WorldWideScience

Sample records for biomolecular interaction forces

  1. 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.

  2. Exploring Biomolecular Interactions Through Single-Molecule Force Spectroscopy and Computational Simulation

    OpenAIRE

    Yang, Darren

    2016-01-01

    Molecular interactions between cellular components such as proteins and nucleic acids govern the fundamental processes of living systems. Technological advancements in the past decade have allowed the characterization of these molecular interactions at the single-molecule level with high temporal and spatial resolution. Simultaneously, progress in computer simulation has enabled theoretical research at the atomistic level, assisting in the interpretation of experimental results. This thesi...

  3. Chiral interaction and biomolecular evolution

    International Nuclear Information System (INIS)

    Gilat, G.

    1992-01-01

    Recent developments in the concept of chiral interaction open now new options and dynamical possibilities for biomolecules which have so far been overlooked. A few of these possibilities are mentioned, such as the control mechanism of enzymatic activity and the role played by non-ergodicity in evolutionary processes. It is shown that chiral interaction, being a surface phenomenon, does not obey Barron's symmetry constraints, which are suitable for force fields present in bulk interactions. In particular, the situation at the ocean-air surface in the prebiotic era is described, as well as the possible role played by chiral interaction in conjunction with the terrestrial magnetic field normal to the ocean surface, which could have lead to a process of deracernization at the ocean-air interface. (author)

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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)

  10. 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

  11. 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...

  12. 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

  13. The MARTINI force field : Coarse grained model for biomolecular simulations

    NARCIS (Netherlands)

    Marrink, Siewert J.; Risselada, H. Jelger; Yefimov, Serge; Tieleman, D. Peter; de Vries, Alex H.

    2007-01-01

    We present an improved and extended version of our coarse grained lipid model. The new version, coined the MARTINI force field, is parametrized in a systematic way, based on the reproduction of partitioning free energies between polar and apolar phases of a large number of chemical compounds. To

  14. 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

  15. 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.

  16. 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...

  17. 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.

  18. Biomolecular Interactions of Tannin Isolated from Oenothera gigas with Liposomes.

    Science.gov (United States)

    Sekowski, Szymon; Ionov, Maksim; Dubis, Alina; Mavlyanov, Saidmukhtar; Bryszewska, Maria; Zamaraeva, Maria

    2016-04-01

    We have examined the interaction between hydrolysable tannin 1-O-galloyl-4,6-hexahydroxydiphenoyl-β-D-glucose (OGβDG) with neutral liposomes as a model of cell membranes composed of three lipids: lecithin, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) at different mass ratios. OGβDG in the concentration range 0.5-15 µg/ml (0.4-12 µM) strongly interacts with liposomal membranes by changing their structure, surface charge and fluidity. Used OGβDG molecules decrease and increase the rigidity of hydrophilic surface and hydrophobic parts of liposomes, respectively. At higher concentrations of tannin (>15 µM), liposomes are aggregated. Fourier Transform Infra-Red (FTIR) analysis showed that mainly -OH groups from OGβDG and also PO(2-) groups from phospholipids are responsible for the interaction. Obtained data indicate the importance of membrane lipid composition in interactions between tannins and cells.

  19. Exploring biomolecular dynamics and interactions using advanced sampling methods

    International Nuclear Information System (INIS)

    Luitz, Manuel; Bomblies, Rainer; Ostermeir, Katja; Zacharias, Martin

    2015-01-01

    Molecular dynamics (MD) and Monte Carlo (MC) simulations have emerged as a valuable tool to investigate statistical mechanics and kinetics of biomolecules and synthetic soft matter materials. However, major limitations for routine applications are due to the accuracy of the molecular mechanics force field and due to the maximum simulation time that can be achieved in current simulations studies. For improving the sampling a number of advanced sampling approaches have been designed in recent years. In particular, variants of the parallel tempering replica-exchange methodology are widely used in many simulation studies. Recent methodological advancements and a discussion of specific aims and advantages are given. This includes improved free energy simulation approaches and conformational search applications. (topical review)

  20. UV-SPR biosensor for biomolecular interaction studies

    Science.gov (United States)

    Geiss, F. A.; Fossati, S.; Khan, I.; Gisbert Quilis, N.; Knoll, W.; Dostalek, J.

    2017-05-01

    UV surface plasmon resonance (SPR) for direct in situ detection of protein binding events is reported. A crossed relief aluminum grating was employed for diffraction coupling to surface plasmons as an alternative to more commonly used attenuated total reflection method. Wavelength interrogation of SPR was carried out by using transmission measurements in order to probe odorant-binding protein 14 (OBP14) of the honey bee (Apis mellifera). The native oxide layer on the top of an aluminum grating sensor chip allows for covalent coupling of protein molecules by using regular silane-based linkers. The probing of bound OBP14 protein at UV with confined field of surface plasmons holds potential for further studies of interaction with recently developed artificial fluorescent odorants.

  1. 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.

  2. Analysis of DNA interactions using single-molecule force spectroscopy.

    Science.gov (United States)

    Ritzefeld, Markus; Walhorn, Volker; Anselmetti, Dario; Sewald, Norbert

    2013-06-01

    Protein-DNA interactions are involved in many biochemical pathways and determine the fate of the corresponding cell. Qualitative and quantitative investigations on these recognition and binding processes are of key importance for an improved understanding of biochemical processes and also for systems biology. This review article focusses on atomic force microscopy (AFM)-based single-molecule force spectroscopy and its application to the quantification of forces and binding mechanisms that lead to the formation of protein-DNA complexes. AFM and dynamic force spectroscopy are exciting tools that allow for quantitative analysis of biomolecular interactions. Besides an overview on the method and the most important immobilization approaches, the physical basics of the data evaluation is described. Recent applications of AFM-based force spectroscopy to investigate DNA intercalation, complexes involving DNA aptamers and peptide- and protein-DNA interactions are given.

  3. 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

  4. 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

  5. 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.

  6. Review of Transducer Principles for Label-Free Biomolecular Interaction Analysis

    Directory of Open Access Journals (Sweden)

    Janos Vörös

    2011-07-01

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

  7. 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.

  8. Prediction of Biomolecular Complexes

    KAUST Repository

    Vangone, Anna

    2017-04-12

    Almost all processes in living organisms occur through specific interactions between biomolecules. Any dysfunction of those interactions can lead to pathological events. Understanding such interactions is therefore a crucial step in the investigation of biological systems and a starting point for drug design. In recent years, experimental studies have been devoted to unravel the principles of biomolecular interactions; however, due to experimental difficulties in solving the three-dimensional (3D) structure of biomolecular complexes, the number of available, high-resolution experimental 3D structures does not fulfill the current needs. Therefore, complementary computational approaches to model such interactions are necessary to assist experimentalists since a full understanding of how biomolecules interact (and consequently how they perform their function) only comes from 3D structures which provide crucial atomic details about binding and recognition processes. In this chapter we review approaches to predict biomolecular complexesBiomolecular complexes, introducing the concept of molecular dockingDocking, a technique which uses a combination of geometric, steric and energetics considerations to predict the 3D structure of a biological complex starting from the individual structures of its constituent parts. We provide a mini-guide about docking concepts, its potential and challenges, along with post-docking analysis and a list of related software.

  9. Prediction of Biomolecular Complexes

    KAUST Repository

    Vangone, Anna; Oliva, Romina; Cavallo, Luigi; Bonvin, Alexandre M. J. J.

    2017-01-01

    Almost all processes in living organisms occur through specific interactions between biomolecules. Any dysfunction of those interactions can lead to pathological events. Understanding such interactions is therefore a crucial step in the investigation of biological systems and a starting point for drug design. In recent years, experimental studies have been devoted to unravel the principles of biomolecular interactions; however, due to experimental difficulties in solving the three-dimensional (3D) structure of biomolecular complexes, the number of available, high-resolution experimental 3D structures does not fulfill the current needs. Therefore, complementary computational approaches to model such interactions are necessary to assist experimentalists since a full understanding of how biomolecules interact (and consequently how they perform their function) only comes from 3D structures which provide crucial atomic details about binding and recognition processes. In this chapter we review approaches to predict biomolecular complexesBiomolecular complexes, introducing the concept of molecular dockingDocking, a technique which uses a combination of geometric, steric and energetics considerations to predict the 3D structure of a biological complex starting from the individual structures of its constituent parts. We provide a mini-guide about docking concepts, its potential and challenges, along with post-docking analysis and a list of related software.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Combinatorial solid-phase glycopeptide libraries - Synthesis and application in biomolecular interaction studies and biosensors

    NARCIS (Netherlands)

    Maljaars, C.E.P.

    2006-01-01

    Carbohydrates play vital roles in all forms of life. Attached to proteins and lipids they serve as recognition elements in several biological interaction processes, such as intercellular communication, immune response, viral and parasitical infections, signal transduction, and development. Synthetic

  15. S66: A Well-balanced Database of Benchmark Interaction Energies Relevant to Biomolecular Structures

    Czech Academy of Sciences Publication Activity Database

    Řezáč, Jan; Riley, Kevin Eugene; Hobza, Pavel

    2011-01-01

    Roč. 7, č. 8 (2011), s. 2427-2438 ISSN 1549-9618 R&D Projects: GA MŠk LC512 Institutional research plan: CEZ:AV0Z40550506 Keywords : noncovalent interactions * benchmarking * CCSD(T) Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.215, year: 2011

  16. Module discovery by exhaustive search for densely connected, co-expressed regions in biomolecular interaction networks.

    Directory of Open Access Journals (Sweden)

    Recep Colak

    2010-10-01

    Full Text Available Computational prediction of functionally related groups of genes (functional modules from large-scale data is an important issue in computational biology. Gene expression experiments and interaction networks are well studied large-scale data sources, available for many not yet exhaustively annotated organisms. It has been well established, when analyzing these two data sources jointly, modules are often reflected by highly interconnected (dense regions in the interaction networks whose participating genes are co-expressed. However, the tractability of the problem had remained unclear and methods by which to exhaustively search for such constellations had not been presented.We provide an algorithmic framework, referred to as Densely Connected Biclustering (DECOB, by which the aforementioned search problem becomes tractable. To benchmark the predictive power inherent to the approach, we computed all co-expressed, dense regions in physical protein and genetic interaction networks from human and yeast. An automatized filtering procedure reduces our output which results in smaller collections of modules, comparable to state-of-the-art approaches. Our results performed favorably in a fair benchmarking competition which adheres to standard criteria. We demonstrate the usefulness of an exhaustive module search, by using the unreduced output to more quickly perform GO term related function prediction tasks. We point out the advantages of our exhaustive output by predicting functional relationships using two examples.We demonstrate that the computation of all densely connected and co-expressed regions in interaction networks is an approach to module discovery of considerable value. Beyond confirming the well settled hypothesis that such co-expressed, densely connected interaction network regions reflect functional modules, we open up novel computational ways to comprehensively analyze the modular organization of an organism based on prevalent and largely

  17. Module discovery by exhaustive search for densely connected, co-expressed regions in biomolecular interaction networks.

    Science.gov (United States)

    Colak, Recep; Moser, Flavia; Chu, Jeffrey Shih-Chieh; Schönhuth, Alexander; Chen, Nansheng; Ester, Martin

    2010-10-25

    Computational prediction of functionally related groups of genes (functional modules) from large-scale data is an important issue in computational biology. Gene expression experiments and interaction networks are well studied large-scale data sources, available for many not yet exhaustively annotated organisms. It has been well established, when analyzing these two data sources jointly, modules are often reflected by highly interconnected (dense) regions in the interaction networks whose participating genes are co-expressed. However, the tractability of the problem had remained unclear and methods by which to exhaustively search for such constellations had not been presented. We provide an algorithmic framework, referred to as Densely Connected Biclustering (DECOB), by which the aforementioned search problem becomes tractable. To benchmark the predictive power inherent to the approach, we computed all co-expressed, dense regions in physical protein and genetic interaction networks from human and yeast. An automatized filtering procedure reduces our output which results in smaller collections of modules, comparable to state-of-the-art approaches. Our results performed favorably in a fair benchmarking competition which adheres to standard criteria. We demonstrate the usefulness of an exhaustive module search, by using the unreduced output to more quickly perform GO term related function prediction tasks. We point out the advantages of our exhaustive output by predicting functional relationships using two examples. We demonstrate that the computation of all densely connected and co-expressed regions in interaction networks is an approach to module discovery of considerable value. Beyond confirming the well settled hypothesis that such co-expressed, densely connected interaction network regions reflect functional modules, we open up novel computational ways to comprehensively analyze the modular organization of an organism based on prevalent and largely available large

  18. "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.

  19. Label-free detection of biomolecular interaction — DNA — Antimicrobial peptide binding

    DEFF Research Database (Denmark)

    Fojan, Peter; Jensen, Kasper Risgaard; Gurevich, Leonid

    2011-01-01

    the molecule. In particular, surface plasmon resonance (SPR) sensors have been already demonstrated suitable for food-safety control, label-free screening for various disease markers in bodily fluids, as well as for real-time continuous monitoring of drug levels in intensive care environment. We envisage...... of plasmon based biosensors to the study of the interaction of Antimicrobial peptide IL4 and DNA. Our results indicate high affinity binding between IL4 and DNA thereby preventing DNA replication and eventually killing the affected cell. We speculate that this is common for a large class of Antimicrobial...

  20. Applying Computational Scoring Functions to Assess Biomolecular Interactions in Food Science: Applications to the Estrogen Receptors

    Directory of Open Access Journals (Sweden)

    Francesca Spyrakis

    2016-10-01

    Thus, key computational medicinal chemistry methods like molecular dynamics can be used to decipher protein flexibility and to obtain stable models for docking and scoring in food-related studies, and virtual screening is increasingly being applied to identify molecules with potential to act as endocrine disruptors, food mycotoxins, and new nutraceuticals [3,4,5]. All of these methods and simulations are based on protein-ligand interaction phenomena, and represent the basis for any subsequent modification of the targeted receptor's or enzyme's physiological activity. We describe here the energetics of binding of biological complexes, providing a survey of the most common and successful algorithms used in evaluating these energetics, and we report case studies in which computational techniques have been applied to food science issues. In particular, we explore a handful of studies involving the estrogen receptors for which we have a long-term interest.

  1. Biomolecular EPR spectroscopy

    CERN Document Server

    Hagen, Wilfred Raymond

    2008-01-01

    Comprehensive, Up-to-Date Coverage of Spectroscopy Theory and its Applications to Biological SystemsAlthough a multitude of books have been published about spectroscopy, most of them only occasionally refer to biological systems and the specific problems of biomolecular EPR (bioEPR). Biomolecular EPR Spectroscopy provides a practical introduction to bioEPR and demonstrates how this remarkable tool allows researchers to delve into the structural, functional, and analytical analysis of paramagnetic molecules found in the biochemistry of all species on the planet. A Must-Have Reference in an Intrinsically Multidisciplinary FieldThis authoritative reference seamlessly covers all important bioEPR applications, including low-spin and high-spin metalloproteins, spin traps and spin lables, interaction between active sites, and redox systems. It is loaded with practical tricks as well as do's and don'ts that are based on the author's 30 years of experience in the field. The book also comes with an unprecedented set of...

  2. Biomolecular Science (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2012-04-01

    A brief fact sheet about NREL Photobiology and Biomolecular Science. The research goal of NREL's Biomolecular Science is to enable cost-competitive advanced lignocellulosic biofuels production by understanding the science critical for overcoming biomass recalcitrance and developing new product and product intermediate pathways. NREL's Photobiology focuses on understanding the capture of solar energy in photosynthetic systems and its use in converting carbon dioxide and water directly into hydrogen and advanced biofuels.

  3. 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.

  4. Data Driven, Force Based Interaction for Quadrotors

    Science.gov (United States)

    McKinnon, Christopher D.

    Quadrotors are small and agile, and are becoming more capable for their compact size. They are expected perform a wide variety of tasks including inspection, physical interaction, and formation flight. In all of these tasks, the quadrotors can come into close proximity with infrastructure or other quadrotors, and may experience significant external forces and torques. Reacting properly in each case is essential to completing the task safely and effectively. In this thesis, we develop an algorithm, based on the Unscented Kalman Filter, to estimate such forces and torques without making assumptions about the source of the forces and torques. We then show in experiment how the proposed estimation algorithm can be used in conjunction with controls and machine learning to choose the appropriate actions in a wide variety of tasks including detecting downwash, tracking the wind induced by a fan, and detecting proximity to the wall.

  5. 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.

  6. 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.

  7. 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...

  8. 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 ).

  9. 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 ).

  10. Biomolecular Sciences: uniting Biology and Chemistry

    NARCIS (Netherlands)

    Vrieling, Engel

    2017-01-01

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

  11. 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.

  12. 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

  13. 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.

  14. Depletion interaction measured by colloidal probe atomic force microscopy

    NARCIS (Netherlands)

    Wijting, W.K.; Knoben, W.; Besseling, N.A.M.; Leermakers, F.A.M.; Cohen Stuart, M.A.

    2004-01-01

    We investigated the depletion interaction between stearylated silica surfaces in cyclohexane in the presence of dissolved polydimethylsiloxane by means of colloidal probe atomic force microscopy. We found that the range of the depletion interaction decreases with increasing concentration.

  15. Investigation of the Interaction between Patulin and Human Serum Albumin by a Spectroscopic Method, Atomic Force Microscopy, and Molecular Modeling

    Directory of Open Access Journals (Sweden)

    Li Yuqin

    2014-01-01

    Full Text Available The interaction of patulin with human serum albumin (HSA was studied in vitro under normal physiological conditions. The study was performed using fluorescence, ultraviolet-visible spectroscopy (UV-Vis, circular dichroism (CD, atomic force microscopy (AFM, and molecular modeling techniques. The quenching mechanism was investigated using the association constants, the number of binding sites, and basic thermodynamic parameters. A dynamic quenching mechanism occurred between HSA and patulin, and the binding constants (K were 2.60 × 104, 4.59 × 104, and 7.01 × 104 M−1 at 288, 300, and 310 K, respectively. Based on fluorescence resonance energy transfer, the distance between the HSA and patulin was determined to be 2.847 nm. The ΔG0, ΔH0, and ΔS0 values across various temperatures indicated that hydrophobic interaction was the predominant binding force. The UV-Vis and CD results confirmed that the secondary structure of HSA was altered in the presence of patulin. The AFM results revealed that the individual HSA molecule dimensions were larger after interaction with patulin. In addition, molecular modeling showed that the patulin-HSA complex was stabilized by hydrophobic and hydrogen bond forces. The study results suggested that a weak intermolecular interaction occurred between patulin and HSA. Overall, the results are potentially useful for elucidating the toxigenicity of patulin when it is combined with the biomolecular function effect, transmembrane transport, toxicological, testing and other experiments.

  16. The interaction of 2-mercaptobenzimidazole with human serum albumin as determined by spectroscopy, atomic force microscopy and molecular modeling.

    Science.gov (United States)

    Li, Yuqin; Jia, Baoxiu; Wang, Hao; Li, Nana; Chen, Gaopan; Lin, Yuejuan; Gao, Wenhua

    2013-04-01

    The interaction of 2-mercaptobenzimidazole (MBI) with human serum albumin (HSA) was studied in vitro by equilibrium dialysis under normal physiological conditions. This study used fluorescence, ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FT-IR), circular dichroism (CD) and Raman spectroscopy, atomic force microscopy (AFM) and molecular modeling techniques. Association constants, the number of binding sites and basic thermodynamic parameters were used to investigate the quenching mechanism. Based on the fluorescence resonance energy transfer, the distance between the HSA and MBI was 2.495 nm. The ΔG(0), ΔH(0), and ΔS(0) values across temperature indicated that the hydrophobic interaction was the predominant binding Force. The UV, FT-IR, CD and Raman spectra confirmed that the HSA secondary structure was altered in the presence of MBI. In addition, the molecular modeling showed that the MBI-HSA complex was stabilized by hydrophobic forces, which resulted from amino acid residues. The AFM results revealed that the individual HSA molecule dimensions were larger after interaction with MBI. Overall, this study suggested a method for characterizing the weak intermolecular interaction. In addition, this method is potentially useful for elucidating the toxigenicity of MBI when it is combined with the biomolecular function effect, transmembrane transport, toxicological testing and other experiments. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. 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.

  18. Acoustic interaction forces between small particles in an ideal fluid

    DEFF Research Database (Denmark)

    Silva, Glauber T.; Bruus, Henrik

    2014-01-01

    We present a theoretical expression for the acoustic interaction force between small spherical particles suspended in an ideal fluid exposed to an external acoustic wave. The acoustic interaction force is the part of the acoustic radiation force on one given particle involving the scattered waves...... from the other particles. The particles, either compressible liquid droplets or elastic microspheres, are considered to be much smaller than the acoustic wavelength. In this so-called Rayleigh limit, the acoustic interaction forces between the particles are well approximated by gradients of pair...

