen, Hung-Cheng

2013-01-01

Highlights: ► This paper presents a methodology for the installation capacity optimization. ► Hybrid generation system is optimized by application of adaptive genetic algorithm. ► A cost investigation is made under various conditions and component characteristics. ► The optimization scheme is validated to meet the annual power load demand. -- Abstract: The aim of this work is to present an optimization methodology for the installation capacity of a stand-alone hybrid generation system, taking into consideration the cost and reliability. Firstly, on the basis of derived steady state models of a wind generator (WG), a photovoltaic array (PV), a battery and an inverter, the hybrid generation system is modeled for the purpose of capacity optimization. Secondly, the power system is analyzed for determining both the system structure and the operation control strategy. Thirdly, according to hourly weather database of wind speed, temperature and solar irradiation, annual power generation capacity is estimated for the system match design in order that an annual power load demand can be met. The capacity determination of a hybrid generation system becomes complicated as a result of the uncertainty in the renewable energy together with load demand and the nonlinearity of system components. Aimed at the power system reliability and the cost minimization, the capacity of a hybrid generation system is optimized by application of an adaptive genetic algorithm (AGA) to individual power generation units. A total cost investigation is made under various conditions, such as wind generator power curves, battery discharge depth and the loss of load probability (LOLP). At the end of this work, the capacity of a hybrid generation system is optimized at two installation sites, namely the offshore Orchid Island and Wuchi in Taiwan. The optimization scheme is validated to optimize power capacities of a photovoltaic array, a battery and a wind turbine generator with a relative

Sensitivity and Resolution Enhanced Solid-State NMR for Paramagnetic Systems and Biomolecules under Very Fast Magic Angle Spinning

KAUST Repository

Parthasarathy, Sudhakar

2013-09-17

Recent research in fast magic angle spinning (MAS) methods has drastically improved the resolution and sensitivity of NMR spectroscopy of biomolecules and materials in solids. In this Account, we summarize recent and ongoing developments in this area by presenting (13)C and (1)H solid-state NMR (SSNMR) studies on paramagnetic systems and biomolecules under fast MAS from our laboratories. First, we describe how very fast MAS (VFMAS) at the spinning speed of at least 20 kHz allows us to overcome major difficulties in (1)H and (13)C high-resolution SSNMR of paramagnetic systems. As a result, we can enhance both sensitivity and resolution by up to a few orders of magnitude. Using fast recycling (∼ms/scan) with short (1)H T1 values, we can perform (1)H SSNMR microanalysis of paramagnetic systems on the microgram scale with greatly improved sensitivity over that observed for diamagnetic systems. Second, we discuss how VFMAS at a spinning speed greater than ∼40 kHz can enhance the sensitivity and resolution of (13)C biomolecular SSNMR measurements. Low-power (1)H decoupling schemes under VFMAS offer excellent spectral resolution for (13)C SSNMR by nominal (1)H RF irradiation at ∼10 kHz. By combining the VFMAS approach with enhanced (1)H T1 relaxation by paramagnetic doping, we can achieve extremely fast recycling in modern biomolecular SSNMR experiments. Experiments with (13)C-labeled ubiquitin doped with 10 mM Cu-EDTA demonstrate how effectively this new approach, called paramagnetic assisted condensed data collection (PACC), enhances the sensitivity. Lastly, we examine (13)C SSNMR measurements for biomolecules under faster MAS at a higher field. Our preliminary (13)C SSNMR data of Aβ amyloid fibrils and GB1 microcrystals acquired at (1)H NMR frequencies of 750-800 MHz suggest that the combined use of the PACC approach and ultrahigh fields could allow for routine multidimensional SSNMR analyses of proteins at the 50-200 nmol level. Also, we briefly discuss the

Covering all the bases : Coarse-grained model design and application for nucleic acids

NARCIS (Netherlands)

Uusitalo, Jaakko Juhani

2016-01-01

Nucleic acids play a crucial role in the storage, transportation and expression of our genetic information. They have also become an interesting tool for many applications in nanotechnology. Studying biomolecular systems containing nucleic acids using experimental and imaging techniques has its

Force and Stress along Simulated Dissociation Pathways of Cucurbituril-Guest Systems.

Science.gov (United States)

Velez-Vega, Camilo; Gilson, Michael K

2012-03-13

The field of host-guest chemistry provides computationally tractable yet informative model systems for biomolecular recognition. We applied molecular dynamics simulations to study the forces and mechanical stresses associated with forced dissociation of aqueous cucurbituril-guest complexes with high binding affinities. First, the unbinding transitions were modeled with constant velocity pulling (steered dynamics) and a soft spring constant, to model atomic force microscopy (AFM) experiments. The computed length-force profiles yield rupture forces in good agreement with available measurements. We also used steered dynamics with high spring constants to generate paths characterized by a tight control over the specified pulling distance; these paths were then equilibrated via umbrella sampling simulations and used to compute time-averaged mechanical stresses along the dissociation pathways. The stress calculations proved to be informative regarding the key interactions determining the length-force profiles and rupture forces. In particular, the unbinding transition of one complex is found to be a stepwise process, which is initially dominated by electrostatic interactions between the guest's ammoniums and the host's carbonyl groups, and subsequently limited by the extraction of the guest's bulky bicyclooctane moiety; the latter step requires some bond stretching at the cucurbituril's extraction portal. Conversely, the dissociation of a second complex with a more slender guest is mainly driven by successive electrostatic interactions between the different guest's ammoniums and the host's carbonyl groups. The calculations also provide information on the origins of thermodynamic irreversibilities in these forced dissociation processes.

A semi-physical simulation platform of attitude determination and control system for satellite

Directory of Open Access Journals (Sweden)

Yuanjin Yu

2016-05-01

Full Text Available A semi-physical simulation platform for attitude determination and control system is proposed to verify the attitude estimator and controller on ground. A simulation target, a host PC, many attitude sensors, and actuators compose the simulation platform. The simulation target is composed of a central processing unit board with VxWorks operating system and many input/output boards connected via Compact Peripheral Component Interconnect bus. The executable programs in target are automatically generated from the simulation models in Simulink based on Real-Time Workshop of MATLAB. A three-axes gyroscope, a three-axes magnetometer, a sun sensor, a star tracer, three flywheels, and a Global Positioning System receiver are connected to the simulation target, which formulates the attitude control cycle of a satellite. The simulation models of the attitude determination and control system are described in detail. Finally, the semi-physical simulation platform is used to demonstrate the availability and rationality of the control scheme of a micro-satellite. Comparing the results between the numerical simulation in Simulink and the semi-physical simulation, the semi-physical simulation platform is available and the control scheme successfully achieves three-axes stabilization.

[How can the coding quality in the DRG system be determined?].

Science.gov (United States)

Kahlmeyer, A; Volkmer, B

2014-01-01

The permanent adjustments ​​since 2003 to the G-DRG system have made the system even less understandable, so that many users have the feeling of feeding data into a black box which gives them a result without them being able to actively use the system itself. While chief physicians, senior physicians, and nursing managers are responsible to management for the results of the billing, they are in most cases not involved in the steps of DRG coding and billing. From this situation, a common question arises: "How well does my department code?" This uncertainty is exploited by many commercial vendors, who offer a wide variety of approaches for DRG optimization. The goal of this work is to provide advice as to how coding quality can be determined.

Crop Evaluation System Optimization: Attribute Weights Determination Based on Rough Sets Theory

Directory of Open Access Journals (Sweden)

Ruihong Wang

2017-01-01

Full Text Available The present study is mainly a continuation of our previous study, which is about a crop evaluation system development that is based on grey relational analysis. In that system, the attribute weight determination affects the evaluation result directly. Attribute weight is usually ascertained by decision-makers experience knowledge. In this paper, we utilize rough sets theory to calculate attribute significance and then combine it with weight given by decision-maker. This method is a comprehensive consideration of subjective experience knowledge and objective situation; thus it can acquire much more ideal results. Finally, based on this method, we improve the system based on ASP.NET technology.