  19. 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.

  20. [Interaction of mental health and forced married migrants in Germany].

    Science.gov (United States)

    Kizilhan, Jan

    2015-11-01

    The study examines the interaction of the forced married migrants and the frequency of the psychological illness. Forced-married and not forced-married migrants are compared concerning her psychological illness in psychosomatic clinics in Germany. Forced-married women reported significantly more about psychological illness and have undertaken on average at least four times a suicide attempt. Forced-married women suffer lifelong from this event and need, with taking into account cultural migration-specific aspects, special support in the psychosocial consultation and medical-therapeutic treatment. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Scalable Molecular Dynamics for Large Biomolecular Systems

    Directory of Open Access Journals (Sweden)

    Robert K. Brunner

    2000-01-01

    Full Text Available We present an optimized parallelization scheme for molecular dynamics simulations of large biomolecular systems, implemented in the production-quality molecular dynamics program NAMD. With an object-based hybrid force and spatial decomposition scheme, and an aggressive measurement-based predictive load balancing framework, we have attained speeds and speedups that are much higher than any reported in literature so far. The paper first summarizes the broad methodology we are pursuing, and the basic parallelization scheme we used. It then describes the optimizations that were instrumental in increasing performance, and presents performance results on benchmark simulations.

  2. Protein-Flavonoid Interaction Studies by a Taylor Dispersion Surface Plasmon Resonance (SPR Technique: A Novel Method to Assess Biomolecular Interactions

    Directory of Open Access Journals (Sweden)

    Preejith P. Vachali

    2016-02-01

    Full Text Available Flavonoids are common polyphenolic compounds widely distributed in fruits and vegetables. These pigments have important pharmacological relevance because emerging research suggests possible anti-cancer and anti-inflammatory properties as well other beneficial health effects. These compounds are relatively hydrophobic molecules, suggesting the role of blood transport proteins in their delivery to tissues. In this study, we assess the binding interactions of four flavonoids (kaempferol, luteolin, quercetin, and resveratrol with human serum albumin (HSA, the most abundant protein in the blood, and with glutathione S-transferase pi isoform-1 (GSTP1, an enzyme with well-characterized hydrophobic binding sites that plays an important role in detoxification of xenobiotics with reduced glutathione, using a novel Taylor dispersion surface plasmon resonance (SPR technique. For the first time, HSA sites revealed a high-affinity binding site for flavonoid interactions. Out of the four flavonoids that we examined, quercetin and kaempferol showed the strongest equilibrium binding affinities (KD of 63 ± 0.03 nM and 37 ± 0.07 nM, respectively. GSTP1 displayed lower affinities in the micromolar range towards all of the flavonoids tested. The interactions of flavonoids with HSA and GSTP1 were studied successfully using this novel SPR assay method. The new method is compatible with both kinetic and equilibrium analyses.

  3. From dynamics to structure and function of model biomolecular systems

    NARCIS (Netherlands)

    Fontaine-Vive-Curtaz, F.

    2007-01-01

    The purpose of this thesis was to extend recent works on structure and dynamics of hydrogen bonded crystals to model biomolecular systems and biological processes. The tools that we have used are neutron scattering (NS) and density functional theory (DFT) and force field (FF) based simulation

  4. Inferring Interaction Force from Visual Information without Using Physical Force Sensors.

    Science.gov (United States)

    Hwang, Wonjun; Lim, Soo-Chul

    2017-10-26

    In this paper, we present an interaction force estimation method that uses visual information rather than that of a force sensor. Specifically, we propose a novel deep learning-based method utilizing only sequential images for estimating the interaction force against a target object, where the shape of the object is changed by an external force. The force applied to the target can be estimated by means of the visual shape changes. However, the shape differences in the images are not very clear. To address this problem, we formulate a recurrent neural network-based deep model with fully-connected layers, which models complex temporal dynamics from the visual representations. Extensive evaluations show that the proposed learning models successfully estimate the interaction forces using only the corresponding sequential images, in particular in the case of three objects made of different materials, a sponge, a PET bottle, a human arm, and a tube. The forces predicted by the proposed method are very similar to those measured by force sensors.

  5. Detection of magnetic-labeled antibody specific recognition events by combined atomic force and magnetic force microscopy

    International Nuclear Information System (INIS)

    Hong Xia; Liu Yanmei; Li Jun; Guo Wei; Bai Yubai

    2009-01-01

    Atomic force (AFM) and magnetic force microscopy (MFM) were developed to detect biomolecular specific interaction. Goat anti-mouse immunoglobulin (anti-IgG) was covalently attached onto gold substrate modified by a self-assembly monolayer of thioctic acid via 1-ethyl-3-[3-(dimethylamino) propyl] carbodiimide (EDC) activation. Magnetic-labeled IgG then specifically adsorbed onto anti-IgG surface. The morphological variation was identified by AFM. MFM was proved to be a fine assistant tool to distinguish the immunorecognized nanocomposites from the impurities by detection of the magnetic signal from magnetic-labeled IgG. It would enhance the understanding of biomolecular recognition process.

  6. Detection of magnetic-labeled antibody specific recognition events by combined atomic force and magnetic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Hong Xia [Center for Advanced Optoelectronic Functional Materials Research, Key Laboratory of UV Light-Emitting Materials and Technology, Ministry of Education, Northeast Normal University, Changchun 130024 (China); College of Chemistry, Jilin University, Changchun 130023 (China)], E-mail: xiahong@nenu.edu.cn; Liu Yanmei; Li Jun; Guo Wei; Bai Yubai [College of Chemistry, Jilin University, Changchun 130023 (China)

    2009-09-15

    Atomic force (AFM) and magnetic force microscopy (MFM) were developed to detect biomolecular specific interaction. Goat anti-mouse immunoglobulin (anti-IgG) was covalently attached onto gold substrate modified by a self-assembly monolayer of thioctic acid via 1-ethyl-3-[3-(dimethylamino) propyl] carbodiimide (EDC) activation. Magnetic-labeled IgG then specifically adsorbed onto anti-IgG surface. The morphological variation was identified by AFM. MFM was proved to be a fine assistant tool to distinguish the immunorecognized nanocomposites from the impurities by detection of the magnetic signal from magnetic-labeled IgG. It would enhance the understanding of biomolecular recognition process.

  7. Monitoring ligand-receptor interactions by photonic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-06-25

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

  8. Monitoring ligand-receptor interactions by photonic force microscopy

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  9. Study of Adhesion Interaction Using Atomic Force Microscopy

    Science.gov (United States)

    Grybos, J.; Pyka-Fosciak, G.; Lebed, K.; Lekka, M.; Stachura, Z.; Styczeñ, J.

    2003-05-01

    An atomic force microscope is a useful tool to study the interaction forces at molecular level. In particular the atomic force microscope can measure an unbinding force needed to separate the two single molecule complexes. Recent studies have shown that such unbinding force depends linearly on the logarithm of the applied loading rate, defined as a product of scanning velocity and the spring constant characterizing the investigated system (cantilever vs. surface). This dependence can be used to study the energy landscape shape of a molecular complex by the estimation of energy barrier locations and the related dissociation rates. In the present work the complex consisting of ethylene(di)aminetetraacetic acid and the bovine serum albumin was measured. The dependence between the unbinding force and the logarithm of the loading rate was linear. Using the Bell model describing the dissociation of the above molecules caused by the action of the external bond breaking force, two parameters were estimated: the dissociation rate and the position of the energy barrier needed to overcome during a transition from a bound to unbound state. The obtained results are similar to those obtained for a typical ligand--receptor interaction.

  10. 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

  11. Scalar self-interactions loosen constraints from fifth force searches

    International Nuclear Information System (INIS)

    Gubser, Steven S.; Khoury, Justin

    2004-01-01

    The mass of a scalar field mediating a fifth force is tightly constrained by experiments. We show, however, that adding a quartic self-interaction for such a scalar makes most tests much less constraining: the nonlinear equation of motion masks the coupling of the scalar to matter through the chameleon mechanism. We discuss consequences for fifth force experiments. In particular, we find that, with quartic coupling of order unity, a gravitational strength interaction with matter is allowed by current constraints. We show that our chameleon scalar field results in experimental signatures that could be detected through modest improvements of current laboratory set-ups

  12. 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

  13. Optical Near-field Interactions and Forces for Optoelectronic Devices

    Science.gov (United States)

    Kohoutek, John Michael

    Throughout history, as a particle view of the universe began to take shape, scientists began to realize that these particles were attracted to each other and hence came up with theories, both analytical and empirical in nature, to explain their interaction. The interaction pair potential (empirical) and electromagnetics (analytical) theories, both help to explain not only the interaction between the basic constituents of matter, such as atoms and molecules, but also between macroscopic objects, such as two surfaces in close proximity. The electrostatic force, optical force, and Casimir force can be categorized as such forces. A surface plasmon (SP) is a collective motion of electrons generated by light at the interface between two mediums of opposite signs of dielectric susceptibility (e.g. metal and dielectric). Recently, surface plasmon resonance (SPR) has been exploited in many areas through the use of tiny antennas that work on similar principles as radio frequency (RF) antennas in optoelectronic devices. These antennas can produce a very high gradient in the electric field thereby leading to an optical force, similar in concept to the surface forces discussed above. The Atomic Force Microscope (AFM) was introduced in the 1980s at IBM. Here we report on its uses in measuring these aforementioned forces and fields, as well as actively modulating and manipulating multiple optoelectronic devices. We have shown that it is possible to change the far field radiation pattern of an optical antenna-integrated device through modification of the near-field of the device. This modification is possible through change of the local refractive index or reflectivity of the "hot spot" of the device, either mechanically or optically. Finally, we have shown how a mechanically active device can be used to detect light with high gain and low noise at room temperature. It is the aim of several of these integrated and future devices to be used for applications in molecular sensing

  14. Distinguishing magnetic and electrostatic interactions by a Kelvin probe force microscopy–magnetic force microscopy combination

    Directory of Open Access Journals (Sweden)

    Miriam Jaafar

    2011-09-01

    Full Text Available The most outstanding feature of scanning force microscopy (SFM is its capability to detect various different short and long range interactions. In particular, magnetic force microscopy (MFM is used to characterize the domain configuration in ferromagnetic materials such as thin films grown by physical techniques or ferromagnetic nanostructures. It is a usual procedure to separate the topography and the magnetic signal by scanning at a lift distance of 25–50 nm such that the long range tip–sample interactions dominate. Nowadays, MFM is becoming a valuable technique to detect weak magnetic fields arising from low dimensional complex systems such as organic nanomagnets, superparamagnetic nanoparticles, carbon-based materials, etc. In all these cases, the magnetic nanocomponents and the substrate supporting them present quite different electronic behavior, i.e., they exhibit large surface potential differences causing heterogeneous electrostatic interaction between the tip and the sample that could be interpreted as a magnetic interaction. To distinguish clearly the origin of the tip–sample forces we propose to use a combination of Kelvin probe force microscopy (KPFM and MFM. The KPFM technique allows us to compensate in real time the electrostatic forces between the tip and the sample by minimizing the electrostatic contribution to the frequency shift signal. This is a great challenge in samples with low magnetic moment. In this work we studied an array of Co nanostructures that exhibit high electrostatic interaction with the MFM tip. Thanks to the use of the KPFM/MFM system we were able to separate the electric and magnetic interactions between the tip and the sample.

  15. Designing an experiment to measure cellular interaction forces

    Science.gov (United States)

    McAlinden, Niall; Glass, David G.; Millington, Owain R.; Wright, Amanda J.

    2013-09-01

    Optical trapping is a powerful tool in Life Science research and is becoming common place in many microscopy laboratories and facilities. The force applied by the laser beam on the trapped object can be accurately determined allowing any external forces acting on the trapped object to be deduced. We aim to design a series of experiments that use an optical trap to measure and quantify the interaction force between immune cells. In order to cause minimum perturbation to the sample we plan to directly trap T cells and remove the need to introduce exogenous beads to the sample. This poses a series of challenges and raises questions that need to be answered in order to design a set of effect end-point experiments. A typical cell is large compared to the beads normally trapped and highly non-uniform - can we reliably trap such objects and prevent them from rolling and re-orientating? In this paper we show how a spatial light modulator can produce a triple-spot trap, as opposed to a single-spot trap, giving complete control over the object's orientation and preventing it from rolling due, for example, to Brownian motion. To use an optical trap as a force transducer to measure an external force you must first have a reliably calibrated system. The optical trapping force is typically measured using either the theory of equipartition and observing the Brownian motion of the trapped object or using an escape force method, e.g. the viscous drag force method. In this paper we examine the relationship between force and displacement, as well as measuring the maximum displacement from equilibrium position before an object falls out of the trap, hence determining the conditions under which the different calibration methods should be applied.

  16. 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.

  17. 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.

  18. 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.

  19. Interactions between Rotavirus and Suwannee River Organic Matter: Aggregation, Deposition, and Adhesion Force Measurement

    KAUST Repository

    Gutierrez, Leonardo; Nguyen, Thanh H.

    2012-01-01

    M, rotavirus suspension remained stable for over 4 h. Atomic force microscopy (AFM) measurement for interaction force decay length at different ionic strengths showed that nonelectrostatic repulsive forces were mainly responsible for eliminating aggregation

  20. 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.

  1. 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.

  2. 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...

  3. Motivating forces of human actions. Neuroimaging reward and social interaction.

    Science.gov (United States)

    Walter, Henrik; Abler, Birgit; Ciaramidaro, Angela; Erk, Susanne

    2005-11-15

    In neuroeconomics, reward and social interaction are central concepts to understand what motivates human behaviour. Both concepts are investigated in humans using neuroimaging methods. In this paper, we provide an overview about these results and discuss their relevance for economic behaviour. For reward it has been shown that a system exists in humans that is involved in predicting rewards and thus guides behaviour, involving a circuit including the striatum, the orbitofrontal cortex and the amygdala. Recent studies on social interaction revealed a mentalizing system representing the mental states of others. A central part of this system is the medial prefrontal cortex, in particular the anterior paracingulate cortex. The reward as well as the mentalizing system is engaged in economic decision-making. We will discuss implications of this study for neuromarketing as well as general implications of these results that may help to provide deeper insights into the motivating forces of human behaviour.

  4. Parallel force assay for protein-protein interactions.

    Science.gov (United States)

    Aschenbrenner, Daniela; Pippig, Diana A; Klamecka, Kamila; Limmer, Katja; Leonhardt, Heinrich; Gaub, Hermann E

    2014-01-01

    Quantitative proteome research is greatly promoted by high-resolution parallel format assays. A characterization of protein complexes based on binding forces offers an unparalleled dynamic range and allows for the effective discrimination of non-specific interactions. Here we present a DNA-based Molecular Force Assay to quantify protein-protein interactions, namely the bond between different variants of GFP and GFP-binding nanobodies. We present different strategies to adjust the maximum sensitivity window of the assay by influencing the binding strength of the DNA reference duplexes. The binding of the nanobody Enhancer to the different GFP constructs is compared at high sensitivity of the assay. Whereas the binding strength to wild type and enhanced GFP are equal within experimental error, stronger binding to superfolder GFP is observed. This difference in binding strength is attributed to alterations in the amino acids that form contacts according to the crystal structure of the initial wild type GFP-Enhancer complex. Moreover, we outline the potential for large-scale parallelization of the assay.

  5. Parallel force assay for protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Daniela Aschenbrenner

    Full Text Available Quantitative proteome research is greatly promoted by high-resolution parallel format assays. A characterization of protein complexes based on binding forces offers an unparalleled dynamic range and allows for the effective discrimination of non-specific interactions. Here we present a DNA-based Molecular Force Assay to quantify protein-protein interactions, namely the bond between different variants of GFP and GFP-binding nanobodies. We present different strategies to adjust the maximum sensitivity window of the assay by influencing the binding strength of the DNA reference duplexes. The binding of the nanobody Enhancer to the different GFP constructs is compared at high sensitivity of the assay. Whereas the binding strength to wild type and enhanced GFP are equal within experimental error, stronger binding to superfolder GFP is observed. This difference in binding strength is attributed to alterations in the amino acids that form contacts according to the crystal structure of the initial wild type GFP-Enhancer complex. Moreover, we outline the potential for large-scale parallelization of the assay.

  6. Driving force for hydrophobic interaction at different length scales.

    Science.gov (United States)

    Zangi, Ronen

    2011-03-17

    We study by molecular dynamics simulations the driving force for the hydrophobic interaction between graphene sheets of different sizes down to the atomic scale. Similar to the prediction by Lum, Chandler, and Weeks for hard-sphere solvation [J. Phys. Chem. B 1999, 103, 4570-4577], we find the driving force to be length-scale dependent, despite the fact that our model systems do not exhibit dewetting. For small hydrophobic solutes, the association is purely entropic, while enthalpy favors dissociation. The latter is demonstrated to arise from the enhancement of hydrogen bonding between the water molecules around small hydrophobes. On the other hand, the attraction between large graphene sheets is dominated by enthalpy which mainly originates from direct solute-solute interactions. The crossover length is found to be inside the range of 0.3-1.5 nm(2) of the surface area of the hydrophobe that is eliminated in the association process. In the large-scale regime, different thermodynamic properties are scalable with this change of surface area. In particular, upon dimerization, a total and a water-induced stabilization of approximately 65 and 12 kJ/mol/nm(2) are obtained, respectively, and on average around one hydrogen bond is gained per 1 nm(2) of graphene sheet association. Furthermore, the potential of mean force between the sheets is also scalable except for interplate distances smaller than 0.64 nm which corresponds to the region around the barrier for removing the last layer of water. It turns out that, as the surface area increases, the relative height of the barrier for association decreases and the range of attraction increases. It is also shown that, around small hydrophobic solutes, the lifetime of the hydrogen bonds is longer than in the bulk, while around large hydrophobes it is the same. Nevertheless, the rearrangement of the hydrogen-bond network for both length-scale regimes is slower than in bulk water. © 2011 American Chemical Society

  7. The effect of force feedback delay on stiffness perception and grip force modulation during tool-mediated interaction with elastic force fields.

    Science.gov (United States)

    Leib, Raz; Karniel, Amir; Nisky, Ilana

    2015-05-01

    During interaction with objects, we form an internal representation of their mechanical properties. This representation is used for perception and for guiding actions, such as in precision grip, where grip force is modulated with the predicted load forces. In this study, we explored the relationship between grip force adjustment and perception of stiffness during interaction with linear elastic force fields. In a forced-choice paradigm, participants probed pairs of virtual force fields while grasping a force sensor that was attached to a haptic device. For each pair, they were asked which field had higher level of stiffness. In half of the pairs, the force feedback of one of the fields was delayed. Participants underestimated the stiffness of the delayed field relatively to the nondelayed, but their grip force characteristics were similar in both conditions. We analyzed the magnitude of the grip force and the lag between the grip force and the load force in the exploratory probing movements within each trial. Right before answering which force field had higher level of stiffness, both magnitude and lag were similar between delayed and nondelayed force fields. These results suggest that an accurate internal representation of environment stiffness and time delay was used for adjusting the grip force. However, this representation did not help in eliminating the bias in stiffness perception. We argue that during performance of a perceptual task that is based on proprioceptive feedback, separate neural mechanisms are responsible for perception and action-related computations in the brain. Copyright © 2015 the American Physiological Society.

  8. Soft matter interactions at the molecular scale: interaction forces and energies between single hydrophobic model peptides.

    Science.gov (United States)

    Stock, Philipp; Utzig, Thomas; Valtiner, Markus

    2017-02-08

    In all realms of soft matter research a fundamental understanding of the structure/property relationships based on molecular interactions is crucial for developing a framework for the targeted design of soft materials. However, a molecular picture is often difficult to ascertain and yet essential for understanding the many different competing interactions at play, including entropies and cooperativities, hydration effects, and the enormous design space of soft matter. Here, we characterized for the first time the interaction between single hydrophobic molecules quantitatively using atomic force microscopy, and demonstrated that single molecular hydrophobic interaction free energies are dominated by the area of the smallest interacting hydrophobe. The interaction free energy amounts to 3-4 kT per hydrophobic unit. Also, we find that the transition state of the hydrophobic interactions is located at 3 Å with respect to the ground state, based on Bell-Evans theory. Our results provide a new path for understanding the nature of hydrophobic interactions at the single molecular scale. Our approach enables us to systematically vary hydrophobic and any other interaction type by utilizing peptide chemistry providing a strategic advancement to unravel molecular surface and soft matter interactions at the single molecular scale.

  9. Unlocking higher harmonics in atomic force microscopy with gentle interactions.

    Science.gov (United States)

    Santos, Sergio; Barcons, Victor; Font, Josep; Verdaguer, Albert

    2014-01-01

    In dynamic atomic force microscopy, nanoscale properties are encoded in the higher harmonics. Nevertheless, when gentle interactions and minimal invasiveness are required, these harmonics are typically undetectable. Here, we propose to externally drive an arbitrary number of exact higher harmonics above the noise level. In this way, multiple contrast channels that are sensitive to compositional variations are made accessible. Numerical integration of the equation of motion shows that the external introduction of exact harmonic frequencies does not compromise the fundamental frequency. Thermal fluctuations are also considered within the detection bandwidth of interest and discussed in terms of higher-harmonic phase contrast in the presence and absence of an external excitation of higher harmonics. Higher harmonic phase shifts further provide the means to directly decouple the true topography from that induced by compositional heterogeneity.

  10. Autogenic and Allogenic: Emergent Coastline Patterns Interact With Forcing Variations

    Science.gov (United States)

    Murray, A. B.; Alvarez Antolinez, J. A.; Mendez, F. J.; Moore, L. J.; Wood, J.; Farley, G.

    2017-12-01

    A range of coastline shapes can emerge from large-scale morphodynamic interactions. Coastline shape determines local wave influences. Local wave influences (fluxes of alongshore momentum), determine sediment fluxes, and gradients in these sediment fluxes, in turn, alter coastline shape. Modeling studies show that such feedbacks lead to an instability, and to subsequent finite-amplitude interactions, producing self-organized patterns and emergent structures including sandwaves, capes, and spits (e.g. Ashton and Murray, 2006; Ashton et al., 2015); spiral bays on rocky coastlines (e.g. Barkwith et al., 2014); and convex, spit-bounded coastlines (Ells et al., in prep.). Coastline shapes depend sensitively on wave climate, defined as the angular distribution of wave influences on alongshore sediment transport. Therefore, shifts in wave climate arising from shifts in storms (decadal scale fluctuations or longer-term trends) will tend to change coastline shape. Previous efforts have detected changing coastline shape, likely related to changing influence from hurricane-generated waves, as expressed in changes in the location and intensity of coastal erosion zones along the cuspate capes in North Carolina, USA (Moore et al., 2013). These efforts involved the assumption that coastline response to changing forcing occurs in a quasi-equilibrium manner. However, in some cases coastline responses can exhibit long-term memory and path dependence (Thomas et al., 2016). Recently, we have hindcast the wave climate affecting the North Carolina coast since 1870, using a series of statistical analyses to downscale from basin-scale surface pressure fields to regional deep-water wave climate, and then a numerical transformation to local offshore wave climate. We used this wave climate as input for the Coastline Evolution Model (CEM). The results show that the emergent coastline features respond to decadal-scale shifts in wave climate, but with time lags that complicate the relationship

  11. 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...

  12. 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.

  13. 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

  14. Exact expressions for colloidal plane-particle interaction forces and energies with applications to atomic force microscopy

    International Nuclear Information System (INIS)

    Zypman, F R

    2006-01-01

    We begin by deriving a general useful theoretical relationship between the plane-particle interaction forces in solution, and the corresponding plane-plane interaction energies. This is the main result of the paper. It provides a simple tool to obtain closed-form particle-plane forces from knowledge of plane-plane interaction energies. To illustrate the simplicity of use of this general formalism, we apply it to find particle-plane interactions within the Derjaguin-Landau-Verwey-Overbeek (DLVO) framework. Specifically, we obtain analytical expressions for forces and interaction energies in the van der Waals and the electrical double layer cases. The van der Waals expression is calculated here for benchmarking purposes and is compared with well-established expressions from Hamaker theory. The interactions for the electric double layer situation are computed in two cases: the linear superposition approximation and the constant surface potential. In both cases, our closed-form expressions were compared with existent numerical results. We also use the main result of this paper to generate an analytical force-separation expression based on atomic force microscope experiments for a tip and surface immersed in an aqueous solution, and compare it with the corresponding numerical results. Finally, based on our main result, we generalize the Derjaguin approximation by calculating the next order of approximation, thus obtaining a formula valuable for colloidal interaction estimations

  15. Polarization phenomena of nuclear force and weak interaction

    International Nuclear Information System (INIS)

    Konuma, Michitsugu

    1982-01-01

    As one of the projects at the National Laboratory of High Energy Physics (KEK), the measurement of parity non-conservation component in nuclear force was proposed. The theoretical survey of this proposal is reported. The non-relativistic parity non-conserving potential between nucleons can be obtained from the interaction between a quark and a gauge boson. The wave function of a nucleus, which includes the inverse components of the parity, can be written. A practical experiment was designed. The mixing of the inverse components and the interference of an inverse component in the 1042 keV and 1081 keV levels of F 18 may produce the parity non-conservation. The processes which suggest the existence of parity non-conservation were studied. The processes are the circular polarization of gamma-ray emitted from a nucleus, the angular distribution of gamma-ray emitted from polarized nuclei, the collision of the proton beam with helicity of plus and minus on other nuclei, the spin rotation of neutrons, and the alpha decay of the parity non-conservation. The preliminary results of the experiment on the effects of parity non-conservation in the collision process of polarized proton beam have been reported, and the theoretical analyses were performed. The violation of parity conservation in large momentum collision is discussed. The comparison of the theoretical results with the experimental ones is presented. (Kato, T.)

  16. Force interaction and 3D pole movement in double poling.

    Science.gov (United States)

    Stöggl, T; Holmberg, H-C

    2011-12-01

    The aim of this study was to analyze double poling using combined kinetic and 3D kinematic analysis at high skiing speeds as regards pole force components, pole angles and pole behavior during the poling and swing phase. The hypothesis was that a horizontal pole force is more predictive for maximal skiing speed (V(max)) than the resultant pole force. Sixteen elite skiers performed a double-poling V(max) test while treadmill roller skiing. Pole forces and 3D kinematics of pole movement at a speed of 30 km/h were analyzed and related to V(max). The duration of the "preparation phase" showed the strongest relationship with V(max) (r=0.87, Pmax) compared with the resultant pole force. Impact force was not related to V(max). At high skiing speeds, skiers should aim to combine high pole forces with appropriate timing of pole forces and appropriate pole and body positions during the swing and poling phase. The emphasis in training should be on the development of specific strength capacities for pole force production and the utilization of these capacities in double-poling training sessions. © 2011 John Wiley & Sons A/S.

  17. 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.

  18. Long range forces and limits on unparticle interactions

    International Nuclear Information System (INIS)

    Deshpande, N.G.; Hsu, Stephen D.H.; Jiang Jing

    2008-01-01

    Couplings between standard model particles and unparticles from a nontrivial scale invariant sector can lead to long range forces. If the forces couple to quantities such as baryon or lepton (electron) number, stringent limits result from tests of the gravitational inverse square law. These limits are much stronger than from collider phenomenology and astrophysics

  19. Stochastic motion from a forced plasma-maser interaction

    International Nuclear Information System (INIS)

    Honjo, Haruo; Nambu, Mitsuhiro

    1986-01-01

    A model of forced plasma-maser effects is examined numerically. The model represents a conservative system and reduces to the forced type of the original Lotka-Volterra equation. A stochastic motion is found to occur when the density of a cold ion beam becomes larger. (author)

  20. Interactive forces between lignin and cellulase as determined by atomic force microscopy

    OpenAIRE

    Qin, Chengrong; Clarke, Kimberley; Li, Kecheng

    2014-01-01

    Background Lignin is a complex polymer which inhibits the enzymatic conversion of cellulose to glucose in lignocellulose biomass for biofuel production. Cellulase enzymes irreversibly bind to lignin, deactivating the enzyme and lowering the overall activity of the hydrolyzing reaction solution. Within this study, atomic force microscopy (AFM) is used to compare the adhesion forces between cellulase and lignin with the forces between cellulase and cellulose, and to study the moiety groups invo...

  1. Investigation of specific interactions between T7 promoter and T7 RNA polymerase by force spectroscopy using atomic force microscope.

    Science.gov (United States)

    Zhang, Xiaojuan; Yao, Zhixuan; Duan, Yanting; Zhang, Xiaomei; Shi, Jinsong; Xu, Zhenghong

    2018-01-11

    The specific recognition and binding of promoter and RNA polymerase is the first step of transcription initiation in bacteria and largely determines transcription activity. Therefore, direct analysis of the interaction between promoter and RNA polymerase in vitro may be a new strategy for promoter characterization, to avoid interference due to the cell's biophysical condition and other regulatory elements. In the present study, the specific interaction between T7 promoter and T7 RNA polymerase was studied as a model system using force spectroscopy based on atomic force microscope (AFM). The specific interaction between T7 promoter and T7 RNA polymerase was verified by control experiments, and the rupture force in this system was measured as 307.2 ± 6.7 pN. The binding between T7 promoter mutants with various promoter activities and T7 RNA polymerase was analyzed. Interaction information including rupture force, rupture distance and binding percentage were obtained in vitro , and reporter gene expression regulated by these promoters was also measured according to a traditional promoter activity characterization method in vivo Using correlation analysis, it was found that the promoter strength characterized by reporter gene expression was closely correlated with rupture force and the binding percentage by force spectroscopy. These results indicated that the analysis of the interaction between promoter and RNA polymerase using AFM-based force spectroscopy was an effective and valid approach for the quantitative characterization of promoters. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  2. Magnetostatic interactions and forces between cylindrical permanent magnets

    International Nuclear Information System (INIS)

    Vokoun, David; Beleggia, Marco; Heller, Ludek; Sittner, Petr

    2009-01-01

    Permanent magnets of various shapes are often utilized in magnetic actuators, sensors or releasable magnetic fasteners. Knowledge of the magnetic force is required to control devices reliably. Here, we introduce an analytical expression for calculating the attraction force between two cylindrical permanent magnets on the assumption of uniform magnetization. Although the assumption is not fulfilled exactly in cylindrical magnets, we obtain a very good agreement between the calculated and measured forces between two identical cylindrical magnets and within an array of NdFeB cylindrical magnets.

  3. Balancing the Interactions of Ions, Water, and DNA in the Drude Polarizable Force Field

    OpenAIRE

    Savelyev, Alexey; MacKerell, Alexander D.

    2014-01-01

    Recently we presented a first-generation all-atom Drude polarizable force field for DNA based on the classical Drude oscillator model, focusing on optimization of key dihedral angles followed by extensive validation of the force field parameters. Presently, we describe the procedure for balancing the electrostatic interactions between ions, water, and DNA as required for development of the Drude force field for DNA. The proper balance of these interactions is shown to impact DNA stability and...

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Reverse engineering of an affinity-switchable molecular interaction characterized by atomic force microscopy single-molecule force spectroscopy.

    Science.gov (United States)

    Anselmetti, Dario; Bartels, Frank Wilco; Becker, Anke; Decker, Björn; Eckel, Rainer; McIntosh, Matthew; Mattay, Jochen; Plattner, Patrik; Ros, Robert; Schäfer, Christian; Sewald, Norbert

    2008-02-19

    Tunable and switchable interaction between molecules is a key for regulation and control of cellular processes. The translation of the underlying physicochemical principles to synthetic and switchable functional entities and molecules that can mimic the corresponding molecular functions is called reverse molecular engineering. We quantitatively investigated autoinducer-regulated DNA-protein interaction in bacterial gene regulation processes with single atomic force microscopy (AFM) molecule force spectroscopy in vitro, and developed an artificial bistable molecular host-guest system that can be controlled and regulated by external signals (UV light exposure and thermal energy). The intermolecular binding functionality (affinity) and its reproducible and reversible switching has been proven by AFM force spectroscopy at the single-molecule level. This affinity-tunable optomechanical switch will allow novel applications with respect to molecular manipulation, nanoscale rewritable molecular memories, and/or artificial ion channels, which will serve for the controlled transport and release of ions and neutral compounds in the future.

  9. 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.

  10. 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

  11. Magnetostatic interactions and forces between cylindrical permanent magnets

    Czech Academy of Sciences Publication Activity Database

    Vokoun, David; Beleggia, M.; Heller, Luděk; Šittner, Petr

    2009-01-01

    Roč. 321, č. 22 (2009), s. 3758-3763 ISSN 0304-8853 EU Projects: European Commission(XE) 46559 - CERINKA Institutional research plan: CEZ:AV0Z10100520 Keywords : cylinder * force measurement * magnetostatic * permanent magnet Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.204, year: 2009

  12. 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.

  13. 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.

  14. 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.

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

    Science.gov (United States)

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

    2015-06-01

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

  16. Interface bonding in silicon oxide nanocontacts: interaction potentials and force measurements

    Science.gov (United States)

    Wierez-Kien, M.; Craciun, A. D.; Pinon, A. V.; Le Roux, S.; Gallani, J. L.; Rastei, M. V.

    2018-04-01

    The interface bonding between two silicon-oxide nanoscale surfaces has been studied as a function of atomic nature and size of contacting asperities. The binding forces obtained using various interaction potentials are compared with experimental force curves measured in vacuum with an atomic force microscope. In the limit of small nanocontacts (typically contact area which is altered by stretching speeds. The mean unbinding force is found to decrease as the contact spends time in the attractive regime. This contact weakening is featured by a negative aging coefficient which broadens and shifts the thermal-induced force distribution at low stretching speeds.

  17. The Röntgen interaction and forces on dipoles in time-modulated optical fields

    Science.gov (United States)

    Sonnleitner, Matthias; Barnett, Stephen M.

    2017-12-01

    The Röntgen term is an often neglected contribution to the interaction between an atom and an electromagnetic field in the electric dipole approximation. In this work we discuss how this interaction term leads to a difference between the kinetic and canonical momentum of an atom which, in turn, leads to surprising radiation forces acting on the atom. We use a number of examples to explore the main features of this interaction, namely forces acting against the expected dipole force or accelerations perpendicular to the beam propagation axis.

  18. Converting biomolecular modelling data based on an XML representation.

    Science.gov (United States)

    Sun, Yudong; McKeever, Steve

    2008-08-25

    Biomolecular modelling has provided computational simulation based methods for investigating biological processes from quantum chemical to cellular levels. Modelling such microscopic processes requires atomic description of a biological system and conducts in fine timesteps. Consequently the simulations are extremely computationally demanding. To tackle this limitation, different biomolecular models have to be integrated in order to achieve high-performance simulations. The integration of diverse biomolecular models needs to convert molecular data between different data representations of different models. This data conversion is often non-trivial, requires extensive human input and is inevitably error prone. In this paper we present an automated data conversion method for biomolecular simulations between molecular dynamics and quantum mechanics/molecular mechanics models. Our approach is developed around an XML data representation called BioSimML (Biomolecular Simulation Markup Language). BioSimML provides a domain specific data representation for biomolecular modelling which can effciently support data interoperability between different biomolecular simulation models and data formats.

  19. Experimental study on the control interaction force coefficient; Soju ryutairyoku kansho keisu ni kansuru jikkenteki kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Nakatake, K; Oda, K; Yoshitake, A; Fujita, K; Nakajima, A [Kyushu University, Fukuoka (Japan). Faculty of Engineering

    1996-04-10

    The interaction force induced to hull by steering is important for prediction of control performance of ships. The control interaction force coefficient dependent on the steering has been investigated through the rudder angle tests using three small model ships with a length of 2.5 m, i.e., mathematical type of ship, cargo type of ship, and tanker type of ship. The interaction forces acting on the hull, propeller, and rudder were determined by measuring the lateral force as well as the forward force of the hydrodynamic forces acting on the rudder. These forces were compared with the theoretically calculated values. Prior to the rudder angle tests, the self propulsion factor and the number of revolution of propeller were determined from the results of the open water tests, resistance tests, and self propulsion tests by the changing load method. The rudder angle tests were conducted under this number of revolution of propeller as a standard condition, and under those increasing and decreasing by 15%. Consequently, the interaction forces determined from the rudder angle tests agreed well with those determined from the other tests. When comparing the control hydrodynamic forces determined from the tests with those theoretically calculated, a similar trend was observed. Effectiveness of the theoretical model was confirmed. 4 refs., 14 figs., 3 tabs.

  20. PREFACE: Radiation Damage in Biomolecular Systems (RADAM07)

    Science.gov (United States)

    McGuigan, Kevin G.

    2008-03-01

    The annual meeting of the COST P9 Action `Radiation damage in biomolecular systems' took place from 19-22 June 2007 in the Royal College of Surgeons in Ireland, in Dublin. The conference was structured into 5 Working Group sessions: Electrons and biomolecular interactions Ions and biomolecular interactions Radiation in physiological environments Theoretical developments for radiation damage Track structure in cells Each of the five working groups presented two sessions of invited talks. Professor Ron Chesser of Texas Tech University, USA gave a riveting plenary talk on `Mechanisms of Adaptive Radiation Responses in Mammals at Chernobyl' and the implications his work has on the Linear-No Threshold model of radiation damage. In addition, this was the first RADAM meeting to take place after the Alexander Litvenenko affair and we were fortunate to have one of the leading scientists involved in the European response Professor Herwig Paretzke of GSF-Institut für Strahlenschutz, Neuherberg, Germany, available to speak. The remaining contributions were presented in the poster session. A total of 72 scientific contributions (32 oral, 40 poster), presented by 97 participants from 22 different countries, gave an overview on the current progress in the 5 different subfields. A 1-day pre-conference `Early Researcher Tutorial Workshop' on the same topic kicked off on 19 June attended by more than 40 postgrads, postdocs and senior researchers. Twenty papers, based on these reports, are included in this volume of Journal of Physics: Conference Series. All the contributions in this volume were fully refereed, and they represent a sample of the courses, invited talks and contributed talks presented during RADAM07. The interdisciplinary RADAM07 conference brought together researchers from a variety of different fields with a common interest in biomolecular radiation damage. This is reflected by the disparate backgrounds of the authors of the papers presented in these proceedings

  1. Resonant Optical Gradient Force Interaction for Nano-Imaging and-Spectroscopy

    Science.gov (United States)

    2016-07-19

    New J. Phys. 18 (2016) 053042 doi:10.1088/1367-2630/18/5/053042 PAPER Resonant optical gradient force interaction for nano-imaging and -spectroscopy...HonghuaUYang andMarkus BRaschke Department of Physics , Department of Chemistry, and JILA,University of Colorado, Boulder, CO80309,USA E-mail...honghua.yang@colorado.edu andmarkus.raschke@colorado.edu Keywords:nano spectroscopy, optical force, near-field optics Abstract The optical gradient force

  2. UMER: An analog computer for dynamics of swarms interacting via long-range forces

    International Nuclear Information System (INIS)

    Kishek, R.A.; Bai, G.; Bernal, S.; Feldman, D.; Godlove, T.F.; Haber, I.; O'Shea, P.G.; Quinn, B.; Papadopoulos, C.; Reiser, M.; Stratakis, D.; Tian, K.; Tobin, C.J.; Walter, M.

    2006-01-01

    Some of the most challenging and interesting problems in nature involve large numbers of objects or particles mutually interacting through long-range forces. Examples range from galaxies and plasmas to flocks of birds and traffic flow on a highway. Even in cases where the form of the interacting force is precisely known, such as the 1/r 2 -dependent Coulomb and gravitational forces, such problems present a formidable theoretical and modeling challenge for large numbers of interacting bodies. This paper reports on a newly constructed, scaled particle accelerator that will serve as an experimental testbed for the dynamics of swarms interacting through long-range forces. Primarily designed for intense beam dynamics studies for advanced accelerators, the University of Maryland Electron Ring (UMER) design is described in detail and an update on commissioning is provided. An example application to a system other than a charged particle beam is discussed

  3. The Use of Force Notation to Detect Students' Misconceptions: Mutual Interactions Case

    Science.gov (United States)

    Serhane, Ahcene; Zeghdaoui, Abdelhamid; Debiache, Mehdi

    2017-01-01

    Using a conventional notation for representing forces on diagrams, students were presented with questions on the interaction between two objects. The results show that complete understanding of Newton's Third Law of Motion is quite rare, and that some problems relate to misunderstanding which force acts on each body. The use of the terms…

  4. Normal and friction stabilization techniques for interactive rigid body constraint-based contact force computations

    DEFF Research Database (Denmark)

    Silcowitz-Hansen, Morten; Abel, Sarah Maria Niebe; Erleben, Kenny

    2010-01-01

    We present a novel, yet simple, method for stabilization of normal forces. A normal stabilization term, carefully designed from hypotheses about interactive usability, is added to the contact force problem. Further, we propose friction stabilization as a completely new stabilization paradigm...

  5. Predicting wind farm wake interaction with RANS: an investigation of the Coriolis force

    DEFF Research Database (Denmark)

    van der Laan, Paul; Hansen, Kurt Schaldemose; Sørensen, Niels N.

    2015-01-01

    A Reynolds-averaged Navier-Stokes code is used to simulate the interaction of two neighboring wind farms. The influence of the Coriolis force is investigated by modeling the atmospheric surface/boundary layer with three different methodologies. The results show that the Coriolis force is negligible...