System and method for clock synchronization and position determination using entangled photon pairs

Science.gov (United States)

Shih, Yanhua (Inventor)

2010-01-01

A system and method for clock synchronization and position determination using entangled photon pairs is provided. The present invention relies on the measurement of the second order correlation function of entangled states. Photons from an entangled photon source travel one-way to the clocks to be synchronized. By analyzing photon registration time histories generated at each clock location, the entangled states allow for high accuracy clock synchronization as well as high accuracy position determination.

Determination of tributyl phosphate (TBP) by precision densimetry : TBP-varsol-HNO3 system

International Nuclear Information System (INIS)

Matsuda, H.T.; Araujo, B.F. de; Araujo, J.A. de

1980-01-01

A simple and rapid method for TBP direct determination is presented, based on precision densimetry, aiming to control solvent concentration in the TBP-Varsol system during the reprocessing of irradiated uranium. The method comprises the determination of the density of liquids or gases by electronic measurement of the variation in the frequency (f) or period (T = 1/f) of a glass oscillator containing the liquid or the gas. (C.L.B.) [pt

Human error considerations and annunciator effects in determining optimal test intervals for periodically inspected standby systems

International Nuclear Information System (INIS)

McWilliams, T.P.; Martz, H.F.

1981-01-01

This paper incorporates the effects of four types of human error in a model for determining the optimal time between periodic inspections which maximizes the steady state availability for standby safety systems. Such safety systems are characteristic of nuclear power plant operations. The system is modeled by means of an infinite state-space Markov chain. Purpose of the paper is to demonstrate techniques for computing steady-state availability A and the optimal periodic inspection interval tau* for the system. The model can be used to investigate the effects of human error probabilities on optimal availability, study the benefits of annunciating the standby-system, and to determine optimal inspection intervals. Several examples which are representative of nuclear power plant applications are presented

Congestion management by determining optimal location of TCSC in deregulated power systems

International Nuclear Information System (INIS)

Besharat, Hadi; Taher, Seyed Abbas

2008-01-01

In a deregulated electricity market, it may always not be possible to dispatch all of the contracted power transactions due to congestion of the transmission corridors. The ongoing power system restructuring requires an opening of unused potentials of transmission system due to environmental, right-of-way and cost problems which are major hurdles for power transmission network expansion. Flexible AC transmission systems (FACTSs) devices can be an alternative to reduce the flows in heavily loaded lines, resulting in an increased loadability, low system loss, improved stability of the network, reduced cost of production and fulfilled contractual requirement by controlling the power flows in the network. A method to determine the optimal location of thyristor controlled series compensators (TCSCs) has been suggested in this paper based on real power performance index and reduction of total system VAR power losses. (author)

A Method for Determining Pseudo-measurement State Values for Topology Observability of State Estimation in Power Systems

Science.gov (United States)

Urano, Shoichi; Mori, Hiroyuki

This paper proposes a new technique for determining of state values in power systems. Recently, it is useful for carrying out state estimation with data of PMU (Phasor Measurement Unit). The authors have developed a method for determining state values with artificial neural network (ANN) considering topology observability in power systems. ANN has advantage to approximate nonlinear functions with high precision. The method evaluates pseudo-measurement state values of the data which are lost in power systems. The method is successfully applied to the IEEE 14-bus system.

System to determine present elements in oily samples

International Nuclear Information System (INIS)

Mendoza G, Y.

2004-11-01

In the Chemistry Department of the National Institute of Nuclear Investigations of Mexico, dedicated to analyze samples of oleaginous material and of another origin, to determine the elements of the periodic table present in the samples, through the Neutron activation analysis technique (NAA). This technique has been developed to determine majority elements in any solid, aqueous, industrial and environmental sample, which consists basically on to irradiate a sample with neutrons coming from the TRIGA Mark III reactor and to carry out the analysis to obtain those gamma spectra that it emits, for finally to process the information, the quantification of the analysis it is carried out in a manual way, which requires to carry out a great quantity of calculations. The main objective of this project is the development of a software that allows to carry out the quantitative analysis of the NAA for the multielemental determination of samples in an automatic way. To fulfill the objective of this project it has been divided in four chapters: In the first chapter it is shortly presented the history on radioactivity and basic concepts that will allow us penetrate better to this work. In the second chapter the NAA is explained which is used in the sample analysis, the description of the process to be carried out, its are mentioned the characteristics of the used devices and an example of the process is illustrated. In the third chapter it is described the development of the algorithm and the selection of the programming language. The fourth chapter it is shown the structure of the system, the general form of operation, the execution of processes and the obtention of results. Later on the launched results are presented in the development of the present project. (Author)

Portable LIBS system for determining the composition of multilayer structures on objects of cultural value

International Nuclear Information System (INIS)

Moreira Osorio, Lesther; Ponce Cabrera, Luis V; Arronte Garcia, Miguel A; Flores Reyes, Teresa; Ravelo, Ivette

2011-01-01

This study presents the use of a portable Laser Induced Breakdown Spectroscopy (LIBS) prototype for determining the elemental composition of a metal jug. The system includes emission from a multiuse Q-switched Nd:YAG laser. By sampling at different points, the surface composition is determined. Furthermore, the presence of two layers of Pb and Cu and their thicknesses are determined through in-depth analysis.

An Improved Setpoint Determination Methodology for the Plant Protection System Considering Beyond Design Basis Events

International Nuclear Information System (INIS)

Lee, C.J.; Baik, K.I.; Baek, S.M.; Park, K.-M.; Lee, S.J.

2013-06-01

According to the nuclear regulations and industry standards, the trip setpoint and allowable value for the plant protection system have been determined by considering design basis events. In order to improve the safety of a nuclear power plant, an attempt has been made to develop an improved setpoint determination methodology for the plant protection system trip parameter considering not only a design basis event but also a beyond design basis event. The results of a quantitative evaluation performed for the Advanced Power Reactor 1400 nuclear power plant in Korea are presented herein. The results confirmed that the proposed methodology is able to improve the nuclear power plant's safety by determining more reasonable setpoints that can cover beyond design basis events. (authors)

Exploiting an automated microfluidic hydrodynamic sequential injection system for determination of phosphate.

Science.gov (United States)

Khongpet, Wanpen; Pencharee, Somkid; Puangpila, Chanida; Kradtap Hartwell, Supaporn; Lapanantnoppakhun, Somchai; Jakmunee, Jaroon

2018-01-15

A microfluidic hydrodynamic sequential injection (μHSI) spectrophotometric system was designed and fabricated. The system was built by laser engraving a manifold pattern on an acrylic block and sealing with another flat acrylic plate to form a microfluidic channel platform. The platform was incorporated with small solenoid valves to obtain a portable setup for programmable control of the liquid flow into the channel according to the HSI principle. The system was demonstrated for the determination of phosphate using a molybdenum blue method. An ascorbic acid, standard or sample, and acidic molybdate solutions were sequentially aspirated to fill the channel forming a stack zone before flowing to the detector. Under the optimum condition, a linear calibration graph in the range of 0.1-6mg P L -1 was obtained. The detection limit was 0.1mgL -1 . The system is compact (5.0mm thick, 80mm wide × 140mm long), durable, portable, cost-effective, and consumes little amount of chemicals (83μL each of molybdate and ascorbic acid, 133μL of the sample solution and 1.7mL of water carrier/run). It was applied for the determination of phosphate content in extracted soil samples. The percent recoveries of the analysis were obtained in the range of 91.2-107.3. The results obtained agreed well with those of the batch spectrophotometric method. Copyright © 2017 Elsevier B.V. All rights reserved.