  6. Ion induced fragmentation of biomolecular systems at low collision energies

    International Nuclear Information System (INIS)

    Bernigaud, V; Adoui, L; Chesnel, J Y; Rangama, J; Huber, B A; Manil, B; Alvarado, F; Bari, S; Hoekstra, R; Postma, J; Schlathoelter, T

    2009-01-01

    In this paper, we present results of different collision experiments between multiply charged ions at low collision energies (in the keV-region) and biomolecular systems. This kind of interaction allows to remove electrons form the biomolecule without transferring a large amount of vibrational excitation energy. Nevertheless, following the ionization of the target, fragmentation of biomolecular species may occur. It is the main objective of this work to study the physical processes involved in the dissociation of highly electronically excited systems. In order to elucidate the intrinsic properties of certain biomolecules (porphyrins and amino acids) we have performed experiments in the gas phase with isolated systems. The obtained results demonstrate the high stability of porphyrins after electron removal. Furthermore, a dependence of the fragmentation pattern produced by multiply charged ions on the isomeric structure of the alanine molecule has been shown. By considering the presence of other surrounding biomolecules (clusters of nucleobases), a strong influence of the environment of the biomolecule on the fragmentation channels and their modification, has been clearly proven. This result is explained, in the thymine and uracil case, by the formation of hydrogen bonds between O and H atoms, which is known to favor planar cluster geometries.

  7. Regimes of seasonal air-sea interaction and implications for performance of forced simulations

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Renguang [Center for Ocean-Land-Atmosphere Studies, Calverton, MD (United States); Kirtman, Ben P. [Center for Ocean-Land-Atmosphere Studies, Calverton, MD (United States); George Mason University, School of Computational Sciences, Fairfax, VA (United States)

    2007-09-15

    Sea surface temperature (SST) anomalies can induce anomalous convection through surface evaporation and low-level moisture convergence. This SST forcing of the atmosphere is indicated in a positive local rainfall-SST correlation. Anomalous convection can feedback on SST through cloud-radiation and wind-evaporation effects and wind-induced oceanic mixing and upwelling. These atmospheric feedbacks are reflected in a negative local rainfall-SST tendency correlation. As such, the simultaneous rainfall-SST and rainfall-SST tendency correlations can indicate the nature of local air-sea interactions. Based on the magnitude of simultaneous rainfall-SST and rainfall-SST tendency correlations, the present study identifies three distinct regimes of local air-sea interactions. The relative importance of SST forcing and atmospheric forcing differs in these regimes. In the equatorial central-eastern Pacific and, to a smaller degree, in the western equatorial Indian Ocean, SST forcing dominates throughout the year and the surface heat flux acts mainly as a damping term. In the tropical Indo-western Pacific Ocean regions, SST forcing and atmospheric forcing dominate alternatively in different seasons. Atmospheric forcing dominates in the local warm/rainy season. SST forcing dominates with a positive wind-evaporation feedback during the transition to the cold/dry season. SST forcing also dominates during the transition to the warm/rainy season but with a negative cloud-radiation feedback. The performance of atmospheric general circulation model simulations forced by observed SST is closely linked to the regime of air-sea interaction. The forced simulations have good performance when SST forcing dominates. The performance is low or poor when atmospheric forcing dominates. (orig.)

  8. Interacting trophic forcing and the population dynamics of herring

    DEFF Research Database (Denmark)

    Lindegren, Martin; Ostman, Orjan; Gardmark, Anna

    2011-01-01

    -up nor top-down, but rather through multiple external and internal drivers. While in many studies single drivers have been identified, potential synergies of multiple factors, as well as their relative importance in regulating population dynamics of small pelagic fish, is a largely unresolved issue....... Using a statistical, age-structured modeling approach, we demonstrate the relative importance and influence of bottom-up (e.g., climate, zooplankton availability) and top-down (i.e., fishing and predation) factors on the population dynamics of Bothnian Sea herring (Clupea harengus) throughout its life...... cycle. Our results indicate significant bottom-up effects of zooplankton and interspecific competition from sprat (Sprattus sprattus), particularly on younger age classes of herring. Although top-down forcing through fishing and predation by grey seals (Halichoerus grypus) and Atlantic cod (Gadus morhua...

  9. Intersegmental interactions in supercoiled DNA: atomic force microscope study

    Energy Technology Data Exchange (ETDEWEB)

    Shlyakhtenko, Luda S.; Miloseska, Lela; Potaman, Vladimir N.; Sinden, Richard R.; Lyubchenko, Yuri L

    2003-10-15

    Intersegmental interactions in DNA facilitated by the neutralization of electrostatic repulsion was studied as a function of salt concentration and DNA supercoiling. DNA samples with defined superhelical densities were deposited onto aminopropyl mica at different ionic conditions and imaged in air after drying of the samples. Similar to hydrodynamic data, we did not observe a collapse of supercoiled DNA, as proposed earlier by cryo-EM studies. Instead, the formation of the contacts between DNA helices within supercoiled loops with no visible space between the duplexes was observed. The length of such close contacts increased upon increasing NaCl concentration. DNA supercoiling was a critical factor for the stabilization of intersegmental contacts. Implications of the observed effect for understanding DNA compaction in the cell and for regulation DNA transactions via interaction of distantly separated DNA regions are discussed.

  10. Interaction of two walkers: wave-mediated energy and force.

    Science.gov (United States)

    Borghesi, Christian; Moukhtar, Julien; Labousse, Matthieu; Eddi, Antonin; Fort, Emmanuel; Couder, Yves

    2014-12-01

    A bouncing droplet, self-propelled by its interaction with the waves it generates, forms a classical wave-particle association called a "walker." Previous works have demonstrated that the dynamics of a single walker is driven by its global surface wave field that retains information on its past trajectory. Here we investigate the energy stored in this wave field for two coupled walkers and how it conveys an interaction between them. For this purpose, we characterize experimentally the "promenade modes" where two walkers are bound and propagate together. Their possible binding distances take discrete values, and the velocity of the pair depends on their mutual binding. The mean parallel motion can be either rectilinear or oscillating. The experimental results are recovered analytically with a simple theoretical framework. A relation between the kinetic energy of the droplets and the total energy of the standing waves is established.

  11. Baryon interactions from lattice QCD with physical quark masses - Nuclear forces and ΞΞ forces -

    Science.gov (United States)

    Doi, Takumi; Iritani, Takumi; Aoki, Sinya; Gongyo, Shinya; Hatsuda, Tetsuo; Ikeda, Yoichi; Inoue, Takashi; Ishii, Noriyoshi; Miyamoto, Takaya; Nemura, Hidekatsu; Sasaki, Kenji

    2018-03-01

    We present the latest lattice QCD results for baryon interactions obtained at nearly physical quark masses. Nf = 2 + 1 nonperturbatively O(a)-improved Wilson quark action with stout smearing and Iwasaki gauge action are employed on the lattice of (96a)4 ≃(8.1fm)4 with a-1 ≃2.3 GeV, where mπ ≃146 MeV and mK ≃525 MeV. In this report, we study the two-nucleon systems and two-Ξ systems in 1S0 channel and 3S1-3D1 coupled channel, and extract central and tensor interactions by the HAL QCD method. We also present the results for the NΩ interaction in 5S2 channel which is relevant to the NΩ pair-momentum correlation in heavy-ion collision experiments.

  12. 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.

  13. 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.

  14. Heat, mass and force flows in supersonic shockwave interaction

    Science.gov (United States)

    Dixon, John Michael

    There is no cost effective way to deliver a payload to space and, with rising fuel prices, currently the price to travel commercially is also becoming more prohibitive to the public. During supersonic flight, compressive shock waves form around the craft which could be harnessed to deliver an additional lift on the craft. Using a series of hanging plates below a lifting wing design, the total lift generated can be increased above conventional values, while still maintaining a similar lift-to-drag ratio. Here, we study some of the flows involved in supersonic shockwave interaction. This analysis uses ANSYS Fluent Computational Fluid Dynamics package as the modeler. Our findings conclude an increase of up to 30% lift on the modeled craft while maintaining the lift-to-drag profile of the unmodified lifting wing. The increase in lift when utilizing the shockwave interaction could increase transport weight and reduce fuel cost for space and commercial flight, as well as mitigating negative effects associated with supersonic travel.

  15. Using optical tweezers for measuring the interaction forces between human bone cells and implant surfaces: System design and force calibration

    International Nuclear Information System (INIS)

    Andersson, Martin; Madgavkar, Ashwin; Stjerndahl, Maria; Wu, Yanrong; Tan, Weihong; Duran, Randy; Niehren, Stefan; Mustafa, Kamal; Arvidson, Kristina; Wennerberg, Ann

    2007-01-01

    Optical tweezers were used to study the interaction and attachment of human bone cells to various types of medical implant materials. Ideally, the implant should facilitate cell attachment and promote migration of the progenitor cells in order to decrease the healing time. It is therefore of interest, in a controlled manner, to be able to monitor the cell adhesion process. Results from such studies would help foresee the clinical outcome of integrating medical implants. The interactions between two primary cell culture models, human gingival fibroblasts and bone forming human osteoblast cells, and three different implant materials, glass, titanium, and hydroxyapatite, were studied. A novel type of optical tweezers, which has a newly designed quadrant detector and a powerful 3 W laser was constructed and force calibrated using two different methods: one method in which the stiffness of the optical trap was obtained by monitoring the phase lag between the trap and the moved object when imposing a forced oscillation on the trapped object and another method in which the maximum trapping force was derived from the critical velocity at which the object escapes the trap. Polystyrene beads as well as cells were utilized for the calibrations. This is the first time that cells have been used directly for these types of force calibrations and, hence, direct measurements of forces exerted on cells can be performed, thus avoiding the difficulties often encountered when translating the results obtained from cell measurements to the calibrations obtained with reference materials. This more straightforward approach represents an advantage in comparison to established methods

  16. Students' Understanding on Newton's Third Law in Identifying the Reaction Force in Gravity Interactions

    Science.gov (United States)

    Zhou, Shaona; Zhang, Chunbin; Xiao, Hua

    2015-01-01

    In the past three decades, previous researches showed that students had various misconceptions of Newton's Third Law. The present study focused on students' difficulties in identifying the third-law force pair in gravity interaction situations. An instrument involving contexts with gravity and non-gravity associated interactions was designed and…

  17. Contact angles in thin liquid films III. Interaction forces in Newton black soap films

    NARCIS (Netherlands)

    Feijter, J.A. de; Vrij, A.

    The interaction parameters of Newton black soap films stabilized by NaDS, as derived from contact angle experiments, have been interpretated in terms of the structure and the interaction forces in the films. From the film thickness and the difference between the surface excess of the salt in the

  18. 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.

  19. Validation of Multibody Program to Optimize Simulated Trajectories II Parachute Simulation with Interacting Forces

    Science.gov (United States)

    Raiszadeh, Behzad; Queen, Eric M.; Hotchko, Nathaniel J.

    2009-01-01

    A capability to simulate trajectories of multiple interacting rigid bodies has been developed, tested and validated. This capability uses the Program to Optimize Simulated Trajectories II (POST 2). The standard version of POST 2 allows trajectory simulation of multiple bodies without force interaction. In the current implementation, the force interaction between the parachute and the suspended bodies has been modeled using flexible lines, allowing accurate trajectory simulation of the individual bodies in flight. The POST 2 multibody capability is intended to be general purpose and applicable to any parachute entry trajectory simulation. This research paper explains the motivation for multibody parachute simulation, discusses implementation methods, and presents validation of this capability.

  20. Automated boundary interaction force control of micromanipulators with in situ applications to microsurgery

    International Nuclear Information System (INIS)

    Eslami, Sohrab; Jalili, Nader

    2012-01-01

    Most recent works on miniature tasks are concentrated on developing tools to take advantage of the visual servoing feedback to control the ultra-small interaction forces. This paper spans an extensive platform for automatic controlling of boundary interaction forces with high precision in the level of micro/nano-Newton with extensive micro/nanoengineering applications such as the microsurgery. To this end, a comprehensive piezoresistive microcantilever (PMC) model considering the shear deformation and rotary inertia effects treating as the distributed-parameters model along with the Hertzian contact force is presented. The purpose of considering the Hertzian contact force model is to investigate the dynamic response of the interaction force between the microcantilever's tip and the specimen. Afterward, a control platform is introduced to automatically manipulate the PMC to follow an ideal micro/nano-interaction force. By using the integrated PMC with the micromanipulator and a digital signal processor, an intuitive programming code is written to incorporate the micromanipulator and the controller in a real-time framework. To calibrate and verify the induced voltage in the PMC, a self-sensing experiment on the piezoelectric microcantilever is carried out to warrant the calibration procedure. Some experiments are established to affirm the validity of the proposed control for the autonomous real-time tasks on the boundary interaction force control. Unlike the conventional research studies, the measured force here contributes as the feedback source in contrast to the vision feedback while force sensors possess more precision, productivity and small size. This technique has several potential applications listed but not limited to the micro/nanomanipulation, developing artificial biological systems (e.g., fabricating hydrogel for the scaffold), and medicine such as microsurgery. As a result, using the proposed platform, we are able to manipulate and control the

  1. Exploiting impedance shaping approaches to overcome force overshoots in delicate interaction tasks

    Directory of Open Access Journals (Sweden)

    Loris Roveda

    2016-09-01

    Full Text Available The aim of the presented article is to overcome the force overshoot issue in impedance based force tracking applications. Nowadays, light-weight manipulators are involved in high-accurate force control applications (such as polishing tasks, where the force overshoot issue is critical (i.e. damaging the component causing a production waste, exploiting the impedance control. Two main force tracking impedance control approaches are described in literature: (a set-point deformation and (b variable stiffness approaches. However, no contributions are directly related to the force overshoot issue. The presented article extends both such methodologies to analytically achieve the force overshoots avoidance in interaction tasks based on the on-line estimation of the interacting environment stiffness (available through an EKF. Both the proposed control algorithms allow to achieve a linear closed-loop dynamics for the coupled robot-environment system. Therefore, control gains can be analytically on-line calculated to achieve an over-damped closed-loop dynamics of the controlled coupled system. Control strategies have been validated in experiments, involving a KUKA LWR 4+. A probing task has been performed, representative of many industrial tasks (e.g. assembly tasks, in which a main force task direction is defined.

  2. Interaction force measurement between E. coli cells and nanoparticles immobilized surfaces by using AFM.

    Science.gov (United States)

    Zhang, Wen; Stack, Andrew G; Chen, Yongsheng

    2011-02-01

    To better understand environmental behaviors of nanoparticles (NPs), we used the atomic force microscopy (AFM) to measure interaction forces between E. coli cells and NPs immobilized on surfaces in an aqueous environment. The results showed that adhesion force strength was significantly influenced by particle size for both hematite (α-Fe(2)O(3)) and corundum (α-Al(2)O(3)) NPs whereas the effect on the repulsive force was not observed. The adhesion force decreased from 6.3±0.7nN to 0.8±0.4nN as hematite NPs increased from 26nm to 98nm in diameter. Corundum NPs exhibited a similar dependence of adhesion force on particle size. The Johnson-Kendall-Roberts (JKR) model was employed to estimate the contact area between E. coli cells and NPs, and based on the JKR model a new model that considers local effective contact area was developed. The prediction of the new model matched the size dependence of adhesion force in experimental results. Size effects on adhesion forces may originate from the difference in local effective contact areas as supported by our model. These findings provide fundamental information for interpreting the environmental behaviors and biological interactions of NPs, which barely have been addressed. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. 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.

  4. Probing the interactions between lignin and inorganic oxides using atomic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jingyu; Qian, Yong, E-mail: qianyong86@163.com; Deng, Yonghong; Liu, Di; Li, Hao; Qiu, Xueqing, E-mail: xueqingqiu66@163.com

    2016-12-30

    Graphical abstract: The interactions between lignin and inorganic oxides are quantitatively probed by atomic force microscopy, which is fundamental but beneficial for understanding and optimizing the absorption-dispersion and catalytic degradation processes of lignin. - Highlights: • The interactions between lignin and inorganic oxides are measured using AFM. • The adhesion forces between lignin and metal oxides are larger than that in nonmetal systems. • Hydrogen bond plays an important role in lignin-inorganic oxides system. - Abstract: Understanding the interactions between lignin and inorganic oxides has both fundamental and practical importance in industrial and energy fields. In this work, the specific interactions between alkali lignin (AL) and three inorganic oxide substrates in aqueous environment are quantitatively measured using atomic force microscopy (AFM). The results show that the average adhesion force between AL and metal oxide such as Al{sub 2}O{sub 3} or MgO is nearly two times bigger than that between AL and nonmetal oxide such as SiO{sub 2} due to the electrostatic difference and cation-π interaction. When 83% hydroxyl groups of AL is blocked by acetylation, the adhesion forces between AL and Al{sub 2}O{sub 3}, MgO and SiO{sub 2} decrease 43, 35 and 75% respectively, which indicate hydrogen bonds play an important role between AL and inorganic oxides, especially in AL-silica system.

  5. 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...

  6. Gauge unification of basic forces, particularly of gravitation with strong interactions

    International Nuclear Information System (INIS)

    Salam, A.

    1977-01-01

    An attempt is made to present a case for the use of both the Einstein--Weyl spin-two and the Yang--Mills spin-one gauge structures for describing strong interactions. By emphasizing both spin-one and -two aspects of this force, it is hoped that a unification of this force, on the one hand, with gravity theory and, on the other, with the electromagnetic and weak interactions can be achieved. A Puppi type of tetrahedral interralation of fundamental forces, with the strong force playing a pivotal role due to its mediation through both spin-one and -two quanta, is proposed. It is claimed that the gauge invariance of gravity theory permits the use of ambuguity-free nonpolynomial techniques and thereby the securing of relistic regularization in gravity-modified field theories with the Newtonian constant G/sub N/ providing a relistic cutoff. 37 references

  7. Nucleon-deuteron breakup quantities calculated with separable interactions including tensor forces and P-wave interactions

    International Nuclear Information System (INIS)

    Bruinsma, J.; Wageningen, R. van

    1977-01-01

    Nucleon-deuteron breakup calculations at a nucleon bombarding energy of 22.7 MeV have been performed with separable interactions including a tensor force and P-wave interactions. Differential cross sections and a selection of polarization quantities have been computed for special regions of the phase space. The influence of a tensor force and P-wave interactions on the differential cross section is of the order of 20%. Large discrepancies between theory and experiment occur for the vector analyzing powers, both for the kinematically complete and for the incomplete situation. The calculations show that there are kinematical situations in which the differential cross sections and the tensor analyzing powers are sufficiently large to make measurements feasible. (Auth.)

  8. Interaction force and motion estimators facilitating impedance control of the upper limb rehabilitation robot.

    Science.gov (United States)

    Mancisidor, Aitziber; Zubizarreta, Asier; Cabanes, Itziar; Bengoa, Pablo; Jung, Je Hyung

    2017-07-01

    In order to enhance the performance of rehabilitation robots, it is imperative to know both force and motion caused by the interaction between user and robot. However, common direct measurement of both signals through force and motion sensors not only increases the complexity of the system but also impedes affordability of the system. As an alternative of the direct measurement, in this work, we present new force and motion estimators for the proper control of the upper-limb rehabilitation Universal Haptic Pantograph (UHP) robot. The estimators are based on the kinematic and dynamic model of the UHP and the use of signals measured by means of common low-cost sensors. In order to demonstrate the effectiveness of the estimators, several experimental tests were carried out. The force and impedance control of the UHP was implemented first by directly measuring the interaction force using accurate extra sensors and the robot performance was compared to the case where the proposed estimators replace the direct measured values. The experimental results reveal that the controller based on the estimators has similar performance to that using direct measurement (less than 1 N difference in root mean square error between two cases), indicating that the proposed force and motion estimators can facilitate implementation of interactive controller for the UHP in robotmediated rehabilitation trainings.

  9. Higher order terms of the nonlinear forces in plasmas with collisions at laser interaction

    International Nuclear Information System (INIS)

    Kentwell, G.W.; Hora, H.

    1980-01-01

    The evaluation of the general expression of the nonlinear force of laser-plasma interaction showed discrepancies depending on the assumptions of the phase and collisions in the expressions used for E and H. While the first order terms of the derivations are remaining unchanged, new third order terms are found for the case of perpendicular incidence without collisions. With collisions, the additional non-pondermotive terms are derived to be more general than known before. It is then possible to evaluate the forces for oblique incidence with collisions and find an absorption caused force in the plane of the plasma surface. (author)

  10. Mechanism of transient force augmentation varying with two distinct timescales for interacting vortex rings

    Science.gov (United States)

    Fu, Zhidong; Qin, Suyang; Liu, Hong

    2014-01-01

    The dynamics of dual vortex ring flows is studied experimentally and numerically in a model system that consists of a piston-cylinder apparatus. The flows are generated by double identical strokes which have the velocity profile characterized by the sinusoidal function of half the period. By calculating the total wake impulse in two strokes in the experiments, it is found that the average propulsive force increases by 50% in the second stroke for the sufficiently small stroke length, compared with the first stroke. In the numerical simulations, two types of transient force augmentation are revealed, there being the transient force augmentation for the small stroke lengths and the absolute transient force augmentation for the large stroke lengths. The relative transient force augmentation increases to 78% for L/D = 1, while the absolute transient force augmentation for L/D = 4 is twice as much as that for L/D = 1. Further investigation demonstrates that the force augmentation is attributed to the interaction between vortex rings, which induces transport of vortex impulse and more evident fluid entrainment. The critical situation of vortex ring separation is defined and indicated, with vortex spacing falling in a narrow gap when the stroke lengths vary. A new model is proposed concerning the limiting process of impulse, further suggesting that apart from vortex formation timescale, vortex spacing should be interpreted as an independent timescale to reflect the dynamics of vortex interaction.

  11. 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

  12. 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.

  13. Strength of tensor force and s-d-shell effective interactions

    International Nuclear Information System (INIS)

    Jiang, M.; Machleidt, R.; Stout, D.B.; Kuo, T.T.S.

    1989-01-01

    The s-d-shell effective interaction is derived from the Bonn NN potential, using a G-matrix folded-diagram method. It is found that due to the relatively weak-tensor-force characteristic for the Bonn potential, the effective interaction matrix elements, particularly those with isospin T=0, come out generally more attractive than in previous derivations which were based on conventional local strong-tensor-force NN potentials. This renders the results obtained with the Bonn potential in considerably better agreement with the recent s-d-shell matrix elements of Wildenthal

  14. Seismic response of pile foundations and pile forces caused by kinematic and inertial interaction

    International Nuclear Information System (INIS)

    Hartmann, H.G.; Waas, G.

    1985-01-01

    The horizontal motion and pile forces of pile groups subjected to earthquake excitation are analysed. The piles are modelled as linear elastic beam elements embedded in a layered linear visco-elastic soil medium. Pile-soil-pile interaction is included. The earthquake excitation results from vertically propagating shear waves. Kinematic and inertial interaction effects on foundation motion and pile forces are studied for a single pile, a small pile group and a large pile group. Soft and stiff soil conditions are considered, and the effect of a flexible vs. a rigid halfspace below the soil layers is shown. (orig.)

  15. Quantitative analysis of tip-sample interaction in non-contact scanning force spectroscopy

    International Nuclear Information System (INIS)

    Palacios-Lidon, Elisa; Colchero, Jaime

    2006-01-01

    Quantitative characterization of tip-sample interaction in scanning force microscopy is fundamental for optimum image acquisition as well as data interpretation. In this work we discuss how to characterize the electrostatic and van der Waals contribution to tip-sample interaction in non-contact scanning force microscopy precisely. The spectroscopic technique presented is based on the simultaneous measurement of cantilever deflection, oscillation amplitude and frequency shift as a function of tip-sample voltage and tip-sample distance as well as on advanced data processing. Data are acquired at a fixed lateral position as interaction images, with the bias voltage as fast scan, and tip-sample distance as slow scan. Due to the quadratic dependence of the electrostatic interaction with tip-sample voltage the van der Waals force can be separated from the electrostatic force. Using appropriate data processing, the van der Waals interaction, the capacitance and the contact potential can be determined as a function of tip-sample distance. The measurement of resonance frequency shift yields very high signal to noise ratio and the absolute calibration of the measured quantities, while the acquisition of cantilever deflection allows the determination of the tip-sample distance

  16. Interactions between Rotavirus and Suwannee River Organic Matter: Aggregation, Deposition, and Adhesion Force Measurement

    KAUST Repository

    Gutierrez, Leonardo

    2012-08-21

    Interactions between rotavirus and Suwannee River natural organic matter (NOM) were studied by time-resolved dynamic light scattering, quartz crystal microbalance, and atomic force microscopy. In NOM-containing NaCl solutions of up to 600 mM, rotavirus suspension remained stable for over 4 h. Atomic force microscopy (AFM) measurement for interaction force decay length at different ionic strengths showed that nonelectrostatic repulsive forces were mainly responsible for eliminating aggregation in NaCl solutions. Aggregation rates of rotavirus in solutions containing 20 mg C/L increased with divalent cation concentration until reaching a critical coagulation concentration of 30 mM CaCl2 or 70 mM MgCl2. Deposition kinetics of rotavirus on NOM-coated silica surface was studied using quartz crystal microbalance. Experimental attachment efficiencies for rotavirus adsorption to NOM-coated surface in MgCl2 solution were lower than in CaCl2 solution at a given divalent cation concentration. Stronger adhesion force was measured for virus-virus and virus-NOM interactions in CaCl2 solution compared to those in MgCl2 or NaCl solutions at the same ionic strength. This study suggested that divalent cation complexation with carboxylate groups in NOM and on virus surface was an important mechanism in the deposition and aggregation kinetics of rotavirus. © 2012 American Chemical Society.

  17. Lepton Flavorful Fifth Force and Depth-Dependent Neutrino Matter Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Wise, Mark B. [Caltech; Zhang, Yue [Northwestern U.

    2018-03-01

    We consider a fifth force to be an interaction that couples to matter with a strength that grows with the number of atoms. In addition to competing with the strength of gravity a fifth force can give rise to violations of the equivalence principle. Current long range constraints on the strength and range of fifth forces are very impressive. Amongst possible fifth forces are those that couple to lepton flavorful charges $L_e-L_{\\mu}$ or $L_e-L_{\\tau}$. They have the property that their range and strength are also constrained by neutrino interactions with matter. In this brief note we review the existing constraints on the allowed parameter space in gauged $U(1)_{L_e-L_{\\mu}, L_{\\tau}}$. We find two regions where neutrino oscillation experiments are at the frontier of probing such a new force. In particular, there is an allowed range of parameter space where neutrino matter interactions relevant for long baseline oscillation experiments depend on the depth of the neutrino beam below the surface of the earth.

  18. 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.

  19. Interactions between internal forces, body stiffness, and fluid environment in a neuromechanical model of lamprey swimming.

    Science.gov (United States)

    Tytell, Eric D; Hsu, Chia-Yu; Williams, Thelma L; Cohen, Avis H; Fauci, Lisa J

    2010-11-16

    Animal movements result from a complex balance of many different forces. Muscles produce force to move the body; the body has inertial, elastic, and damping properties that may aid or oppose the muscle force; and the environment produces reaction forces back on the body. The actual motion is an emergent property of these interactions. To examine the roles of body stiffness, muscle activation, and fluid environment for swimming animals, a computational model of a lamprey was developed. The model uses an immersed boundary framework that fully couples the Navier-Stokes equations of fluid dynamics with an actuated, elastic body model. This is the first model at a Reynolds number appropriate for a swimming fish that captures the complete fluid-structure interaction, in which the body deforms according to both internal muscular forces and external fluid forces. Results indicate that identical muscle activation patterns can produce different kinematics depending on body stiffness, and the optimal value of stiffness for maximum acceleration is different from that for maximum steady swimming speed. Additionally, negative muscle work, observed in many fishes, emerges at higher tail beat frequencies without sensory input and may contribute to energy efficiency. Swimming fishes that can tune their body stiffness by appropriately timed muscle contractions may therefore be able to optimize the passive dynamics of their bodies to maximize peak acceleration or swimming speed.

  20. Measurement of Vehicle-Bridge-Interaction force using dynamic tire pressure monitoring

    Science.gov (United States)

    Chen, Zhao; Xie, Zhipeng; Zhang, Jian

    2018-05-01

    The Vehicle-Bridge-Interaction (VBI) force, i.e., the normal contact force of a tire, is a key component in the VBI mechanism. The VBI force measurement can facilitate experimental studies of the VBI as well as input-output bridge structural identification. This paper introduces an innovative method for calculating the interaction force by using dynamic tire pressure monitoring. The core idea of the proposed method combines the ideal gas law and a basic force model to build a relationship between the tire pressure and the VBI force. Then, unknown model parameters are identified by the Extended Kalman Filter using calibration data. A signal filter based on the wavelet analysis is applied to preprocess the effect that the tire rotation has on the pressure data. Two laboratory tests were conducted to check the proposed method's validity. The effects of different road irregularities, loads and forward velocities were studied. Under the current experiment setting, the proposed method was robust to different road irregularities, and the increase in load and velocity benefited the performance of the proposed method. A high-speed test further supported the use of this method in rapid bridge tests. Limitations of the derived theories and experiment were also discussed.

  1. Direct measurements of intermolecular forces by chemical force microscopy

    Science.gov (United States)

    Vezenov, Dmitri Vitalievich

    1999-12-01

    changes in ionization state on SAM surfaces. The phase contrast in tapping mode AFM between chemically distinct monolayer regions and corresponding adhesion forces were found to be directly correlated. Thus, both friction and intermittent contact CFM images could be interpreted in terms of the strength of intermolecular interactions. CFM was also used to probe biomolecular interactions. Separation forces between complementary oligonucleotide strands were significantly larger than the forces measured between noncomplementary strands and were consistent with the unbinding of a single DNA duplex. CFM data provided a direct measure of the forces required to elastically deform, structurally-transform and separate well-defined, synthetic duplexes into single strand oligonucleotides.

  2. Interaction potential and repulsive force between atoms whose internuclear separations are small

    International Nuclear Information System (INIS)

    Barbaro, Jacques

    1971-01-01

    The Thomas-Fermi equation is solved for the homonuclear diatomic molecule. The electronic density and electrostatic potential at each point are used to calculate energies and interaction potentials for very small internuclear separation distances. The repulsive force between atoms is derived by means of the virial theorem. (author) [fr

  3. Resistance to moment-normal force interaction of I-shaped steel sections

    NARCIS (Netherlands)

    Rombouts, I.M.J.; Snijder, H.H.; Dekker, R.W.A.; Teeuwen, P.A.

    2016-01-01

    This paper describes the assessment of the EN 1993-1-1 design rules for cross-section resistance to moment-normal force interaction (M-Ninteraction). Besides the fact that the Eurocode design rules showunconservative predictions of the reduced plastic moment capacity for the presence of relatively

  4. A force-based, parallel assay for the quantification of protein-DNA interactions.

    Science.gov (United States)

    Limmer, Katja; Pippig, Diana A; Aschenbrenner, Daniela; Gaub, Hermann E

    2014-01-01

    Analysis of transcription factor binding to DNA sequences is of utmost importance to understand the intricate regulatory mechanisms that underlie gene expression. Several techniques exist that quantify DNA-protein affinity, but they are either very time-consuming or suffer from possible misinterpretation due to complicated algorithms or approximations like many high-throughput techniques. We present a more direct method to quantify DNA-protein interaction in a force-based assay. In contrast to single-molecule force spectroscopy, our technique, the Molecular Force Assay (MFA), parallelizes force measurements so that it can test one or multiple proteins against several DNA sequences in a single experiment. The interaction strength is quantified by comparison to the well-defined rupture stability of different DNA duplexes. As a proof-of-principle, we measured the interaction of the zinc finger construct Zif268/NRE against six different DNA constructs. We could show the specificity of our approach and quantify the strength of the protein-DNA interaction.

  5. A force-based, parallel assay for the quantification of protein-DNA interactions.

    Directory of Open Access Journals (Sweden)

    Katja Limmer

    Full Text Available Analysis of transcription factor binding to DNA sequences is of utmost importance to understand the intricate regulatory mechanisms that underlie gene expression. Several techniques exist that quantify DNA-protein affinity, but they are either very time-consuming or suffer from possible misinterpretation due to complicated algorithms or approximations like many high-throughput techniques. We present a more direct method to quantify DNA-protein interaction in a force-based assay. In contrast to single-molecule force spectroscopy, our technique, the Molecular Force Assay (MFA, parallelizes force measurements so that it can test one or multiple proteins against several DNA sequences in a single experiment. The interaction strength is quantified by comparison to the well-defined rupture stability of different DNA duplexes. As a proof-of-principle, we measured the interaction of the zinc finger construct Zif268/NRE against six different DNA constructs. We could show the specificity of our approach and quantify the strength of the protein-DNA interaction.

  6. Interaction forces between salivary proteins and Streptococcus mutans with and without antigen I/II

    NARCIS (Netherlands)

    Xu, C.P.; Belt-Gritter, van de B.; Dijkstra, R.J.B.; Norde, W.; Mei, van der H.C.; Busscher, H.J.

    2007-01-01

    The antigen I/II family of surface proteins is expressed by oral streptococci, including Streptococcus mutans, and mediates specific binding to, among others, salivary films. The aim of this study was to investigate the interaction forces between salivary proteins and S. mutans with (LT11) and

  7. Influence of atomic force microscope tip-sample interaction on the study of scaling behavior

    NARCIS (Netherlands)

    Aue, J.; de Hosson, J.T.M.

    1997-01-01

    Images acquired with atomic force microscopy are based on tip-sample interaction. It is shown that using scanning probe techniques for determining scaling parameters of a surface leads to an underestimate of the actual scaling dimension, due to the dilation of tip and surface. How much we

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

    Science.gov (United States)

    Hu, Xiaotang; Li, Hongbin

    2014-10-01

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

  9. Investigation of a mutual interaction force at different pressure amplitudes in sulfuric acid

    International Nuclear Information System (INIS)

    Rezaee, Nastaran; Sadighi-Bonabi, Rasoul; Mirheydari, Mona; Ebrahimi, Homa

    2011-01-01

    This paper investigates the secondary Bjerknes force for two oscillating bubbles in various pressure amplitudes in a concentration of 95% sulfuric acid. The equilibrium radii of the bubbles are assumed to be smaller than 10 μm at a frequency of 37 kHz in various strong driving acoustical fields around 2.0 bars (1 bar=10 5 Pa). The secondary Bjerknes force is investigated in uncoupled and coupled states between the bubbles, with regard to the quasi-adiabatic model for the bubble interior. It finds that the value of the secondary Bjerknes force depends on the driven pressure of sulfuric acid and its amount would be increased by liquid pressure amplitude enhancement. The results show that the repulsion area of the interaction force would be increased by increasing the driven pressure because of nonlinear oscillation of bubbles. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  10. A self-interacting partially directed walk subject to a force

    Energy Technology Data Exchange (ETDEWEB)

    Brak, R; Owczarek, A L [Department of Mathematics and Statistics, University of Melbourne, Parkville, Victoria 3010 (Australia); Dyke, P; Lee, J; Whittington, S G [Department of Chemistry, University of Toronto, Toronto M5S 3H6 (Canada); Prellberg, T [School of Mathematical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom); Rechnitzer, A [Department of Mathematics, University of British Columbia, Vancouver V6K 1ZT (Canada)

    2009-02-27

    We consider a directed walk model of a homopolymer (in two dimensions) which is self-interacting and can undergo a collapse transition, subject to an applied tensile force. We review and interpret all the results already in the literature concerning the case where this force is in the preferred direction of the walk. We consider the force extension curves at different temperatures as well as the critical-force temperature curve. We demonstrate that this model can be analysed rigorously for all key quantities of interest even when there may not be explicit expressions for these quantities available. We show which of the techniques available can be extended to the full model, where the force has components in the preferred direction and the direction perpendicular to this. Whilst the solution of the generating function is available, its analysis is far more complicated and not all the rigorous techniques are available. However, many results can be extracted including the location of the critical point which gives the general critical-force temperature curve. Lastly, we generalize the model to a three-dimensional analogue and show that several key properties can be analysed if the force is restricted to the plane of preferred directions.

  11. Reconsideration of dynamic force spectroscopy analysis of streptavidin-biotin interactions.

    Science.gov (United States)

    Taninaka, Atsushi; Takeuchi, Osamu; Shigekawa, Hidemi

    2010-05-13

    To understand and design molecular functions on the basis of molecular recognition processes, the microscopic probing of the energy landscapes of individual interactions in a molecular complex and their dependence on the surrounding conditions is of great importance. Dynamic force spectroscopy (DFS) is a technique that enables us to study the interaction between molecules at the single-molecule level. However, the obtained results differ among previous studies, which is considered to be caused by the differences in the measurement conditions. We have developed an atomic force microscopy technique that enables the precise analysis of molecular interactions on the basis of DFS. After verifying the performance of this technique, we carried out measurements to determine the landscapes of streptavidin-biotin interactions. The obtained results showed good agreement with theoretical predictions. Lifetimes were also well analyzed. Using a combination of cross-linkers and the atomic force microscope that we developed, site-selective measurement was carried out, and the steps involved in bonding due to microscopic interactions are discussed using the results obtained by site-selective analysis.

  12. Nonlinear Dynamics of Cantilever-Sample Interactions in Atomic Force Microscopy

    Science.gov (United States)

    Cantrell, John H.; Cantrell, Sean A.

    2010-01-01

    The interaction of the cantilever tip of an atomic force microscope (AFM) with the sample surface is obtained by treating the cantilever and sample as independent systems coupled by a nonlinear force acting between the cantilever tip and a volume element of the sample surface. The volume element is subjected to a restoring force from the remainder of the sample that provides dynamical equilibrium for the combined systems. The model accounts for the positions on the cantilever of the cantilever tip, laser probe, and excitation force (if any) via a basis set of set of orthogonal functions that may be generalized to account for arbitrary cantilever shapes. The basis set is extended to include nonlinear cantilever modes. The model leads to a pair of coupled nonlinear differential equations that are solved analytically using a matrix iteration procedure. The effects of oscillatory excitation forces applied either to the cantilever or to the sample surface (or to both) are obtained from the solution set and applied to the to the assessment of phase and amplitude signals generated by various acoustic-atomic force microscope (A-AFM) modalities. The influence of bistable cantilever modes of on AFM signal generation is discussed. The effects on the cantilever-sample surface dynamics of subsurface features embedded in the sample that are perturbed by surface-generated oscillatory excitation forces and carried to the cantilever via wave propagation are accounted by the Bolef-Miller propagating wave model. Expressions pertaining to signal generation and image contrast in A-AFM are obtained and applied to amplitude modulation (intermittent contact) atomic force microscopy and resonant difference-frequency atomic force ultrasonic microscopy (RDF-AFUM). The influence of phase accumulation in A-AFM on image contrast is discussed, as is the effect of hard contact and maximum nonlinearity regimes of A-AFM operation.

  13. Surface force analysis of molecular interfacial interactions of proteins and lipids with polymeric biomaterials

    International Nuclear Information System (INIS)

    Hamilton-Brown, P.; Griesser, H.J.; Meagher, L.

    2001-01-01

    Full text: Adverse biological responses to biomedical devices are often caused by the irreversible accumulation of biological deposits onto the surfaces of devices. Such deposits cause blocking of artificial blood vessels, fibrous encapsulation of soft tissue regenerative devices, 'fouling' of contact lenses, secondary cataracts on intraocular lenses, and other undesirable events that interfere with the intended functions of biomedical devices. The formation of deposits is triggered by an initial stage in which various proteins and lipids rapidly adsorb onto the synthetic material surface; further biological molecules and ultimately cellular entities (e.g., host cells, bacteria) then settle onto the initial adsorbed layer. Hence, to avoid or control the accumulation of biological deposits, molecular understanding is required of the initial adsorption processes. Such adsorption is caused by attractive interfacial forces, which we are characterising by the use of a novel method. In the present study, polymeric thin film coatings, polyethylene oxide (PEO), and polysaccharide coatings have been analysed in terms of their surface forces and the ensuing propensity for protein and lipid adsorption. Interfacial forces are measured using atomic force microscopy (AFM) with a colloid-modified tip in a liquid cell using solutions of physiological pH and ionic strength. The chemical composition and uniformity of the coatings was characterised by X-ray Photon Spectroscopy (XPS). For a polymeric solid coating, repulsive forces have been measured against a silica colloid probe, and the dominant surface force is electrostatic. For the highly hydrated, 'soft' PEO and polysaccharide coatings, on the other hand, steric/entropic forces are also significant and contribute to interfacial interactions with proteins and lipids. In one system we have observed a time dependence of the electrostatic surface potential, which affects interaction with charged proteins. Force measurements were

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

    Science.gov (United States)

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

    2013-03-01

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

  15. Parabolized Stability Equations analysis of nonlinear interactions with forced eigenmodes to control subsonic jet instabilities

    International Nuclear Information System (INIS)

    Itasse, Maxime; Brazier, Jean-Philippe; Léon, Olivier; Casalis, Grégoire

    2015-01-01

    Nonlinear evolution of disturbances in an axisymmetric, high subsonic, high Reynolds number hot jet with forced eigenmodes is studied using the Parabolized Stability Equations (PSE) approach to understand how modes interact with one another. Both frequency and azimuthal harmonic interactions are analyzed by setting up one or two modes at higher initial amplitudes and various phases. While single mode excitation leads to harmonic growth and jet noise amplification, controlling the evolution of a specific mode has been made possible by forcing two modes (m 1 , n 1 ), (m 2 , n 2 ), such that the difference in azimuth and in frequency matches the desired “target” mode (m 1 − m 2 , n 1 − n 2 ). A careful setup of the initial amplitudes and phases of the forced modes, defined as the “killer” modes, has allowed the minimizing of the initially dominant instability in the near pressure field, as well as its estimated radiated noise with a 15 dB loss. Although an increase of the overall sound pressure has been found in the range of azimuth and frequency analyzed, the present paper reveals the possibility to make the initially dominant instability ineffective acoustically using nonlinear interactions with forced eigenmodes

  16. Nanophotonic force microscopy: characterizing particle-surface interactions using near-field photonics.

    Science.gov (United States)

    Schein, Perry; Kang, Pilgyu; O'Dell, Dakota; Erickson, David

    2015-02-11

    Direct measurements of particle-surface interactions are important for characterizing the stability and behavior of colloidal and nanoparticle suspensions. Current techniques are limited in their ability to measure pico-Newton scale interaction forces on submicrometer particles due to signal detection limits and thermal noise. Here we present a new technique for making measurements in this regime, which we refer to as nanophotonic force microscopy. Using a photonic crystal resonator, we generate a strongly localized region of exponentially decaying, near-field light that allows us to confine small particles close to a surface. From the statistical distribution of the light intensity scattered by the particle we are able to map out the potential well of the trap and directly quantify the repulsive force between the nanoparticle and the surface. As shown in this Letter, our technique is not limited by thermal noise, and therefore, we are able to resolve interaction forces smaller than 1 pN on dielectric particles as small as 100 nm in diameter.