State determination for composite systems of two spatial qubits

International Nuclear Information System (INIS)

Lima, G; Torres-Ruiz, F A; Neves, L; Delgado, A; Saavedra, C; Padua, S

2007-01-01

In a recent letter [Phys. Rev. Lett. 94, 100501 (2005)], we presented a scheme for generating pure entangled states of spatial qudits using transverse correlations of parametric down-converted photons. Here we show how the modication of this scheme can be used to generate mixed states and we investigate the state determination for composite systems of two spatial qubits, motivated by the fact that quantum information protocols may be easier to be implemented for this case. By means of local operations on the twin photons we were able to perform the quantum tomography process to reconstruct the density matrix of a mixed state of two spatial qubits

A Method to Determine Oscillation Emergence Bifurcation in Time-Delayed LTI System with Single Lag

Directory of Open Access Journals (Sweden)

Yu Xiaodan

2014-01-01

Full Text Available One type of bifurcation named oscillation emergence bifurcation (OEB found in time-delayed linear time invariant (abbr. LTI systems is fully studied. The definition of OEB is initially put forward according to the eigenvalue variation. It is revealed that a real eigenvalue splits into a pair of conjugated complex eigenvalues when an OEB occurs, which means the number of the system eigenvalues will increase by one and a new oscillation mode will emerge. Next, a method to determine OEB bifurcation in the time-delayed LTI system with single lag is developed based on Lambert W function. A one-dimensional (1-dim time-delayed system is firstly employed to explain the mechanism of OEB bifurcation. Then, methods to determine the OEB bifurcation in 1-dim, 2-dim, and high-dimension time-delayed LTI systems are derived. Finally, simulation results validate the correctness and effectiveness of the presented method. Since OEB bifurcation occurs with a new oscillation mode emerging, work of this paper is useful to explore the complex phenomena and the stability of time-delayed dynamic systems.

Unconstrained Enhanced Sampling for Free Energy Calculations of Biomolecules: A Review

Science.gov (United States)

Miao, Yinglong; McCammon, J. Andrew

2016-01-01

Free energy calculations are central to understanding the structure, dynamics and function of biomolecules. Yet insufficient sampling of biomolecular configurations is often regarded as one of the main sources of error. Many enhanced sampling techniques have been developed to address this issue. Notably, enhanced sampling methods based on biasing collective variables (CVs), including the widely used umbrella sampling, adaptive biasing force and metadynamics, have been discussed in a recent excellent review (Abrams and Bussi, Entropy, 2014). Here, we aim to review enhanced sampling methods that do not require predefined system-dependent CVs for biomolecular simulations and as such do not suffer from the hidden energy barrier problem as encountered in the CV-biasing methods. These methods include, but are not limited to, replica exchange/parallel tempering, self-guided molecular/Langevin dynamics, essential energy space random walk and accelerated molecular dynamics. While it is overwhelming to describe all details of each method, we provide a summary of the methods along with the applications and offer our perspectives. We conclude with challenges and prospects of the unconstrained enhanced sampling methods for accurate biomolecular free energy calculations. PMID:27453631

A Study on the Determination of Power Supply Class for HVAC System in KJRR

International Nuclear Information System (INIS)

Kim, Hagtae; Kim, Minjin; Suh, Yong-Suk; Kim, Jun-Yeon; Chae, Hee-Taek

2016-01-01

The purpose of this paper is to propose an appropriate electrical class, power supply class, and operation logic for the major equipment of the HVAC system such as a Confinement Isolation Damper (CID), Fission Molybdenum Isolation Damper (FID), Air Handling Unit (AHU), Air Cleaning Unit (ACU), and Contaminated Air Purification System (CAPS) in light of their functional requirements and importance. The classification for the overall HVAC system of the KJRR is a safety class NNS, Non-Seismic category, quality class S, and electrical class Non-1E. Exceptionally, the CID and FID are safety class 3, seismic category I, and quality class Q. The electrical class for the major equipment of the HVAC system should be determined considering the operation concept during Loss of Normal Electric Power (LOEP) regardless of the safety class. In this paper, the electrical and power supply class is determined and the operation logic is proposed for the major equipment of the HVAC system for the KJRR such as the CID, FID, CAPS, ACU, and AHU. The electrical class Non-1E is determined to implement a fail closed for the enhancement of safety. The power supply class is based on the functional requirements of each equipment. The CID, FID, CAPS, and ACU are Class III, but the AHU is Class IV by reflecting the importance and electrical load. After the recovery of the power supply, there is a difference in the operation concept for the HVAC system between the reactor building and fission molybdenum production building depending on the operator's residence time. The CID and CAPS are operated manually through procedures for checking the accident status, and the FID and ACU are operated automatically without special procedures

A Study on the Determination of Power Supply Class for HVAC System in KJRR

Energy Technology Data Exchange (ETDEWEB)

Kim, Hagtae; Kim, Minjin; Suh, Yong-Suk; Kim, Jun-Yeon; Chae, Hee-Taek [KAERI, Daejeon (Korea, Republic of)

2016-05-15

The purpose of this paper is to propose an appropriate electrical class, power supply class, and operation logic for the major equipment of the HVAC system such as a Confinement Isolation Damper (CID), Fission Molybdenum Isolation Damper (FID), Air Handling Unit (AHU), Air Cleaning Unit (ACU), and Contaminated Air Purification System (CAPS) in light of their functional requirements and importance. The classification for the overall HVAC system of the KJRR is a safety class NNS, Non-Seismic category, quality class S, and electrical class Non-1E. Exceptionally, the CID and FID are safety class 3, seismic category I, and quality class Q. The electrical class for the major equipment of the HVAC system should be determined considering the operation concept during Loss of Normal Electric Power (LOEP) regardless of the safety class. In this paper, the electrical and power supply class is determined and the operation logic is proposed for the major equipment of the HVAC system for the KJRR such as the CID, FID, CAPS, ACU, and AHU. The electrical class Non-1E is determined to implement a fail closed for the enhancement of safety. The power supply class is based on the functional requirements of each equipment. The CID, FID, CAPS, and ACU are Class III, but the AHU is Class IV by reflecting the importance and electrical load. After the recovery of the power supply, there is a difference in the operation concept for the HVAC system between the reactor building and fission molybdenum production building depending on the operator's residence time. The CID and CAPS are operated manually through procedures for checking the accident status, and the FID and ACU are operated automatically without special procedures.

ORGANISATIONAL DETERMINANTS INFLUENCING INFORMATION SYSTEMS REIMPLEMENTATION: SOME IMPLICATIONS TO THE DEVELOPING COUNTRIES

Directory of Open Access Journals (Sweden)

Sayyen Teoh

2010-01-01

Full Text Available This article presents an in-depth study of global Web-based Marketing Decision Support System reimplementation, in a British-based Fast Moving Consumer Goods (FMCG manufacturer. The paper shows that the success of a system implementation can still be marginal even if the organisation understands the key organisational determinants of success and has influence over them. The paper concludes with a discussion of how implementation planning, user need analysis and communication problems could be overcomed and also some implications to the companies in the developing nations.

Error analysis for determination of accuracy of an ultrasound navigation system for head and neck surgery.

Science.gov (United States)

Kozak, J; Krysztoforski, K; Kroll, T; Helbig, S; Helbig, M

2009-01-01

The use of conventional CT- or MRI-based navigation systems for head and neck surgery is unsatisfactory due to tissue shift. Moreover, changes occurring during surgical procedures cannot be visualized. To overcome these drawbacks, we developed a novel ultrasound-guided navigation system for head and neck surgery. A comprehensive error analysis was undertaken to determine the accuracy of this new system. The evaluation of the system accuracy was essentially based on the method of error definition for well-established fiducial marker registration methods (point-pair matching) as used in, for example, CT- or MRI-based navigation. This method was modified in accordance with the specific requirements of ultrasound-guided navigation. The Fiducial Localization Error (FLE), Fiducial Registration Error (FRE) and Target Registration Error (TRE) were determined. In our navigation system, the real error (the TRE actually measured) did not exceed a volume of 1.58 mm(3) with a probability of 0.9. A mean value of 0.8 mm (standard deviation: 0.25 mm) was found for the FRE. The quality of the coordinate tracking system (Polaris localizer) could be defined with an FLE of 0.4 +/- 0.11 mm (mean +/- standard deviation). The quality of the coordinates of the crosshairs of the phantom was determined with a deviation of 0.5 mm (standard deviation: 0.07 mm). The results demonstrate that our newly developed ultrasound-guided navigation system shows only very small system deviations and therefore provides very accurate data for practical applications.

Comparative study on novel test systems to determine disintegration time of orodispersible films.