  17. Parabolized Stability Equations analysis of nonlinear interactions with forced eigenmodes to control subsonic jet instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Itasse, Maxime, E-mail: Maxime.Itasse@onera.fr; Brazier, Jean-Philippe, E-mail: Jean-Philippe.Brazier@onera.fr; Léon, Olivier, E-mail: Olivier.Leon@onera.fr; Casalis, Grégoire, E-mail: Gregoire.Casalis@onera.fr [Onera - The French Aerospace Lab, F-31055 Toulouse (France)

    2015-08-15

    Nonlinear evolution of disturbances in an axisymmetric, high subsonic, high Reynolds number hot jet with forced eigenmodes is studied using the Parabolized Stability Equations (PSE) approach to understand how modes interact with one another. Both frequency and azimuthal harmonic interactions are analyzed by setting up one or two modes at higher initial amplitudes and various phases. While single mode excitation leads to harmonic growth and jet noise amplification, controlling the evolution of a specific mode has been made possible by forcing two modes (m{sub 1}, n{sub 1}), (m{sub 2}, n{sub 2}), such that the difference in azimuth and in frequency matches the desired “target” mode (m{sub 1} − m{sub 2}, n{sub 1} − n{sub 2}). A careful setup of the initial amplitudes and phases of the forced modes, defined as the “killer” modes, has allowed the minimizing of the initially dominant instability in the near pressure field, as well as its estimated radiated noise with a 15 dB loss. Although an increase of the overall sound pressure has been found in the range of azimuth and frequency analyzed, the present paper reveals the possibility to make the initially dominant instability ineffective acoustically using nonlinear interactions with forced eigenmodes.

  18. Converting Biomolecular Modelling Data Based on an XML Representation

    Directory of Open Access Journals (Sweden)

    Sun Yudong

    2008-06-01

    Full Text Available Biomolecular modelling has provided computational simulation based methods for investigating biological processes from quantum chemical to cellular levels. Modelling such microscopic processes requires atomic description of a biological system and conducts in fine timesteps. Consequently the simulations are extremely computationally demanding. To tackle this limitation, different biomolecular models have to be integrated in order to achieve high-performance simulations. The integration of diverse biomolecular models needs to convert molecular data between different data representations of different models. This data conversion is often non-trivial, requires extensive human input and is inevitably error prone. In this paper we present an automated data conversion method for biomolecular simulations between molecular dynamics and quantum mechanics/molecular mechanics models. Our approach is developed around an XML data representation called BioSimML (Biomolecular Simulation Markup Language. BioSimML provides a domain specific data representation for biomolecular modelling which can effciently support data interoperability between different biomolecular simulation models and data formats.

  19. 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.

  20. 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

  1. Molecular Theory and the Effects of Solute Attractive Forces on Hydrophobic Interactions.

    Science.gov (United States)

    Chaudhari, Mangesh I; Rempe, Susan B; Asthagiri, D; Tan, L; Pratt, L R

    2016-03-03

    The role of solute attractive forces on hydrophobic interactions is studied by coordinated development of theory and simulation results for Ar atoms in water. We present a concise derivation of the local molecular field (LMF) theory for the effects of solute attractive forces on hydrophobic interactions, a derivation that clarifies the close relation of LMF theory to the EXP approximation applied to this problem long ago. The simulation results show that change from purely repulsive atomic solute interactions to include realistic attractive interactions diminishes the strength of hydrophobic bonds. For the Ar-Ar rdfs considered pointwise, the numerical results for the effects of solute attractive forces on hydrophobic interactions are opposite in sign and larger in magnitude than predicted by LMF theory. That comparison is discussed from the point of view of quasichemical theory, and it is suggested that the first reason for this difference is the incomplete evaluation within LMF theory of the hydration energy of the Ar pair. With a recent suggestion for the system-size extrapolation of the required correlation function integrals, the Ar-Ar rdfs permit evaluation of osmotic second virial coefficients B2. Those B2's also show that incorporation of attractive interactions leads to more positive (repulsive) values. With attractive interactions in play, B2 can change from positive to negative values with increasing temperatures. This is consistent with the puzzling suggestions of decades ago that B2 ≈ 0 for intermediate cases of temperature or solute size. In all cases here, B2 becomes more attractive with increasing temperature.

  2. Density-dependent effective baryon–baryon interaction from chiral three-baryon forces

    Energy Technology Data Exchange (ETDEWEB)

    Petschauer, Stefan, E-mail: stefan.petschauer@ph.tum.de [Physik Department, Technische Universität München, D-85747 Garching (Germany); Haidenbauer, Johann [Institute for Advanced Simulation, Institut für Kernphysik and Jülich Center for Hadron Physics, Forschungszentrum Jülich, D-52425 Jülich (Germany); Kaiser, Norbert [Physik Department, Technische Universität München, D-85747 Garching (Germany); Meißner, Ulf-G. [Institute for Advanced Simulation, Institut für Kernphysik and Jülich Center for Hadron Physics, Forschungszentrum Jülich, D-52425 Jülich (Germany); Helmholtz-Institut für Strahlen- und Kernphysik, Universität Bonn, D-53115 Bonn (Germany); Bethe Center for Theoretical Physics, Universität Bonn, D-53115 Bonn (Germany); Weise, Wolfram [Physik Department, Technische Universität München, D-85747 Garching (Germany)

    2017-01-15

    A density-dependent effective potential for the baryon–baryon interaction in the presence of the (hyper)nuclear medium is constructed, based on the leading (irreducible) three-baryon forces derived within SU(3) chiral effective field theory. We evaluate the contributions from three classes: contact terms, one-pion exchange and two-pion exchange. In the strangeness-zero sector we recover the known result for the in-medium nucleon–nucleon interaction. Explicit expressions for the ΛN in-medium potential in (asymmetric) nuclear matter are presented. Our results are suitable for implementation into calculations of (hyper)nuclear matter. In order to estimate the low-energy constants of the leading three-baryon forces we introduce the decuplet baryons as explicit degrees of freedom and construct the relevant terms in the minimal non-relativistic Lagrangian. With these, the constants are estimated through decuplet saturation. Utilizing this approximation we provide numerical results for the effect of the three-body force in symmetric nuclear matter and pure neutron matter on the ΛN interaction. A moderate repulsion that increases with density is found in comparison to the free ΛN interaction.

  3. Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix.

    Science.gov (United States)

    Kubow, Kristopher E; Vukmirovic, Radmila; Zhe, Lin; Klotzsch, Enrico; Smith, Michael L; Gourdon, Delphine; Luna, Sheila; Vogel, Viola

    2015-08-14

    Despite the crucial role of extracellular matrix (ECM) in directing cell fate in healthy and diseased tissues--particularly in development, wound healing, tissue regeneration and cancer--the mechanisms that direct the assembly and regulate hierarchical architectures of ECM are poorly understood. Collagen I matrix assembly in vivo requires active fibronectin (Fn) fibrillogenesis by cells. Here we exploit Fn-FRET probes as mechanical strain sensors and demonstrate that collagen I fibres preferentially co-localize with more-relaxed Fn fibrils in the ECM of fibroblasts in cell culture. Fibre stretch-assay studies reveal that collagen I's Fn-binding domain is responsible for the mechano-regulated interaction. Furthermore, we show that Fn-collagen interactions are reciprocal: relaxed Fn fibrils act as multivalent templates for collagen assembly, but once assembled, collagen fibres shield Fn fibres from being stretched by cellular traction forces. Thus, in addition to the well-recognized, force-regulated, cell-matrix interactions, forces also tune the interactions between different structural ECM components.

  4. Multi-Axis Force Sensor for Human-Robot Interaction Sensing in a Rehabilitation Robotic Device.

    Science.gov (United States)

    Grosu, Victor; Grosu, Svetlana; Vanderborght, Bram; Lefeber, Dirk; Rodriguez-Guerrero, Carlos

    2017-06-05

    Human-robot interaction sensing is a compulsory feature in modern robotic systems where direct contact or close collaboration is desired. Rehabilitation and assistive robotics are fields where interaction forces are required for both safety and increased control performance of the device with a more comfortable experience for the user. In order to provide an efficient interaction feedback between the user and rehabilitation device, high performance sensing units are demanded. This work introduces a novel design of a multi-axis force sensor dedicated for measuring pelvis interaction forces in a rehabilitation exoskeleton device. The sensor is conceived such that it has different sensitivity characteristics for the three axes of interest having also movable parts in order to allow free rotations and limit crosstalk errors. Integrated sensor electronics make it easy to acquire and process data for a real-time distributed system architecture. Two of the developed sensors are integrated and tested in a complex gait rehabilitation device for safe and compliant control.

  5. Interaction between local parameters of two-phase flow and random forces on a cylinder

    International Nuclear Information System (INIS)

    Sylviane Pascal-Ribot; Yves Blanchet; Franck Baj; Phillippe Piteau

    2005-01-01

    Full text of publication follows: In the frame of assessments of steam generator tube bundle vibrations, a study was conducted in order to investigate the effects of an air/water flow on turbulent buffeting forces induced on a cylinder. The main purpose is to relate the physical parameters characterizing an air/water two-phase crossflow with the structural loading of a fixed cylindrical tube. In this first approach, the experiments are carried out in a rectangular acrylic test section supplied with a vertical upward bubbly flow. This flow is transversally impeded by a fixed rigid 12,15 mm diameter cylinder. Different turbulence grids are used in order to modify two-phase characteristics such as bubble diameter, void fraction profile, fluctuation parameters. Preliminarily, a dimensional analysis of fluid-structure interaction under two-phase turbulent solicitations has enabled to identify a list of physically relevant variables which must be measured to evaluate the random forces. The meaning of these relevant parameters as well as the effect of flow patterns are discussed. Direct measurements of two-phase flow parameters are performed simultaneously with measurements of forces exerted on the cylinder. The main descriptive parameters of a two-phase flow are measured using a bi-optical probe, in particular void fraction profiles, interfacial velocities, bubble diameters, void fraction fluctuations. In the same time, the magnitude of random forces caused by two-phase flow is measured with a force transducer. A thorough analysis of the experimental data is then undertaken in order to correlate physical two-phase mechanisms with the random forces exerted on the cylinder. The hypotheses made while applying the dimensional analysis are verified and their pertinence is discussed. Finally, physical parameters involved in random buffeting forces applied on a transverse tube are proposed to scale the spectral magnitude of these forces and comparisons with other authors

  6. Polyphilic Interactions as Structural Driving Force Investigated by Molecular Dynamics Simulation (Project 7

    Directory of Open Access Journals (Sweden)

    Christopher Peschel

    2017-09-01

    Full Text Available We investigated the effect of fluorinated molecules on dipalmitoylphosphatidylcholine (DPPC bilayers by force-field molecular dynamics simulations. In the first step, we developed all-atom force-field parameters for additive molecules in membranes to enable an accurate description of those systems. On the basis of this force field, we performed extensive simulations of various bilayer systems containing different additives. The additive molecules were chosen to be of different size and shape, and they included small molecules such as perfluorinated alcohols, but also more complex molecules. From these simulations, we investigated the structural and dynamic effects of the additives on the membrane properties, as well as the behavior of the additive molecules themselves. Our results are in good agreement with other theoretical and experimental studies, and they contribute to a microscopic understanding of interactions, which might be used to specifically tune membrane properties by additives in the future.

  7. Differential MS2 Interaction with Food Contact Surfaces Determined by Atomic Force Microscopy and Virus Recovery.

    Science.gov (United States)

    Shim, J; Stewart, D S; Nikolov, A D; Wasan, D T; Wang, R; Yan, R; Shieh, Y C

    2017-12-15

    Enteric viruses are recognized as major etiologies of U.S. foodborne infections. These viruses are easily transmitted via food contact surfaces. Understanding virus interactions with surfaces may facilitate the development of improved means for their removal, thus reducing transmission. Using MS2 coliphage as a virus surrogate, the strength of virus adhesion to common food processing and preparation surfaces of polyvinyl chloride (PVC) and glass was assessed by atomic force microscopy (AFM) and virus recovery assays. The interaction forces of MS2 with various surfaces were measured from adhesion peaks in force-distance curves registered using a spherical bead probe preconjugated with MS2 particles. MS2 in phosphate-buffered saline (PBS) demonstrated approximately 5 times less adhesion force to glass (0.54 nN) than to PVC (2.87 nN) ( P force for PVC (∼0 nN) and consistently increased virus recovery by 19%. With direct and indirect evidence of virus adhesion, this study illustrated a two-way assessment of virus adhesion for the initial evaluation of potential means to mitigate virus adhesion to food contact surfaces. IMPORTANCE The spread of foodborne viruses is likely associated with their adhesive nature. Virus attachment on food contact surfaces has been evaluated by quantitating virus recoveries from inoculated surfaces. This study aimed to evaluate the microenvironment in which nanometer-sized viruses interact with food contact surfaces and to compare the virus adhesion differences using AFM. The virus surrogate MS2 demonstrated less adhesion force to glass than to PVC via AFM, with the force-contributing factors including the intrinsic nature and the topography of the contact surfaces. This adhesion finding is consistent with the virus recoveries, which were determined indirectly. Greater numbers of viruses were recovered from glass than from PVC, after application at the same levels. The stronger MS2 adhesion onto PVC could be interrupted by incorporating a

  8. Interactive Multimedia Software on Fundamental Particles and Forces. Final Technical Report

    International Nuclear Information System (INIS)

    Jack Sculley

    1999-01-01

    Research in the SBIR Phase 2 grant number 95 ER 81944 centered on creating interactive multimedia software for teaching basic concepts in particle physics on fundamental particles and forces. The work was undertaken from February 1997 through July 1998. Overall the project has produced some very encouraging results in terms of product development, interest from the general public and interest from potential Phase 3 funders. Although the original Phase 3 publisher, McGraw Hill Home Interactive, was dissolved by its parent company, and other changes in the CD-ROM industry forced them to change their focus from CD-ROM to the Internet, there has been substantial interest from software publishers and online content providers in the content developed in the course of the Phase 2 research. Results are summarized

  9. Gauge unification of basic forces particularly of gravitation with strong interactions

    International Nuclear Information System (INIS)

    Salam, A.

    1977-01-01

    Corresponding to the two known types of gauge theories, Yang-Mills with spin-one mediating particles and Einstein Weyl with spin-two mediating particles, it is speculated that two distinct gauge unifications of the basic forces appear to be taking place. One is the familiar Yang-Mills unification of weak and electromagnetic forces with the strong. The second is the less familiar gauge unification of gravitation with spin-two tensor-dominated aspects of strong interactions. It is proposed that there are strongly interacting spin-two strong gravitons obeying Einstein's equations, and their existence gives a clue to an understanding of the (partial) confinement of quarks, as well as of the concept of hadronic temperature, through the use of Schwarzschild de-Sitter-like partially confining solitonic solutions of the strong gravity Einstein equation

  10. Near-field Light Scattering Techniques for Measuring Nanoparticle-Surface Interaction Energies and Forces.

    Science.gov (United States)

    Schein, Perry; Ashcroft, Colby K; O'Dell, Dakota; Adam, Ian S; DiPaolo, Brian; Sabharwal, Manit; Shi, Ce; Hart, Robert; Earhart, Christopher; Erickson, David

    2015-08-15

    Nanoparticles are quickly becoming commonplace in many commercial and industrial products, ranging from cosmetics to pharmaceuticals to medical diagnostics. Predicting the stability of the engineered nanoparticles within these products a priori remains an important and difficult challenge. Here we describe our techniques for measuring the mechanical interactions between nanoparticles and surfaces using near-field light scattering. Particle-surface interfacial forces are measured by optically "pushing" a particle against a reference surface and observing its motion using scattered near-field light. Unlike atomic force microscopy, this technique is not limited by thermal noise, but instead takes advantage of it. The integrated waveguide and microfluidic architecture allow for high-throughput measurements of about 1000 particles per hour. We characterize the reproducibility of and experimental uncertainty in the measurements made using the NanoTweezer surface instrument. We report surface interaction studies on gold nanoparticles with 50 nm diameters, smaller than previously reported in the literature using similar techniques.

  11. INTERACTIONS: DESIGN, IMPLEMENTATION AND EVALUATION OF A COMPUTATIONAL TOOL FOR TEACHING INTERMOLECULAR FORCES IN HIGHER EDUCATION

    Directory of Open Access Journals (Sweden)

    Francisco Geraldo Barbosa

    2015-12-01

    Full Text Available Intermolecular forces are a useful concept that can explain the attraction between particulate matter as well as numerous phenomena in our lives such as viscosity, solubility, drug interactions, and dyeing of fibers. However, studies show that students have difficulty understanding this important concept, which has led us to develop a free educational software in English and Portuguese. The software can be used interactively by teachers and students, thus facilitating better understanding. Professors and students, both graduate and undergraduate, were questioned about the software quality and its intuitiveness of use, facility of navigation, and pedagogical application using a Likert scale. The results led to the conclusion that the developed computer application can be characterized as an auxiliary tool to assist teachers in their lectures and students in their learning process of intermolecular forces.

  12. Interaction forces and conduction properties between multi wall carbon nanotube tips and Au(1 1 1)

    Energy Technology Data Exchange (ETDEWEB)

    Luna, M.; Pablo, P.J. de; Colchero, J.; Gomez-Herrero, J.; Baro, A.M.; Tokumoto, H.; Jarvis, S.P

    2003-07-15

    We have studied the interaction forces and electrical conduction properties arising between multiwall carbon nanotube tips and the Au(1 1 1) surface in air, by means of amplitude modulation scanning force microscopy, also called intermittent contact. We have centered our work on tips with metallic electronic structure and for the specific parameters used we have found a preliminary interaction range where there is no contact between tip and surface. Stable imaging in this non-contact range is possible with multiwall carbon nanotube tips. These tips have also been used to obtain simultaneous topographic and current maps of the surface. They show excellent properties as tips due to their high aspect ratio and durability, as a result of their elastic and non-reactive properties. Correspondingly, multiwall carbon nanotube tips allow high resolution local analysis of electrical conductivity on a nanometer scale.

  13. Concurrent Modeling of Hydrodynamics and Interaction Forces Improves Particle Deposition Predictions.

    Science.gov (United States)

    Jin, Chao; Ren, Carolyn L; Emelko, Monica B

    2016-04-19

    It is widely believed that media surface roughness enhances particle deposition-numerous, but inconsistent, examples of this effect have been reported. Here, a new mathematical framework describing the effects of hydrodynamics and interaction forces on particle deposition on rough spherical collectors in absence of an energy barrier was developed and validated. In addition to quantifying DLVO force, the model includes improved descriptions of flow field profiles and hydrodynamic retardation functions. This work demonstrates that hydrodynamic effects can significantly alter particle deposition relative to expectations when only the DLVO force is considered. Moreover, the combined effects of hydrodynamics and interaction forces on particle deposition on rough, spherical media are not additive, but synergistic. Notably, the developed model's particle deposition predictions are in closer agreement with experimental observations than those from current models, demonstrating the importance of inclusion of roughness impacts in particle deposition description/simulation. Consideration of hydrodynamic contributions to particle deposition may help to explain discrepancies between model-based expectations and experimental outcomes and improve descriptions of particle deposition during physicochemical filtration in systems with nonsmooth collector surfaces.