Science.gov (United States)

Preis, Maren; Gronkowsky, Dorothee; Grytzan, Dominik; Breitkreutz, Jörg

2014-08-01

Orodispersible films (ODFs) are a promising innovative dosage form enabling drug administration without the need for water and minimizing danger of aspiration due to their fast disintegration in small amounts of liquid. This study focuses on the development of a disintegration test system for ODFs. Two systems were developed and investigated: one provides an electronic end-point, and the other shows a transferable setup of the existing disintegration tester for orodispersible tablets. Different ODF preparations were investigated to determine the suitability of the disintegration test systems. The use of different test media and the impact of different storage conditions of ODFs on their disintegration time were additionally investigated. The experiments showed acceptable reproducibility (low deviations within sample replicates due to a clear determination of the measurement end-point). High temperatures and high humidity affected some of the investigated ODFs, resulting in higher disintegration time or even no disintegration within the tested time period. The methods provided clear end-point detection and were applicable for different types of ODFs. By the modification of a conventional test system to enable application for films, a standard method could be presented to ensure uniformity in current quality control settings. © 2014 Royal Pharmaceutical Society.

Experimental model for neutron scattering in disordered systems: static structure factor determination of mode-softening

International Nuclear Information System (INIS)

Siegel, E.

1982-01-01

The generalized-disorder collective-boson mode-softening universality-principle (GDCBMSUP) for collective-boson mode dispersion in disordered systems (liquids, quantum liquids, glasses, powders, disordered magnets, plasmas...), a unified qualitative and semi-qualitative and semi-quantitative descriptive prescription for treating the properties of very differently disordered systems, is directly dependent upon a measurement (or calculation) of the static structure factor S(k) determined from a frequency average of the dynamic structure factor S(k,w), a multiple of the inelastic differential neutron scattering cross section d 2 sigma/dwdOMEGA. The prescription for this principle is given and, because of its universal applicability to disordered systems of any type with any type and/or degree of disorder, the neutron scattering determination of S(k) takes on renewed importance

Hybrid expert system implementation to determine core reload patterns

International Nuclear Information System (INIS)

Greek, K.J.; Robinson, A.H.

1989-01-01

Determining reactor reload fuel patterns is a computationally intensive problem solving process for which automation can be of significant benefit. Often much effort is expended in the search for an optimal loading. While any modern programming language could be used to automate solution, the specialized tools of artificial intelligence (AI) are the most efficient means of introducing the fuel management expert's knowledge into the search for an optimum reload pattern. Prior research in pressurized water reactor refueling strategies developed FORTRAN programs that automated an expert's basic knowledge to direct a search for an acceptable minimum peak power loading. The dissatisfaction with maintenance of compiled knowledge in FORTRAN programs has served as the motivation for the development of the SHUFFLE expert system. SHUFFLE is written in Smalltalk, an object-oriented programming language, and evaluates loadings as it generates them using a two-group, two-dimensional nodal power calculation compiled in a personal computer-based FORTRAN. This paper reviews the object-oriented representation developed to solve the core reload problem with an expert system tool and its operating prototype, SHUFFLE

Teaching and Learning the Interplay between Chance and Determinism in Nonlinear Systems

Science.gov (United States)

Stavrou, Dimitrios; Duit, Reinders

2014-01-01

That the interplay of random and deterministic processes may result in both the limited predictability of nonlinear systems and the formation of structures seems to be a most valuable general insight into the nature of science. This study investigates the possibility of teaching and learning the interplay of chance and determinism in nonlinear…

Determinants of the renin-angiotensin-aldosterone system in cirrhosis with special emphasis on the central blood volume

DEFF Research Database (Denmark)

Møller, Søren; Bendtsen, Flemming; Henriksen, Jens H

2006-01-01

OBJECTIVE: Several studies have shown activation of the renin-angiotensin-aldosterone system (RAAS) in cirrhosis. Although the activated RAAS may have several determinants, the system is often considered a surrogate marker of effective hypovolaemia. In this study we investigated the activity...... of the RAAS and its potential determinants with special focus on the central and arterial blood volume (CBV). MATERIAL AND METHODS: Eighty-nine patients (Child class A/B/C: 19/41/29) and 32 controls were included in the study. All were given a haemodynamic examination with measurement of determinants...

Biomolecular transport and separation in nanotubular networks.

Energy Technology Data Exchange (ETDEWEB)

Stachowiak, Jeanne C.; Stevens, Mark Jackson (Sandia National Laboratories, Albuquerque, NM); Robinson, David B.; Branda, Steven S.; Zendejas, Frank; Meagher, Robert J.; Sasaki, Darryl Yoshio; Bachand, George David (Sandia National Laboratories, Albuquerque, NM); Hayden, Carl C.; Sinha, Anupama; Abate, Elisa; Wang, Julia; Carroll-Portillo, Amanda (Sandia National Laboratories, Albuquerque, NM); Liu, Haiqing (Sandia National Laboratories, Albuquerque, NM)

2010-09-01

Cell membranes are dynamic substrates that achieve a diverse array of functions through multi-scale reconfigurations. We explore the morphological changes that occur upon protein interaction to model membrane systems that induce deformation of their planar structure to yield nanotube assemblies. In the two examples shown in this report we will describe the use of membrane adhesion and particle trajectory to form lipid nanotubes via mechanical stretching, and protein adsorption onto domains and the induction of membrane curvature through steric pressure. Through this work the relationship between membrane bending rigidity, protein affinity, and line tension of phase separated structures were examined and their relationship in biological membranes explored.

FY 1998 achievement report on the R and D for accelerating the basement arrangement of the biological resource information. Bioinformatics; 1998 nendo seibutsu shigen joho kiban seibi kasokuka kenkyu kaihatsu seika hokokusho. Bioinformatics

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-04-01

The paper described the FY 1998 results of the development of bioinformatics. All structure/sequence known proteins from all public databases were hierarchically classified systematically and according to similarities among sequences. Individual proteins in each classified group were added with explanatory notes of structure and physiological function. The mutually related information in metabolic system/signal transfer system was also included. The state of each residue position was classified into three states in terms of the solvent accessibility and three states in terms of the secondary structure. Parameter sets of occurrence frequency for each state of 20 kinds of amino acid were made. By these, it can be evaluated how much the arbitrary amino acid sequence is suitable for each structure in database. The data on the structure of low molecular-weight compounds are also incorporated so that the search for the related biomolecular system information becomes possible. The metabolic system/signal transfer system information was made database, the link was formed between each protein and each low molecular-weight compound, and the information on biomolecular networks was made searchable. A system to predict/support protein structure and function was developed. (NEDO)

Improvement of the superconducting magnetic levitation system for the determination of the magnetic flux quantum

International Nuclear Information System (INIS)

Endo, T.; Sakamoto, Y.; Shiota, F.; Nakayama, K.; Nezu, Y.; Kikuzawa, M.; Hara, K.

1989-01-01

The authors describe an improvement of the preliminary superconducting magnetic levitation system in progress for the absolute determination of the magnetic flux quantum. This improvement includes the development of the flux-up method to determine the flux in terms of the Josephson voltage. The improvement is essential for the determination of the magnetic flux quantum as well as of the coil current in terms of the Josephson voltage and quantized Hall resistance

Participation determinants in the DRG payment system of obstetrics and gynecology clinics in South Korea.

Science.gov (United States)

Song, Jung-Kook; Kim, Chang-yup

2010-03-01

The Diagnosis Related Group (DRG) payment system, which has been implemented in Korea since 1997, is based on voluntary participation. Hence, the positive impact of this system depends on the participation of physicians. This study examined the factors determining participation of Korean obstetrics & gynecology (OBGYN) clinics in the DRG-based payment system. The demographic information, practice-related variables of OBGYN clinics and participation information in the DRG-based payment system were acquired from the nationwide data from 2002 to 2007 produced by the National Health Insurance Corporation and the Health Insurance Review & Assessment Service. The subjects were 336 OBGYN clinics consisting of 43 DRG clinics that had maintained their participation in 2003-2007 and 293 no-DRG (fee-for-service) clinics that had never been a DRG clinic during the same period. Logistic regression analysis was carried out to determine the factors associated with the participation of OBGYN clinics in the DRG-based payment system. The factors affecting participation of OBGYN clinics in the DRG-based payment system were as follows (psystem are more likely to participate in the DRG-based payment system. Therefore, to ensure adequate participation of physicians, a payment system with a stronger financial incentive might be more suitable in Korea.

Nanopolyaniline as immobilization template for signal enhancement of surface plasmon resonance biosensor - A preliminary study

Science.gov (United States)

Kamarun, Dzaraini; Abdul Azem, Nor Hazirah Kamel; Sarijo, Siti Halimah; Mohd, Ahmad Faiza; Abdullah @ Mohd Noor, Mashita

2012-07-01

A technique for the enhancement of Surface Plasmon Resonance (SPR) signal for sensing biomolecular interactions is described. Polyaniline (PANI) of particle size in the range of 1 to 15 nm was synthesized and used as the template for the immobilization of protein molecules. Biomolecular interactions of unbound and PANI-bound proteins with antibody molecules were SPR-monitored using a model system comprising of Bovine Serum Albumin (BSA) and anti BSA. A 7-fold increased in the signal was recorded from interactions of the PANI-bound BSA with anti BSA compared to the interactions of its unbound counterpart. This preliminary observation provides new avenue in immunosensor technology for improving the detection sensitivity of SPR biosensor; and thereby increasing the lower detection limit of biomolecules.

Production and characterization of protonated molecular clusters containing a given number of water molecules with the DIAM set-up

International Nuclear Information System (INIS)

Bruny, G.

2010-01-01

nano-scale characterization of irradiation in bio-molecular systems requires observation of novel features which are now achievable with the recent technical progress. This work is a central part in the development of DIAM which is a new experimental set-up devoted to irradiation of bio-molecular clusters at the Institut de Physique Nucleaire de Lyon. The development of the cluster source and of a double focusing mass spectrometer leads to the production of intense beams of mass selected protonated molecular clusters. Combined with this mass selected cluster beams an innovative detection technique is demonstrated in collision induced dissociation experiments. The results contribute to the knowledge of the stability and the structure of the small protonated water clusters and mixed clusters of water and pyridine. (author)

Fully integrated microfluidic measurement system for real-time determination of gas and liquid mixtures composition

NARCIS (Netherlands)

Lötters, Joost Conrad; Groenesteijn, Jarno; van der Wouden, E.J.; Sparreboom, Wouter; Lammerink, Theodorus S.J.; Wiegerink, Remco J.

2015-01-01

We have designed and realised a fully integrated microfluidic measurement system for real-time determination of both flow rate and composition of gas- and liquid mixtures. The system comprises relative permittivity sensors, pressure sensors, a Coriolis flow and density sensor, a thermal flow sensor

Determinants of Point-Of-Sale system adoption: a survey among small retailers in The Netherlands.

NARCIS (Netherlands)

Plomp, M.G.A.; Huiden, R.P.; Batenburg, R.S.

2011-01-01

Several threats affect the survival of small, independent retail companies. Adoption and use of Point-of-Sale (POS) systems may offer important benefits to counter these threats. POS systems are not widely used by these retailers, however. This research investigates the determinants of the adoption

Sex-determination systems and their evolution: Mammals

International Nuclear Information System (INIS)

Colorado Garzon, Fredy A; Matta Camacho, Nubia E; Sanchez, Antonio

2012-01-01

Sex-determination methods are very diverse as they have become an enduring research field, understanding the causes of gonadal development and elucidating the main factors involved in sex-determination of offspring required relating information from far-ranging areas such as cytology, embryology, morphology, molecular biology and even ecology and evolution. This article presents an overview of sex-determination in placental mammals, encompassing several levels of biological organization. The importance of the underlying molecular tools in the context of sex-determination assays and their implications in conservation genetics is also discussed.

Preservation of biomolecules in breast cancer tissue by a formalin-free histology system

Directory of Open Access Journals (Sweden)

Morales Azorides R

2008-01-01

Full Text Available Abstract Background The potential problems associated with the use of formalin in histology, such as health hazards, degradation of RNA and cross-linking of proteins are well recognized. We describe the utilization of a formalin-free fixation and processing system for tissue detection of two important biopredictors in breast cancer – estrogen receptor and HER2 – at the RNA and protein levels. Methods Parallel sections of 62 cases of breast cancer were fixed in an alcohol-based molecular fixative and in formalin. Molecular fixative samples were processed by a novel formalin-free microwave-assisted processing system that preserves DNA, RNA and proteins. Formalin-fixed samples were processed using the conventional method. Estrogen receptor was assessed by immunohistochemistry and real-time PCR. HER2 was assessed by immunohistochemistry, FISH, CISH and real-time PCR. Results The immunohistochemical reaction for estrogen receptor was similar in molecular- and formalin-fixed samples (Spearman Rank R = 0.83, p Conclusion The formalin-free tissue fixation and processing system is a practical platform for evaluation of biomolecular markers in breast cancer and it allows reliable DNA and RNA and protein studies.

What determines social capital in a social-ecological system? Insights from a network perspective.

Science.gov (United States)

Barnes-Mauthe, Michele; Gray, Steven Allen; Arita, Shawn; Lynham, John; Leung, PingSun

2015-02-01

Social capital is an important resource that can be mobilized for purposive action or competitive gain. The distribution of social capital in social-ecological systems can determine who is more productive at extracting ecological resources and who emerges as influential in guiding their management, thereby empowering some while disempowering others. Despite its importance, the factors that contribute to variation in social capital among individuals have not been widely studied. We adopt a network perspective to examine what determines social capital among individuals in social-ecological systems. We begin by identifying network measures of social capital relevant for individuals in this context, and review existing evidence concerning their determinants. Using a complete social network dataset from Hawaii's longline fishery, we employ social network analysis and other statistical methods to empirically estimate these measures and determine the extent to which individual stakeholder attributes explain variation within them. We find that ethnicity is the strongest predictor of social capital. Measures of human capital (i.e., education, experience), years living in the community, and information-sharing attitudes are also important. Surprisingly, we find that when controlling for other factors, industry leaders and formal fishery representatives are generally not well connected. Our results offer new quantitative insights on the relationship between stakeholder diversity, social networks, and social capital in a coupled social-ecological system, which can aid in identifying barriers and opportunities for action to overcome resource management problems. Our results also have implications for achieving resource governance that is not only ecologically and economically sustainable, but also equitable.

What Determines Social Capital in a Social-Ecological System? Insights from a Network Perspective

Science.gov (United States)

Barnes-Mauthe, Michele; Gray, Steven Allen; Arita, Shawn; Lynham, John; Leung, PingSun

2015-02-01

Social capital is an important resource that can be mobilized for purposive action or competitive gain. The distribution of social capital in social-ecological systems can determine who is more productive at extracting ecological resources and who emerges as influential in guiding their management, thereby empowering some while disempowering others. Despite its importance, the factors that contribute to variation in social capital among individuals have not been widely studied. We adopt a network perspective to examine what determines social capital among individuals in social-ecological systems. We begin by identifying network measures of social capital relevant for individuals in this context, and review existing evidence concerning their determinants. Using a complete social network dataset from Hawaii's longline fishery, we employ social network analysis and other statistical methods to empirically estimate these measures and determine the extent to which individual stakeholder attributes explain variation within them. We find that ethnicity is the strongest predictor of social capital. Measures of human capital (i.e., education, experience), years living in the community, and information-sharing attitudes are also important. Surprisingly, we find that when controlling for other factors, industry leaders and formal fishery representatives are generally not well connected. Our results offer new quantitative insights on the relationship between stakeholder diversity, social networks, and social capital in a coupled social-ecological system, which can aid in identifying barriers and opportunities for action to overcome resource management problems. Our results also have implications for achieving resource governance that is not only ecologically and economically sustainable, but also equitable.

PELE web server: atomistic study of biomolecular systems at your fingertips.