  14. Analytical modeling of soliton interactions in a nonlocal nonlinear medium analogous to gravitational force

    Science.gov (United States)

    Zeng, Shihao; Chen, Manna; Zhang, Ting; Hu, Wei; Guo, Qi; Lu, Daquan

    2018-01-01

    We illuminate an analytical model of soliton interactions in lead glass by analogizing to a gravitational force system. The orbits of spiraling solitons under a long-range interaction are given explicitly and demonstrated to follow Newton's second law of motion and the Binet equation by numerical simulations. The condition for circular orbits is obtained and the oscillating orbits are proved not to be closed. We prove the analogy between the nonlocal nonlinear optical system and gravitational system and specify the quantitative relation of the quantity between the two models.

  15. Three-quark forces and the role of meson exchanges in weak NN interaction

    International Nuclear Information System (INIS)

    Grach, I.; Shmatikov, M.

    1989-01-01

    The contribution of weak three-quark forces involving meson exchanges to the longitudinal analyzing power A L in the low-energy pp-scattering is calculated. The nonrelativistic potential model is used for the desorption of strong quark interactions while their weak coupling is described by the Weinberg-Salam lagrangian. The dominant mechanism of parity violation in the NN system (provided the one-pion exchange is forbidden by selection rules) is the contact interaction of quarks. 17 refs.; 3 figs

  16. Eutectic composite NiAl-Cr properties modeling based on interatomic interaction forces

    Science.gov (United States)

    Badamshin, I. Kh

    2018-03-01

    For new materials, information on the elasticity and strength characteristics necessary for calculating the stress-strain state of the turbine blades is limited. In these conditions, there is a need for theoretical methods for calculating the elastic and strength characteristics. The proposed theoretical methods are based on forces of interatomic interaction calculation. The classical methods based on the hypothesis of continuity do not allow calculating the material strength and thermophysical properties.

  17. Quantifying the human-robot interaction forces between a lower limb exoskeleton and healthy users.

    Science.gov (United States)

    Rathore, Ashish; Wilcox, Matthew; Ramirez, Dafne Zuleima Morgado; Loureiro, Rui; Carlson, Tom

    2016-08-01

    To counter the many disadvantages of prolonged wheelchair use, patients with spinal cord injuries (SCI) are beginning to turn towards robotic exoskeletons. However, we are currently unaware of the magnitude and distribution of forces acting between the user and the exoskeleton. This is a critical issue, as SCI patients have an increased susceptibility to skin lesions and pressure ulcer development. Therefore, we developed a real-time force measuring apparatus, which was placed at the physical human-robot interface (pHRI) of a lower limb robotic exoskeleton. Experiments captured the dynamics of these interaction forces whilst the participants performed a range of typical stepping actions. Our results indicate that peak forces occurred at the anterior aspect of both the left and right legs, areas that are particularly prone to pressure ulcer development. A significant difference was also found between the average force experienced at the anterior and posterior sensors of the right thigh during the swing phase for different movement primitives. These results call for the integration of instrumented straps as standard in lower limb exoskeletons. They also highlight the potential of such straps to be used as an alternative/complementary interface for the high-level control of lower limb exoskeletons in some patient groups.

  18. Simplified TiO2 force fields for studies of its interaction with biomolecules

    Science.gov (United States)

    Luan, Binquan; Huynh, Tien; Zhou, Ruhong

    2015-06-01

    Engineered TiO2 nanoparticles have been routinely applied in nanotechnology, as well as in cosmetics and food industries. Despite active experimental studies intended to clarify TiO2's biological effects, including potential toxicity, the relation between experimentally inferred nanotoxicity and industry standards for safely applying nanoparticles remains somewhat ambiguous with justified concerns. Supplemental to experiments, molecular dynamics simulations have proven to be efficacious in investigating the molecular mechanism of a biological process occurring at nanoscale. In this article, to facilitate the nanotoxicity and nanomedicine research related to this important metal oxide, we provide a simplified force field, based on the original Matsui-Akaogi force field but compatible to the Lennard-Jones potentials normally used in modeling biomolecules, for simulating TiO2 nanoparticles interacting with biomolecules. The force field parameters were tested in simulating the bulk structure of TiO2, TiO2 nanoparticle-water interaction, as well as the adsorption of proteins on the TiO2 nanoparticle. We demonstrate that these simulation results are consistent with experimental data/observations. We expect that simulations will help to better understand the interaction between TiO2 and molecules.

  19. 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.

  20. 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...

  1. Molecular interactions and residues involved in force generation in the T4 viral DNA packaging motor.

    Science.gov (United States)

    Migliori, Amy D; Smith, Douglas E; Arya, Gaurav

    2014-12-12

    Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. 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

  3. 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

  4. 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

  5. The Effects of Noncellulosic Compounds on the Nanoscale Interaction Forces Measured between Carbohydrate-Binding Module and Lignocellulosic Biomass.

    Science.gov (United States)

    Arslan, Baran; Colpan, Mert; Ju, Xiaohui; Zhang, Xiao; Kostyukova, Alla; Abu-Lail, Nehal I

    2016-05-09

    The lack of fundamental understanding of the types of forces that govern how cellulose-degrading enzymes interact with cellulosic and noncellulosic components of lignocellulosic surfaces limits the design of new strategies for efficient conversion of biomass to bioethanol. In a step to improve our fundamental understanding of such interactions, nanoscale forces acting between a model cellulase-a carbohydrate-binding module (CBM) of cellobiohydrolase I (CBH I)-and a set of lignocellulosic substrates with controlled composition were measured using atomic force microscopy (AFM). The three model substrates investigated were kraft (KP), sulfite (SP), and organosolv (OPP) pulped substrates. These substrates varied in their surface lignin coverage, lignin type, and xylan and acetone extractives' content. Our results indicated that the overall adhesion forces of biomass to CBM increased linearly with surface lignin coverage with kraft lignin showing the highest forces among lignin types investigated. When the overall adhesion forces were decoupled into specific and nonspecific component forces via the Poisson statistical model, hydrophobic and Lifshitz-van der Waals (LW) forces dominated the binding forces of CBM to kraft lignin, whereas permanent dipole-dipole interactions and electrostatic forces facilitated the interactions of lignosulfonates to CBM. Xylan and acetone extractives' content increased the attractive forces between CBM and lignin-free substrates, most likely through hydrogen bonding forces. When the substrates treated differently were compared, it was found that both the differences in specific and nonspecific forces between lignin-containing and lignin-free substrates were the least for OPP. Therefore, cellulase enzymes represented by CBM would weakly bind to organosolv lignin. This will facilitate an easy enzyme recovery compared to other substrates treated with kraft or sulfite pulping. Our results also suggest that altering the surface hydrophobicity

  6. Interactions of benzoic acid and phosphates with iron oxide colloids using chemical force titration.

    Science.gov (United States)

    Liang, Jana; Horton, J Hugh

    2005-11-08

    Colloidal iron oxides are an important component in soil systems and in water treatment processes. Humic-based organic compounds, containing both phenol and benzoate functional groups, are often present in these systems and compete strongly with phosphate species for binding sites on the iron oxide surfaces. Here, we examine the interaction of benzoate and phenolic groups with various iron oxide colloids using atomic force microscopy (AFM) chemical force titration measurements. Self-assembled monolayers (SAMs) of 4-(12-mercaptododecyloxy)benzoic acid and 4-(12-mercaptododecyloxy)phenol were used to prepare chemically modified Au-coated AFM tips, and these were used to probe the surface chemistry of a series of iron oxide colloids. The SAMs formed were also characterized using scanning tunneling microscopy, reflection-absorption infrared spectroscopy, and X-ray photoelectron spectroscopy. The surface pK(a) of 4-(12- mercaptododecyloxy)benzoic acid has been determined to be 4.0 +/- 0.5, and the interaction between the tip and the sample coated with a SAM of this species is dominated by hydrogen bonding. The chemical force titraton profile for an AFM probe coated with 4-(12- mercaptododecyloxy)benzoic acid and a bare iron oxide colloid demonstrates that the benzoic acid function group interacts with all three types of iron oxide sites present on the colloid surface over a wide pH range. Similar experiments were carried out on colloids precipitated in the presence of phosphoric, gallic, and tannic acids. The results are discussed in the context of the competitive binding interactions of solution species present in soils or in water treatment processes.

  7. 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.

  8. Extraction of user's navigation commands from upper body force interaction in walker assisted gait.

    Science.gov (United States)

    Frizera Neto, Anselmo; Gallego, Juan A; Rocon, Eduardo; Pons, José L; Ceres, Ramón

    2010-08-05

    The advances in technology make possible the incorporation of sensors and actuators in rollators, building safer robots and extending the use of walkers to a more diverse population. This paper presents a new method for the extraction of navigation related components from upper-body force interaction data in walker assisted gait. A filtering architecture is designed to cancel: (i) the high-frequency noise caused by vibrations on the walker's structure due to irregularities on the terrain or walker's wheels and (ii) the cadence related force components caused by user's trunk oscillations during gait. As a result, a third component related to user's navigation commands is distinguished. For the cancelation of high-frequency noise, a Benedict-Bordner g-h filter was designed presenting very low values for Kinematic Tracking Error ((2.035 +/- 0.358).10(-2) kgf) and delay ((1.897 +/- 0.3697).10(1)ms). A Fourier Linear Combiner filtering architecture was implemented for the adaptive attenuation of about 80% of the cadence related components' energy from force data. This was done without compromising the information contained in the frequencies close to such notch filters. The presented methodology offers an effective cancelation of the undesired components from force data, allowing the system to extract in real-time voluntary user's navigation commands. Based on this real-time identification of voluntary user's commands, a classical approach to the control architecture of the robotic walker is being developed, in order to obtain stable and safe user assisted locomotion.

  9. 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.

  10. Digital force-feedback for protein unfolding experiments using atomic force microscopy

    Science.gov (United States)

    Bippes, Christian A.; Janovjak, Harald; Kedrov, Alexej; Muller, Daniel J.

    2007-01-01

    Since its invention in the 1990s single-molecule force spectroscopy has been increasingly applied to study protein (un-)folding, cell adhesion, and ligand-receptor interactions. In most force spectroscopy studies, the cantilever of an atomic force microscope (AFM) is separated from a surface at a constant velocity, thus applying an increasing force to folded bio-molecules or bio-molecular bonds. Recently, Fernandez and co-workers introduced the so-called force-clamp technique. Single proteins were subjected to a defined constant force allowing their life times and life time distributions to be directly measured. Up to now, the force-clamping was performed by analogue PID controllers, which require complex additional hardware and might make it difficult to combine the force-feedback with other modes such as constant velocity. These points may be limiting the applicability and versatility of this technique. Here we present a simple, fast, and all-digital (software-based) PID controller that yields response times of a few milliseconds in combination with a commercial AFM. We demonstrate the performance of our feedback loop by force-clamp unfolding of single Ig27 domains of titin and the membrane proteins bacteriorhodopsin (BR) and the sodium/proton antiporter NhaA.

  11. Digital force-feedback for protein unfolding experiments using atomic force microscopy

    International Nuclear Information System (INIS)

    Bippes, Christian A; Janovjak, Harald; Kedrov, Alexej; Muller, Daniel J

    2007-01-01

    Since its invention in the 1990s single-molecule force spectroscopy has been increasingly applied to study protein (un-)folding, cell adhesion, and ligand-receptor interactions. In most force spectroscopy studies, the cantilever of an atomic force microscope (AFM) is separated from a surface at a constant velocity, thus applying an increasing force to folded bio-molecules or bio-molecular bonds. Recently, Fernandez and co-workers introduced the so-called force-clamp technique. Single proteins were subjected to a defined constant force allowing their life times and life time distributions to be directly measured. Up to now, the force-clamping was performed by analogue PID controllers, which require complex additional hardware and might make it difficult to combine the force-feedback with other modes such as constant velocity. These points may be limiting the applicability and versatility of this technique. Here we present a simple, fast, and all-digital (software-based) PID controller that yields response times of a few milliseconds in combination with a commercial AFM. We demonstrate the performance of our feedback loop by force-clamp unfolding of single Ig27 domains of titin and the membrane proteins bacteriorhodopsin (BR) and the sodium/proton antiporter NhaA

  12. An inverse method for determining the interaction force between the probe and sample using scanning near-field optical microscopy

    International Nuclear Information System (INIS)

    Chang, Win-Jin; Fang, Te-Hua

    2006-01-01

    This study proposes a means for calculating the interaction force during the scanning process using a scanning near-field optical microscope (SNOM) probe. The determination of the interaction force in the scanning system is regarded as an inverse vibration problem. The conjugate gradient method is applied to treat the inverse problem using available displacement measurements. The results show that the conjugate gradient method is less sensitive to measurement errors and prior information on the functional form of quality was not required. Furthermore, the initial guesses for the interaction force can be arbitrarily chosen for the iteration process

  13. Analysis of bit-rock interaction during stick-slip vibrations using PDC cutting force model

    Energy Technology Data Exchange (ETDEWEB)

    Patil, P.A.; Teodoriu, C. [Technische Univ. Clausthal, Clausthal-Zellerfeld (Germany). ITE

    2013-08-01

    Drillstring vibration is one of the limiting factors maximizing the drilling performance and also causes premature failure of drillstring components. Polycrystalline diamond compact (PDC) bit enhances the overall drilling performance giving the best rate of penetrations with less cost per foot but the PDC bits are more susceptible to the stick slip phenomena which results in high fluctuations of bit rotational speed. Based on the torsional drillstring model developed using Matlab/Simulink for analyzing the parametric influence on stick-slip vibrations due to drilling parameters and drillstring properties, the study of relations between weight on bit, torque on bit, bit speed, rate of penetration and friction coefficient have been analyzed. While drilling with the PDC bits, the bit-rock interaction has been characterized by cutting forces and the frictional forces. The torque on bit and the weight on bit have both the cutting component and the frictional component when resolved in horizontal and vertical direction. The paper considers that the bit is undergoing stick-slip vibrations while analyzing the bit-rock interaction of the PDC bit. The Matlab/Simulink bit-rock interaction model has been developed which gives the average cutting torque, T{sub c}, and friction torque, T{sub f}, values on cutters as well as corresponding average weight transferred by the cutting face, W{sub c}, and the wear flat face, W{sub f}, of the cutters value due to friction.

  14. Dissolved organic carbon--contaminant interaction descriptors found by 3D force field calculations.

    Science.gov (United States)

    Govers, H A J; Krop, H B; Parsons, J R; Tambach, T; Kubicki, J D

    2002-03-01

    Enthalpies of transfer at 300 K of various partitioning processes were calculated in order to study the suitability of 3D force fields for the calculation of partitioning constants. A 3D fulvic acid (FA) model of dissolved organic carbon (DOC) was built in a MM+ force field using AMI atomic charges and geometrical optimization (GO). 3,5-Dichlorobiphenyl (PCB14), 4,4'-dichlorobiphenyl (PCB15), 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane (PPDDT) and 2-chloro-4-ethylamino-6-isopropylamino-s-triazine (Atrazine) were inserted into different sites and their interaction energies with FA were calculated. Energies of hydration were calculated and subtracted from FA-contaminant interactions of selected sites. The resulting values for the enthalpies of transfer from water to DOC were 2.8, -1.4, -6.4 and 0.0 kcal/mol for PCB 14, PCB15, PPDDT and Atrazine, respectively. The value of PPDDT compared favorably with the experimental value of -5.0 kcal/mol. Prior to this, the method was studied by the calculation of the enthalpies of vaporization and aqueous solution using various force fields. In the MM + force field GO predicted enthalpies of vaporization deviated by +0.7 (PCB14), +3.6 (PCB15) and -0.7 (PPDDT)kcal/mol from experimental data, whereas enthalpies of aqueous solution deviated by -3.6 (PCB14), +5.8 (PCB15) and +3.7 (PPDDT) kcal/mol. Only for PCB14 the wrong sign of this enthalpy value was predicted. Potential advantages and limitations of the approach were discussed.

  15. Collapse and coexistence for a molecular braid with an attractive interaction component subject to mechanical forces.

    Science.gov (United States)

    Lee, Dominic J O'

    2015-04-15

    Dual mechanical braiding experiments provide a useful tool with which to investigate the nature of interactions between rod-like molecules, for instance actin and DNA. In conditions close to molecular condensation, one would expect an appearance of a local minimum in the interaction potential between the two molecules. We investigate this situation, introducing an attractive component into the interaction potential, using a model developed for describing such experiments. We consider both attractive interactions that do not depend on molecular structure and those which depend on a DNA-like helix structure. In braiding experiments, an attractive term may lead to certain effects. A local minimum may cause molecules to collapse from a loosely braided configuration into a tight one, occurring at a critical value of the moment applied about the axis of the braid. For a fixed number of braid pitches, this may lead to coexistence between the two braiding states, tight and loose. Coexistence implies certain proportions of the braid are in each state, their relative size depending on the number of braid pitches. This manifests itself as a linear dependence in numerically calculated quantities as functions of the number of braid pitches. Also, in the collapsed state, the braid radius stays roughly constant. Furthermore, if the attractive interaction is helix dependent, the left-right handed braid symmetry is broken. For a DNA like charge distribution, using the Kornyshev-Leikin interaction model, our results suggest that significant braid collapse and coexistence only occurs for left handed braids. Regardless of the interaction model, the study highlights the possible qualitative physics of braid collapse and coexistence; and the role helix specific forces might play, if important. The model could be used to connect other microscopic theories of interaction with braiding experiments.

  16. Collapse and coexistence for a molecular braid with an attractive interaction component subject to mechanical forces

    International Nuclear Information System (INIS)

    Lee, Dominic J

    2015-01-01

    Dual mechanical braiding experiments provide a useful tool with which to investigate the nature of interactions between rod-like molecules, for instance actin and DNA. In conditions close to molecular condensation, one would expect an appearance of a local minimum in the interaction potential between the two molecules. We investigate this situation, introducing an attractive component into the interaction potential, using a model developed for describing such experiments. We consider both attractive interactions that do not depend on molecular structure and those which depend on a DNA-like helix structure. In braiding experiments, an attractive term may lead to certain effects. A local minimum may cause molecules to collapse from a loosely braided configuration into a tight one, occurring at a critical value of the moment applied about the axis of the braid. For a fixed number of braid pitches, this may lead to coexistence between the two braiding states, tight and loose. Coexistence implies certain proportions of the braid are in each state, their relative size depending on the number of braid pitches. This manifests itself as a linear dependence in numerically calculated quantities as functions of the number of braid pitches. Also, in the collapsed state, the braid radius stays roughly constant. Furthermore, if the attractive interaction is helix dependent, the left-right handed braid symmetry is broken. For a DNA like charge distribution, using the Kornyshev–Leikin interaction model, our results suggest that significant braid collapse and coexistence only occurs for left handed braids. Regardless of the interaction model, the study highlights the possible qualitative physics of braid collapse and coexistence; and the role helix specific forces might play, if important. The model could be used to connect other microscopic theories of interaction with braiding experiments. (paper)

  17. The interaction of two collinear cracks in a rectangular superconductor slab under an electromagnetic force

    International Nuclear Information System (INIS)

    Gao Zhiwen; Zhou Youhe; Lee, Kang Yong

    2010-01-01

    The interaction of two collinear cracks is obtained for a type-II superconducting under electromagnetic force. Fracture analysis is performed by means of finite element method and the magnetic behavior of superconductor is described by the critical-state Bean model. The stress intensity factors at the crack tips can be obtained and discussed for decreasing field after zero-field cooling. It is revealed that the stress intensity factor decreases as applied field increases. The crack-tip stress intensity factors decrease when the distance between the two collinear cracks increases and the superconductors with smaller crack has more remarkable shielding effect than those with larger cracks.

  18. Tip-surface interactions at redox responsive poly(ferrocenylsilane) (PFS) interface by AFM-based force spectroscopy

    International Nuclear Information System (INIS)

    Chung Hongjing; Song Jing; Vancso, G. Julius

    2009-01-01

    Poly(ferrocenylsilanes) (PFS) belong to the class of redox responsive organometallic polymers. Atomic force microscopy (AFM)-based single molecule force spectroscopy (SMFS) was used earlier to study single chain PFS response and redox energy driven single chain PFS molecular motors. Here we present further AFM investigations of force interactions between tip and a grafted PFS surface under potential control in electrochemical redox cycles. Typical tip-Au interaction is considered as reference in the force measurements. First the electrostatic component in the diffused double layer (DL) in NaClO 4 electrolyte environment was considered for a 'grafted to' PFS, which dominated the interplay between the tip and sample surface. The DL forces can also hinder the physisorption of PFS chain onto the tip when the voltage was applied at -0.1 V. On the other hand, if the tip contacted the PFS surface prior to the electrochemical process, physisorption of PFS chains governed the overall interaction regardless of subsequently applied surface potential. In addition, prolonged contact time, t c , may also contribute to the stability of tip-PFS bridging and detection of electrostatic forces between the tip-PFS interface. The results showed that tip-substrate interaction forces without PFS grafts have negligibly small force contributions under similar, electrochemically controlled, conditions used in single PFS chain based molecular motors.