Science.gov (United States)

Madadkar-Sobhani, Armin; Guallar, Victor

2013-07-01

PELE, Protein Energy Landscape Exploration, our novel technology based on protein structure prediction algorithms and a Monte Carlo sampling, is capable of modelling the all-atom protein-ligand dynamical interactions in an efficient and fast manner, with two orders of magnitude reduced computational cost when compared with traditional molecular dynamics techniques. PELE's heuristic approach generates trial moves based on protein and ligand perturbations followed by side chain sampling and global/local minimization. The collection of accepted steps forms a stochastic trajectory. Furthermore, several processors may be run in parallel towards a collective goal or defining several independent trajectories; the whole procedure has been parallelized using the Message Passing Interface. Here, we introduce the PELE web server, designed to make the whole process of running simulations easier and more practical by minimizing input file demand, providing user-friendly interface and producing abstract outputs (e.g. interactive graphs and tables). The web server has been implemented in C++ using Wt (http://www.webtoolkit.eu) and MySQL (http://www.mysql.com). The PELE web server, accessible at http://pele.bsc.es, is free and open to all users with no login requirement.

Improved Parameters for the Martini Coarse-Grained Protein Force Field

NARCIS (Netherlands)

de Jong, Djurre H.; Singh, Gurpreet; Bennett, W. F. Drew; Arnarez, Clement; Wassenaar, Tsjerk A.; Schafer, Lars V.; Periole, Xavier; Tieleman, D. Peter; Marrink, Siewert J.

The Martini coarse-grained force field has been successfully used for simulating a wide range of (bio)molecular systems. Recent progress in our ability to test the model against fully atomistic force fields, however, has revealed some shortcomings. Most notable, phenylalanine and proline were too

Sex determination

Indian Academy of Sciences (India)

The sex-determining system differs considerably among organisms. Even among insect species, the genetic system for sex-determination is highly diversified. In Drosophila melanogaster, somatic sexual differentiation is regulated by a well characterized genetic hierarchy X : A > Sxl > tra/tra2 > dsx and fru. This cascade ...

GMR biosensor arrays: a system perspective.

Science.gov (United States)

Hall, D A; Gaster, R S; Lin, T; Osterfeld, S J; Han, S; Murmann, B; Wang, S X

2010-05-15

Giant magnetoresistive biosensors are becoming more prevalent for sensitive, quantifiable biomolecular detection. However, in order for magnetic biosensing to become competitive with current optical protein microarray technology, there is a need to increase the number of sensors while maintaining the high sensitivity and fast readout time characteristic of smaller arrays (1-8 sensors). In this paper, we present a circuit architecture scalable for larger sensor arrays (64 individually addressable sensors) while maintaining a high readout rate (scanning the entire array in less than 4s). The system utilizes both time domain multiplexing and frequency domain multiplexing in order to achieve this scan rate. For the implementation, we propose a new circuit architecture that does not use a classical Wheatstone bridge to measure the small change in resistance of the sensor. Instead, an architecture designed around a transimpedance amplifier is employed. A detailed analysis of this architecture including the noise, distortion, and potential sources of errors is presented, followed by a global optimization strategy for the entire system comprising the magnetic tags, sensors, and interface electronics. To demonstrate the sensitivity, quantifiable detection of two blindly spiked samples of unknown concentrations has been performed at concentrations below the limit of detection for the enzyme-linked immunosorbent assay. Lastly, the multiplexing capability and reproducibility of the system was demonstrated by simultaneously monitoring sensors functionalized with three unique proteins at different concentrations in real-time. 2010 Elsevier B.V. All rights reserved.

Determination of the gamma radiation scattering with geometry changes in the system

International Nuclear Information System (INIS)

Albuquerque, M. da P.P.; Xavier, M.; Caldas, L.V.E.

1988-07-01

Three different experimental systems were used for the determination of the radiation scattering due to the walls, ceiling and floor of the Calibration Laboratory. The radiation detection was made with a portable ionization chamber Victoreen model Panoramic 470. The measurements were taken with and without the use of a lead shield block between the detector and the radioactive source. The results showed that the scattering contribution increased about 80%, as the distance between detector and source was varied from 1,0 to 2,0 m. Therefore the scattering contribution determination is very important for the establishment of the standard radiation fields for instruments calibration. (author) [pt

Designing a reusable system based on nanodiamonds for biochemical determination of urea.

Science.gov (United States)

Ronzhin, N O; Baron, A V; Bondar, V S; Gitelson, I I

2015-01-01

A reusable system including urease covalently bound to the surface of modified nanodiamonds (MNDs) has been developed for the multiple determination of urea. The immobilized enzyme exhibits functional activity and catalyzes the hydrolysis of urea to yield ammonia. The presence of ammonia is confirmed by the formation of a colored product after the addition of chemical reagents. It was shown that the MNDs-urease complex can function in a wide range of temperatures and pH as well as in deionized water. The complex provides a linear yield of the product at low analyte concentrations and allows the multiple determination of urea in vitro.

Determining the Conditions for the Hydraulic Impacts Emergence at Hydraulic Systems

Directory of Open Access Journals (Sweden)

Mazurenko A.S.

2017-08-01

Full Text Available This research aim is to develop a method for modeling the conditions for the critical hydrau-lic impacts emergence on thermal and nuclear power plants’ pipeline systems pressure pumps depart-ing from the general provisions of the heat and hydrodynamic instability theory. On the developed method basis, the conditions giving rise to the reliability-critical hydraulic impacts emergence on pumps for the thermal and nuclear power plants’ typical pipeline system have been determined. With the flow characteristic minimum allowable (critical sensitivity, the flow velocity fluctuations ampli-tude reaches critical values at which the pumps working elements’ failure occurs. The critical hydrau-lic impacts emergence corresponds to the transition of the vibrational heat-hydrodynamic instability into an aperiodic one. As research revealed, a highly promising approach as to the preventing the criti-cal hydraulic impacts related to the foreground use of pumps having the most sensitive consumption (at supply network performance (while other technical characteristics corresponding to that parame-ter. The research novelty refers to the suggested method elaborated by the authors’ team, which, in contrast to traditional approaches, is efficient in determining the pump hydraulic impact occurrence conditions when the vibrational heat-hydrodynamic instability transition to the aperiodic instability.

Tracer techniques for urine volume determination and urine collection and sampling back-up system

Science.gov (United States)

Ramirez, R. V.

1971-01-01

The feasibility, functionality, and overall accuracy of the use of lithium were investigated as a chemical tracer in urine for providing a means of indirect determination of total urine volume by the atomic absorption spectrophotometry method. Experiments were conducted to investigate the parameters of instrumentation, tracer concentration, mixing times, and methods for incorporating the tracer material in the urine collection bag, and to refine and optimize the urine tracer technique to comply with the Skylab scheme and operational parameters of + or - 2% of volume error and + or - 1% accuracy of amount of tracer added to each container. In addition, a back-up method for urine collection and sampling system was developed and evaluated. This back-up method incorporates the tracer technique for volume determination in event of failure of the primary urine collection and preservation system. One chemical preservative was selected and evaluated as a contingency chemical preservative for the storage of urine in event of failure of the urine cooling system.

Determination of tributyl phosphate (TBP) by precision densimetry : TBP-varsol-HNO/sub 3/ system

Energy Technology Data Exchange (ETDEWEB)

Matsuda, H T; Araujo, B.F. de; Araujo, J.A. de [Instituto de Pesquisas Energeticas e Nucleares, Sao Paulo (Brazil). Centro de Engenharia Quimica

1980-01-01

A simple and rapid method for TBP direct determination is presented, based on precision densimetry, aiming to control solvent concentration in the TBP-Varsol system during the reprocessing of irradiated uranium. The method comprises the determination of the density of liquids or gases by electronic measurement of the variation in the frequency (f) or period (T = 1/f) of a glass oscillator containing the liquid or the gas.

A chromatographic determination of water in non-aqueous phases of solvent extraction systems

International Nuclear Information System (INIS)

Lyle, S.J.; Smith, D.B.

1975-01-01

The disadvantages of the Karl Fischer method for the determination of water in the non-aqueous phases of solvent extraction systems are pointed out, and a gas chromatographic method is described which is claimed to be potentially capable of overcoming these disadvantages. The method, as described, was developed to satisfy conditions relevant to measurement of the transfer rate of water from an aqueous phase into tri-n-butylphosphate in toluene, but it can be used for water determination in other solvent extraction systems. The apparatus used is described in detail. The concentration of water in water-saturated TBP was found to be 3.56 mol/litre, compared with a value of 3.55 obtained by Karl Fischer titration and previous literature values of 3.59 and 3.57. Measurements of water content in benzene solutions of long chain alkylamines were also sucessfully carried out. (U.K.)

DETERMINING THE THERMAL RESISTANCE OF A VENTILATED HINGED FACADE SYSTEM LAYER

Directory of Open Access Journals (Sweden)

Gagarin Vladimir Gennad'evich

2015-03-01

Full Text Available Enveloping structures with hinged façade systems are nowadays widely used for moisture control of enveloping structures, prevention of overheating of the structures by insolation, saving the constructions from atmospheric moisture and also for correspondence with the raised requirements to thermal protection of the enveloping structures, aimed also at reducing energy consumption. In the winter conditions the influence of air layer on the thermal insulation parameters is usually neglected. In the article the thermal resistance of an air gap and is considered and its effect in the calculation of the heat resistance of a building envelope with hinged facade system is analyzed in the conditions of cold weather. The thermal resistance of the air layer determines how the heat losses decrease.

Expert System for Determination of Type Lenses Glasses Using Forward Chaining Method

Directory of Open Access Journals (Sweden)

Atikah Ari Pramesti

2016-11-01

Full Text Available One of the branches of computer science that is widely used by humans to help her work is the establishment of an expert system. In this study we will design an expert system for determining the type of spectacle lenses using a forward chaining method. In forward chaining method, starting with the initial information (early symptoms and moved forward to fit more information to find the information in accordance with the rules of the knowledge base and production, and will be concluded in the form of the type of disorder diagnosis of eye disorders and provide solutions in the form of lenses of eyeglasses. Result from this study is that the match calculation of algorithm of forward chaining method between system and manual calculations produce the same output.

Extending the self-assembly of coiled-coil hybrids

NARCIS (Netherlands)

Robson Marsden, Hana

2009-01-01

Of the various biomolecular building blocks in use in nature, coiled-coil forming peptides are amongst those with the most potential as building blocks for the synthetic self-assembly of nanostructures. Native coiled coils have the ability to function in, and influence, complex systems composed of

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

Hemi-ordered nanoporous carbon electrode material for highly selective determination of nitrite in physiological and environmental systems

Energy Technology Data Exchange (ETDEWEB)

Zhou, Shenghai; Wu, Hongmin; Wu, Ying; Shi, Hongyan; Feng, Xun; Jiang, Shang; Chen, Jian; Song, Wenbo, E-mail: wbsong@jlu.edu.cn

2014-08-01

Hemi-ordered nanoporous carbon (HONC) was obtained from a mesoporous silica template through a nano-replication method using furfuryl alcohol as the carbon source. The structure and morphology of HONC were characterized and analyzed in detail by X-ray diffraction, N{sub 2}-sorption, Raman spectroscopy and transmission electron microscopy. HONC was then demonstrated as active electrode material for selective determination of nitrite in either physiological or environmental system. Well separated oxidation peaks of ascorbic acid, dopamine, uric acid and nitrite were observed in physiological system, and simultaneous discrimination of catechol, hydroquinone, resorcinol and nitrite in environmental system was also accomplished. Distinctly improved performances for selective determination of nitrite (such as significantly fast and sensitive current response with especially high selectivity) coexisted with ascorbic acid, dopamine and uric acid in the physiological system, as well as with catechol, hydroquinone and resorcinol in the environmental system were achieved at HONC electrode material. The excellent discriminating ability and high selectivity for NO{sub 2}{sup −} determination were ascribed to the good electronic conductivity, unique hemi-ordered porous structure, large surface area and large number of edge plane defect sites contained on the surface of nanopore walls of HONC. Results in this work demonstrated that HONC is one of the promising catalytic electrode materials for nitrite sensor fabrication. - Highlights: • Hemi-ordered nanoporous carbon as an active electrode material • Good discriminating ability towards NO{sub 2}{sup −} from physiological or environmental system • Highly selective determination of nitrite with fast and sensitive current response.

Reduction of Under-Determined Linear Systems by Sparce Block Matrix Technique

DEFF Research Database (Denmark)

Tarp-Johansen, Niels Jacob; Poulsen, Peter Noe; Damkilde, Lars

1996-01-01

numerical stability of the aforementioned reduction. Moreover the coefficient matrix for the equilibrium equations is typically very sparse. The objective is to deal efficiently with the full pivoting reduction of sparse rectangular matrices using a dynamic storage scheme based on the block matrix concept.......Under-determined linear equation systems occur in different engineering applications. In structural engineering they typically appear when applying the force method. As an example one could mention limit load analysis based on The Lower Bound Theorem. In this application there is a set of under......-determined equilibrium equation restrictions in an LP-problem. A significant reduction of computer time spent on solving the LP-problem is achieved if the equilib rium equations are reduced before going into the optimization procedure. Experience has shown that for some structures one must apply full pivoting to ensure...

Single x-ray transmission system for bone mineral density determination

International Nuclear Information System (INIS)

Jimenez-Mendoza, Daniel; Vargas-Vazquez, Damian; Espinosa-Arbelaez, Diego G.; Giraldo-Betancur, Astrid L.; Hernandez-Urbiola, Margarita I.; Rodriguez-Garcia, Mario E.

2011-01-01

Bones are the support of the body. They are composed of many inorganic compounds and other organic materials that all together can be used to determine the mineral density of the bones. The bone mineral density is a measure index that is widely used as an indicator of the health of the bone. A typical manner to evaluate the quality of the bone is a densitometry study; a dual x-ray absorptiometry system based study that has been widely used to assess the mineral density of some animals' bones. However, despite the success stories of utilizing these systems in many different applications, it is a very expensive method that requires frequent calibration processes to work properly. Moreover, its usage in small species applications (e.g., rodents) has not been quite demonstrated yet. Following this argument, it is suggested that there is a need for an instrument that would perform such a task in a more reliable and economical manner. Therefore, in this paper we explore the possibility to develop a new, affordable, and reliable single x-ray absorptiometry system. The method consists of utilizing a single x-ray source, an x-ray image sensor, and a computer platform that all together, as a whole, will allow us to calculate the mineral density of the bone. Utilizing an x-ray transmission theory modified through a version of the Lambert-Beer law equation, a law that expresses the relationship among the energy absorbed, the thickness, and the absorption coefficient of the sample at the x-rays wavelength to calculate the mineral density of the bone can be advantageous. Having determined the parameter equation that defines the ratio of the pixels in radiographies and the bone mineral density [measured in mass per unit of area (g/cm 2 )], we demonstrated the utility of our novel methodology by calculating the mineral density of Wistar rats' femur bones.

A model for determining condition-based maintenance policies for deteriorating multi-component systems

NARCIS (Netherlands)

Hontelez, J.A.M.; Wijnmalen, D.J.D.

1993-01-01

We discuss a method to determine strategies for preventive maintenance of systems consisting of gradually deteriorating components. A model has been developed to compute not only the range of conditions inducing a repair action, but also inspection moments based on the last known condition value so

Validation of a MOSFET dosemeter system for determining the absorbed and effective radiation doses in diagnostic radiology.

Science.gov (United States)

Manninen, A-L; Kotiaho, A; Nikkinen, J; Nieminen, M T

2015-04-01

This study aimed to validate a MOSFET dosemeter system for determining absorbed and effective doses (EDs) in the dose and energy range used in diagnostic radiology. Energy dependence, dose linearity and repeatability of the dosemeter were examined. The absorbed doses (ADs) were compared at anterior-posterior projection and the EDs were determined at posterior-anterior, anterior-posterior and lateral projections of thoracic imaging using an anthropomorphic phantom. The radiation exposures were made using digital radiography systems. This study revealed that the MOSFET system with high sensitivity bias supply set-up is sufficiently accurate for AD and ED determination. The dosemeter is recommended to be calibrated for energies 80 kVp. The entrance skin dose level should be at least 5 mGy to minimise the deviation of the individual dosemeter dose. For ED determination, dosemeters should be implanted perpendicular to the surface of the phantom to prevent the angular dependence error. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An inclined plane system with microcontroller to determine limb motor function of laboratory animals.

Science.gov (United States)

Chang, Ming-Wen; Young, Ming-Shing; Lin, Mao-Tsun

2008-02-15

This study describes a high-accuracy inclined plane test system for quantitative measurement of the limb motor function of laboratory rats. The system is built around a microcontroller and uses a stepping motor to drive a ball screw, which changes the angle of the inclined plane. Any of the seven inclination speeds can be selected by the user. Two infrared (IR) LED/detector pairs function as interrupt sensors for objective determination of the moment that the rat loses its grip on the textured flooring of the starting area and slips down the plane. Inclination angle at the moment of IR interrupt (i.e. rat slip) is recorded. A liquid crystal display module shows the inclination speed and the inclination angle. The system can function as a stand alone device but a RS232 port allows connection to a personal computer (PC), so data can be sent directly to hard disk for storage and analysis. Experiments can be controlled by a local keypad or by the connected PC. Advantages of the presented system include easy operation, high accuracy, non-dependence on human observation for determination of slip angle, stand-alone capability, low cost and easy modification of the controlling software for different types of experiments. A fully functional prototype of the system is described. The prototype was used experimentally by a hospital group testing traumatic brain injury experiments, and some of their results are presented for system verification. It is found that the system is stable, accurate and easily used by investigators.

Spectrophotometric determination of phosphorus in iron alloys employing a flow injection system

Directory of Open Access Journals (Sweden)

Gervasio Ana P. G.

2001-01-01

Full Text Available A flow-injection procedure for spectrophotometric determination of phosphorus in electrolytic iron and iron alloys is proposed. The method is based on the ammonium molybdate reaction followed by stannous chloride reduction in acidic medium. In order to circumvent the severe interference caused by the major constituents such as Fe(III and Cr(III, a mini-column packed with AG50W-X8 resin was coupled to the manifold. A sample throughput of 40 determinations per hour, a dynamical range from P 0.25 to 6.00 mg L-1, a reagent consumption of 25 mg ammonium molybdate and 2 mg stannous chloride per determination, and a relative standard deviation < 1% (n = 10 for a typical sample with 2.20 mg L-1 P were achieved. Three different types of samples were used to evaluate system performance. Accuracy was assessed by comparing the results with certified values and no significant difference at 95 % confidence level was observed.

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.

Biomolecular detection device

Science.gov (United States)

Huo, Qisheng [Albuquerque, NM; Liu, Jun [Albuquerque, NM

2008-10-21

A device for detecting and measuring the concentration of biomolecules in solution, utilizing a conducting electrode in contact with a solution containing target biomolecules, with a film with controllable pore size distribution characteristics applied to at least one surface of the conducting electrode. The film is functionalized with probe molecules that chemically interact with the target biomolecules at the film surface, blocking indicator molecules present in solution from diffusing from the solution to the electrode, thereby changing the electrochemical response of the electrode.

MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations

OpenAIRE

Vergara-Perez, Sandra; Marucho, Marcelo

2015-01-01

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, de...

Analysis of nanoparticle biomolecule complexes.

Science.gov (United States)

Gunnarsson, Stefán B; Bernfur, Katja; Mikkelsen, Anders; Cedervall, Tommy

2018-03-01

Nanoparticles exposed to biological fluids adsorb biomolecules on their surface forming a biomolecular corona. This corona determines, on a molecular level, the interactions and impact the newly formed complex has on cells and organisms. The corona formation as well as the physiological and toxicological relevance are commonly investigated. However, an acknowledged but rarely addressed problem in many fields of nanobiotechnology is aggregation and broadened size distribution of nanoparticles following their interactions with the molecules of biological fluids. In blood serum, TiO 2 nanoparticles form complexes with a size distribution from 30 nm to more than 500 nm. In this study we have separated these complexes, with good resolution, using preparative centrifugation in a sucrose gradient. Two main apparent size populations were obtained, a fast sedimenting population of complexes that formed a pellet in the preparative centrifugation tube, and a slow sedimenting complex population still suspended in the gradient after centrifugation. Concentration and surface area dependent differences are found in the biomolecular corona between the slow and fast sedimenting fractions. There are more immunoglobulins, lipid binding proteins, and lipid-rich complexes at higher serum concentrations. Sedimentation rate and the biomolecular corona are important factors for evaluating any experiment including nanoparticle exposure. Our results show that traditional description of nanoparticles in biological fluids is an oversimplification and that more thorough characterisations are needed.

Determination of Conjugation Efficiency of Antibodies and Proteins to the Superparamagnetic Iron Oxide Nanoparticles by Capillary Electrophoresis with Laser-Induced Fluorescence Detection

Energy Technology Data Exchange (ETDEWEB)

Wang, F.-H.; Yoshitake, Takashi [Karolinska Institutet, Department of Neuroscience (Sweden); Kim, Do-Kyung; Muhammed, Mamoun [Royal Institute of Technology, Materials Chemistry Division (Sweden); Bjelke, Boerje [MRI-Center, Experimental Unit, Karolinska Institutet (Sweden); Kehr, Jan [Karolinska Institutet, Department of Neuroscience (Sweden)], E-mail: Jan.Kehr@neuro.ki.se

2003-04-15

The method based on capillary electrophoresis with laser-induced fluorescence detection (CE/LIF) was developed for determination of magnetic iron oxide nanoparticles (hydrodynamic diameters of 100 nm) functionalized with molecules containing primary amino groups. The magnetic nanoparticles with carboxylic or aminopropyl-trimethoxysilane groups at their surface were conjugated to the model proteins (bovine serum albumin, BSA; streptavidin or goat anti-rabbit immunoglobulin G, IgG) using carbodiimide as a zero-length cross-linker.The nanoparticle-protein conjugates (hydrodynamic diameter 163-194 nm) were derivatized with naphthalene-2,3-dicarboxaldehyde reagent and separated by CE/LIF with a helium-cadmium laser (excitation at 442 nm, emission at 488 nm). The separations were carried out by using a fused-silica capillary (effective length 48 cm, inner diameter 75 um) and 100 mM sodium borate buffer (pH 9.2), the potential was 30 kV. The detection limit for BSA-conjugate was 1.3 pg/10 nl, i.e. about 20 amol. The present method provides an efficient and fast tool for sensitive determination of the efficacy of biomolecular functionalization of magnetic nanoparticles. The CE/LIF technique requires only negligible sample volumes for analysis, which is especially suitable for controlling the process of preparation of functionalized nanoparticles with unique properties aimed to be used for diagnostic or therapeutic purposes.

Robust Floor Determination Algorithm for Indoor Wireless Localization Systems under Reference Node Failure

Directory of Open Access Journals (Sweden)

Kriangkrai Maneerat

2016-01-01

Full Text Available One of the challenging problems for indoor wireless multifloor positioning systems is the presence of reference node (RN failures, which cause the values of received signal strength (RSS to be missed during the online positioning phase of the location fingerprinting technique. This leads to performance degradation in terms of floor accuracy, which in turn affects other localization procedures. This paper presents a robust floor determination algorithm called Robust Mean of Sum-RSS (RMoS, which can accurately determine the floor on which mobile objects are located and can work under either the fault-free scenario or the RN-failure scenarios. The proposed fault tolerance floor algorithm is based on the mean of the summation of the strongest RSSs obtained from the IEEE 802.15.4 Wireless Sensor Networks (WSNs during the online phase. The performance of the proposed algorithm is compared with those of different floor determination algorithms in literature. The experimental results show that the proposed robust floor determination algorithm outperformed the other floor algorithms and can achieve the highest percentage of floor determination accuracy in all scenarios tested. Specifically, the proposed algorithm can achieve greater than 95% correct floor determination under the scenario in which 40% of RNs failed.