  19. Analysis of dispersive interactions at polymer/TiAlN interfaces by means of dynamic force spectroscopy.

    Science.gov (United States)

    Wiesing, M; de Los Arcos, T; Gebhard, M; Devi, A; Grundmeier, G

    2017-12-20

    The structural and electronic origins of the interactions between polycarbonate and sputter deposited TiAlN were analysed using a combined electron and force spectroscopic approach. Interaction forces were measured by means of dynamic force spectroscopy and the surface polarizability was analysed by X-ray photoelectron valence band spectroscopy. It could be shown that the adhesive interactions between polycarbonate and TiAlN are governed by van der Waals forces. Different surface cleansing and oxidizing treatments were investigated and the effect of the surface chemistry on the force interactions was analysed. Intense surface oxidation resulted in a decreased adhesion force by a factor of two due to the formation of a 2 nm thick Ti 0.21 Al 0.45 O surface oxide layer. The origin of the residual adhesion forces caused by the mixed Ti 0.21 Al 0.45 O surface oxide was clarified by considering the non-retarded Hamaker coefficients as calculated by Lifshitz theory, based on optical data from Reflection Electron Energy Loss Spectroscopy. This disclosed increased dispersion forces of Ti 0.21 Al 0.45 O due to the presence of Ti(iv) ions and related Ti 3d band optical transitions.

  20. Nanoparticle-nanoparticle interactions in biological media by Atomic Force Microscopy

    Science.gov (United States)

    Pyrgiotakis, Georgios; Blattmann, Christoph O.; Pratsinis, Sotiris; Demokritou, Philip

    2015-01-01

    Particle-particle interactions in physiological media are important determinants for nanoparticle fate and transport. Herein, such interactions are assessed by a novel Atomic Force Microscopy (AFM) based platform. Industry-relevant CeO2, Fe2O3, and SiO2 nanoparticles of various diameters were made by the flame spray pyrolysis (FSP) based Harvard Versatile Engineering Nanomaterials Generation System (Harvard VENGES). The nanoparticles were fully characterized structurally and morphologically and their properties in water and biological media were also assessed. The nanoparticles were attached on AFM tips and deposited on Si substrates to measure particle–particle interactions. The corresponding force was measured in air, water and biological media that are widely used in toxicological studies. The presented AFM based approach can be used to assess the agglomeration potential of nanoparticles in physiological fluids. The agglomeration potential of CeO2 nanoparticles in water and RPMI 1640 (Roswell Park Memorial Institute formulation 1640) was inversely proportional to their primary particle (PP) diameter, but for Fe2O3 nanoparticles, that potential is independent of PP diameter in these media. Moreover, in RPMI+10% Fetal Bovine Serum (FBS) the corona thickness and dispersibility of the CeO2 is independent of PP diameter while for Fe2O3, the corona thickness and dispersibility were inversely proportional to PP diameter. The present method can be combined with (dynamic light scattering (DLS), proteomics, and computer simulations to understand the nano-bio interactions, with emphasis on the agglomeration potential of nanoparticles and their transport in physiological media. PMID:23978039

  1. Propagation of the state change induced by external forces in local interactions

    Science.gov (United States)

    Lu, Jianjun; Tokinaga, Shozo

    2016-10-01

    This paper analyses the propagation of the state changes of agents that are induced by external forces applied to a plane. In addition, we propose two models for the behavior of the agents placed on a lattice plane, both of which are affected by local interactions. We first assume that agents are allowed to move to another site to maximise their satisfaction. Second, we utilise a model in which the agents choose activities on each site. The results show that the migration (activity) patterns of agents in both models achieve stability without any external forces. However, when we apply an impulsive external force to the state of the agents, we then observe the propagation of the changes in the agents' states. Using simulation studies, we show the conditions for the propagation of the state changes of the agents. We also show the propagation of the state changes of the agents allocated in scale-free networks and discuss the estimation of the agents' decisions in real state changes. Finally, we discuss the estimation of the agents' decisions in real state temporal changes using economic and social data from Japan and the United States.

  2. 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.

  3. Optical pulling and pushing forces exerted on silicon nanospheres with strong coherent interaction between electric and magnetic resonances.

    Science.gov (United States)

    Liu, Hongfeng; Panmai, Mingcheng; Peng, Yuanyuan; Lan, Sheng

    2017-05-29

    We investigated theoretically and numerically the optical pulling and pushing forces acting on silicon (Si) nanospheres (NSs) with strong coherent interaction between electric and magnetic resonances. We examined the optical pulling and pushing forces exerted on Si NSs by two interfering waves and revealed the underlying physical mechanism from the viewpoint of electric- and magnetic-dipole manipulation. As compared with a polystyrene (PS) NS, it was found that the optical pulling force for a Si NS with the same size is enlarged by nearly two orders of magnitude. In addition to the optical pulling force appearing at the long-wavelength side of the magnetic dipole resonance, very large optical pushing force is observed at the magnetic quadrupole resonance. The correlation between the optical pulling/pushing force and the directional scattering characterized by the ratio of the forward to backward scattering was revealed. More interestingly, it was found that the high-order electric and magnetic resonances in large Si NSs play an important role in producing optical pulling force which can be generated by not only s-polarized wave but also p-polarized one. Our finding indicates that the strong coherent interaction between the electric and magnetic resonances existing in nanoparticles with large refractive indices can be exploited to manipulate the optical force acting on them and the correlation between the optical force and the directional scattering can be used as guidance. The engineering and manipulation of optical forces will find potential applications in the trapping, transport and sorting of nanoparticles.

  4. Measuring cell viscoelastic properties using a force-spectrometer: influence of protein-cytoplasm interactions.

    Science.gov (United States)

    Canetta, Elisabetta; Duperray, Alain; Leyrat, Anne; Verdier, Claude

    2005-01-01

    Cell adhesive and rheological properties play a very important role in cell transmigration through the endothelial barrier, in particular in the case of inflammation (leukocytes) or cancer metastasis (cancer cells). In order to characterize cell viscoelastic properties, we have designed a force spectrometer (AFM) which can stretch cells thereby allowing measurement of their rheological properties. This custom-made force spectrometer allows two different visualizations, one lateral and one from below. It allows investigation of the effects of rheology involved during cell stretching. To test the ability of our system to characterize such viscoelastic properties, ICAM-1 transfected CHO cells were analyzed. Two forms of ICAM-1 were tested; wild type ICAM-1, which can interact with the cytoskeleton, and a mutant form which lacks the cytoplasmic domain, and is unable to associate with the cytoskeleton. Stretching experiments carried out on these cells show the formation of long filaments. Using a previous model of filament elongation, we could determine the viscoelastic properties of a single cell. As expected, different viscoelastic components were found between the wild type and the mutant, which reveal that the presence of interactions between ICAM-1 and the cytoskeleton increases the stiffness of the cell.

  5. G-mode magnetic force microscopy: Separating magnetic and electrostatic interactions using big data analytics

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Liam; Belianinov, Alex; Kalinin, Sergei V.; Jesse, Stephen [Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Institute for Functional Imaging of Materials, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Proksch, Roger [Asylum Research, An Oxford Instruments Company, Santa Barbara, California 93117 (United States); Zuo, Tingting [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Deptarment of Materials Science and Engineering, The University of Tennessee, Knoxville, Tennessee 37996-2200 (United States); Zhang, Yong [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Liaw, Peter K. [Deptarment of Materials Science and Engineering, The University of Tennessee, Knoxville, Tennessee 37996-2200 (United States)

    2016-05-09

    In this work, we develop a full information capture approach for Magnetic Force Microscopy (MFM), referred to as generalized mode (G-Mode) MFM. G-Mode MFM acquires and stores the full data stream from the photodetector, captured at sampling rates approaching the intrinsic photodiode limit. The data can be subsequently compressed, denoised, and analyzed, without information loss. Here, G-Mode MFM is implemented and compared to the traditional heterodyne-based MFM on model systems, including domain structures in ferromagnetic Yttrium Iron Garnet and the electronically and magnetically inhomogeneous high entropy alloy, CoFeMnNiSn. We investigate the use of information theory to mine the G-Mode MFM data and demonstrate its usefulness for extracting information which may be hidden in traditional MFM modes, including signatures of nonlinearities and mode-coupling phenomena. Finally, we demonstrate detection and separation of magnetic and electrostatic tip-sample interactions from a single G-Mode image, by analyzing the entire frequency response of the cantilever. G-Mode MFM is immediately implementable on any atomic force microscopy platform and as such is expected to be a useful technique for probing spatiotemporal cantilever dynamics and mapping material properties, as well as their mutual interactions.

  6. Visualising the Micro World of Chemical/Geochemical Interactions Using Atomic Force Microscopy (AFM)

    Energy Technology Data Exchange (ETDEWEB)

    Graham, G M; Sorbie, K S

    1997-12-31

    Scanning force microscopy, in particular AFM (Atomic Force Microscopy), provides a particular useful and interesting tool for the examination of surface structure at the near-atomic level. AFM is particularly well suited to the study of interactions at the surface in aqueous solutions using real time in-situ measurements. In this paper there is presented AFM images showing in situ crystal growth from supersaturated BaSO{sub 4} solutions onto the surface of barite. Growth structures in the form of spiral crystal growth features, presumably originating from screw dislocations, are illustrated. AFM images of novel scale crystal growth inhibition experiments are presented. Examination of the manner in which generically different species adsorb onto growth structures may help to explain mechanistic differences in the way which different inhibitor species perform against barium sulphate scale formation. Adsorption of polyacrylamide species onto mica surfaces have been viewed. The general utility of AFM to a number of other common surface interactions in oil field chemistry will be discussed. 17 refs., 3 figs.

  7. 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.

  8. Surface interaction forces of cellulose nanocrystals grafted with thermoresponsive polymer brushes.

    Science.gov (United States)

    Zoppe, Justin O; Osterberg, Monika; Venditti, Richard A; Laine, Janne; Rojas, Orlando J

    2011-07-11

    The colloidal stability and thermoresponsive behavior of poly(N-isopropylacrylamide) brushes grafted from cellulose nanocrystals (CNCs) of varying graft densities and molecular weights was investigated. Indication of the grafted polymer brushes was obtained after AFM imaging of CNCs adsorbed on silica. Also, aggregation of the nanoparticles carrying grafts of high degree of polymerization was observed. The responsiveness of grafted CNCs in aqueous dispersions and as an ultrathin film was evaluated by using light scattering, viscosimetry, and colloidal probe microscopy (CPM). Light transmittance measurements showed temperature-dependent aggregation originating from the different graft densities and molecular weights. The lower critical solution temperature (LCST) of grafted poly(NiPAAm) brushes was found to decrease with the ionic strength, as is the case for free poly(NiPAAm) in aqueous solution. Thermal responsive behavior of grafted CNCs in aqueous dispersions was observed by a sharp increase in dispersion viscosity as the temperature approached the LCST. CPM in liquid media for asymmetric systems consisting of ultrathin films of CNCs and a colloidal silica probe showed the distinctive effects of the grafted polymer brushes on interaction and adhesive forces. The origin of such forces was found to be mainly electrostatic and steric in the case of bare and grafted CNCs, respectively. A decrease in the onset of attractive and adhesion forces of grafted CNCs films were observed with the ionic strength of the aqueous solution. The decreased mobility of polymer brushes upon partial collapse and decreased availability of hydrogen bonding sites with higher electrolyte concentration were hypothesized as the main reasons for the less prominent polymer bridging between interacting surfaces.

  9. Extraction of user's navigation commands from upper body force interaction in walker assisted gait

    Directory of Open Access Journals (Sweden)

    Pons José L

    2010-08-01

    Full Text Available Abstract Background The advances in technology make possible the incorporation of sensors and actuators in rollators, building safer robots and extending the use of walkers to a more diverse population. This paper presents a new method for the extraction of navigation related components from upper-body force interaction data in walker assisted gait. A filtering architecture is designed to cancel: (i the high-frequency noise caused by vibrations on the walker's structure due to irregularities on the terrain or walker's wheels and (ii the cadence related force components caused by user's trunk oscillations during gait. As a result, a third component related to user's navigation commands is distinguished. Results For the cancelation of high-frequency noise, a Benedict-Bordner g-h filter was designed presenting very low values for Kinematic Tracking Error ((2.035 ± 0.358·10-2 kgf and delay ((1.897 ± 0.3697·101ms. A Fourier Linear Combiner filtering architecture was implemented for the adaptive attenuation of about 80% of the cadence related components' energy from force data. This was done without compromising the information contained in the frequencies close to such notch filters. Conclusions The presented methodology offers an effective cancelation of the undesired components from force data, allowing the system to extract in real-time voluntary user's navigation commands. Based on this real-time identification of voluntary user's commands, a classical approach to the control architecture of the robotic walker is being developed, in order to obtain stable and safe user assisted locomotion.

  10. Analytical Model of the Nonlinear Dynamics of Cantilever Tip-Sample Surface Interactions for Various Acoustic-Atomic Force Microscopies

    Science.gov (United States)

    Cantrell, John H., Jr.; Cantrell, Sean A.

    2008-01-01

    A comprehensive analytical model of the interaction of the cantilever tip of the atomic force microscope (AFM) with the sample surface is developed that accounts for the nonlinearity of the tip-surface interaction force. The interaction is modeled as a nonlinear spring coupled at opposite ends to linear springs representing cantilever and sample surface oscillators. The model leads to a pair of coupled nonlinear differential equations that are solved analytically using a standard iteration procedure. Solutions are obtained for the phase and amplitude signals generated by various acoustic-atomic force microscope (A-AFM) techniques including force modulation microscopy, atomic force acoustic microscopy, ultrasonic force microscopy, heterodyne force microscopy, resonant difference-frequency atomic force ultrasonic microscopy (RDF-AFUM), and the commonly used intermittent contact mode (TappingMode) generally available on AFMs. The solutions are used to obtain a quantitative measure of image contrast resulting from variations in the Young modulus of the sample for the amplitude and phase images generated by the A-AFM techniques. Application of the model to RDF-AFUM and intermittent soft contact phase images of LaRC-cp2 polyimide polymer is discussed. The model predicts variations in the Young modulus of the material of 24 percent from the RDF-AFUM image and 18 percent from the intermittent soft contact image. Both predictions are in good agreement with the literature value of 21 percent obtained from independent, macroscopic measurements of sheet polymer material.

  11. Reconstruction of the Tip-Surface Interaction Potential by Analysis of the Brownian Motion of an Atomic Force Microscope Tip

    NARCIS (Netherlands)

    Willemsen, O.H.; Kuipers, L.; van der Werf, Kees; de Grooth, B.G.; Greve, Jan

    2000-01-01

    The thermal movement of an atomic force microscope (AFM) tip is used to reconstruct the tip-surface interaction potential. If a tip is brought into the vicinity of a surface, its movement is governed by the sum of the harmonic cantilever potential and the tip-surface interaction potential. By

  12. An Atomic Force Microscopy Study of the Interactions Involving Polymers and Silane Networks

    Directory of Open Access Journals (Sweden)

    Rodrigo L. Oréfice

    1998-12-01

    Full Text Available ABSTRACT: Silane coupling agents have been frequently used as interfacial agents in polymer composites to improve interfacial strength and resistance to fluid migration. Although the capability of these agents in improving properties and performance of composites has been reported, there are still many uncertainties regarding the processing-structure-property relationships and the mechanisms of coupling developed by silane agents. In this work, an Atomic Force Microscope (AFM was used to measure interactions between polymers and silica substrates, where silane networks with a series of different structures were processed. The influence of the structure of silane networks on the interactions with polymers was studied and used to determine the mechanisms involved in the coupling phenomenon. The AFM results showed that phenomena such as chain penetration, entanglements, intersegment bonding, chain conformation in the vicinities of rigid surfaces were identified as being relevant for the overall processes of adhesion and adsorption of polymeric chains within a silane network. AFM adhesion curves showed that penetration of polymeric chains through a more open silane network can lead to higher levels of interactions between polymer and silane agents.

  13. Automated force volume image processing for biological samples.

    Directory of Open Access Journals (Sweden)

    Pavel Polyakov

    2011-04-01

    Full Text Available Atomic force microscopy (AFM has now become a powerful technique for investigating on a molecular level, surface forces, nanomechanical properties of deformable particles, biomolecular interactions, kinetics, and dynamic processes. This paper specifically focuses on the analysis of AFM force curves collected on biological systems, in particular, bacteria. The goal is to provide fully automated tools to achieve theoretical interpretation of force curves on the basis of adequate, available physical models. In this respect, we propose two algorithms, one for the processing of approach force curves and another for the quantitative analysis of retraction force curves. In the former, electrostatic interactions prior to contact between AFM probe and bacterium are accounted for and mechanical interactions operating after contact are described in terms of Hertz-Hooke formalism. Retraction force curves are analyzed on the basis of the Freely Jointed Chain model. For both algorithms, the quantitative reconstruction of force curves is based on the robust detection of critical points (jumps, changes of slope or changes of curvature which mark the transitions between the various relevant interactions taking place between the AFM tip and the studied sample during approach and retraction. Once the key regions of separation distance and indentation are detected, the physical parameters describing the relevant interactions operating in these regions are extracted making use of regression procedure for fitting experiments to theory. The flexibility, accuracy and strength of the algorithms are illustrated with the processing of two force-volume images, which collect a large set of approach and retraction curves measured on a single biological surface. For each force-volume image, several maps are generated, representing the spatial distribution of the searched physical parameters as estimated for each pixel of the force-volume image.

  14. 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).

  15. 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.

  16. van der Waals forces in density functional theory: Perturbational long-range electron-interaction corrections

    International Nuclear Information System (INIS)

    Angyan, Janos G.; Gerber, Iann C.; Savin, Andreas; Toulouse, Julien

    2005-01-01

    Long-range exchange and correlation effects, responsible for the failure of currently used approximate density functionals in describing van der Waals forces, are taken into account explicitly after a separation of the electron-electron interaction in the Hamiltonian into short- and long-range components. We propose a 'range-separated hybrid' functional based on a local density approximation for the short-range exchange-correlation energy, combined with a long-range exact exchange energy. Long-range correlation effects are added by a second-order perturbational treatment. The resulting scheme is general and is particularly well adapted to describe van der Waals complexes, such as rare gas dimers

  17. Minimal metabolic pathway structure is consistent with associated biomolecular interactions

    DEFF Research Database (Denmark)

    Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E.

    2014-01-01

    Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we......, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated....

  18. Biomolecular Interaction Study of Cyclolinopeptide A with Human Serum Albumin

    Directory of Open Access Journals (Sweden)

    Ben Rempel

    2010-01-01

    Full Text Available The kinetics, energetics, and structure of Cyclolinopeptide A binding with Human Serum Albumin were investigated with surface plasmon resonance and circular dichroism. The complex is formed through slow recognition kinetics that is temperature sensitive in the range of 20°C–37°C. The overall reaction was observed to be endothermic (ΔH=204 kJ mol−1 and entropy driven (ΔS=746 J mol−1K−1 with overall small changes to the tertiary structure.

  19. Interaction forces between nanoparticles in Lennard-Jones (L-J) solvents

    International Nuclear Information System (INIS)

    Sinha, Indrajit; Mukherjee, Ashim K

    2014-01-01

    Molecular simulations, such as Monte Carlo (MC) and molecular dynamics (MD) have been recently used for understanding the forces between colloidal nanoparticles that determine the dispersion and stability of nanoparticle suspensions. Herein we review the current status of research in the area of nanoparticles immersed in L-J solvents. The first study by Shinto et al. used large smooth spheres to depict nanoparticles in L-J and soft sphere solvents. The nanoparticles were held fixed at a particular interparticle distance and only the solvents were allowed to equilibrate. Both Van-der-waals and solvation forces were computed at different but fixed interparticle separation. Later Qin and Fitchthorn improved on this model by considering the nanoparticles as collection of molecules, thus taking into the account the effect of surface roughness of nanoparticles. Although the inter particle distance was fixed, the rotation of such nanoparticles with respect to each other was also investigated. Recently, in keeping with the experimental situation, we modified this model by allowing the nanoparticles to move and rotate freely. Solvophilic, neutral and solvophobic interactions between the solvent atoms and those that make up the nanoparticles were modelled. While neutral and solvophobic nanoparticles coalesce even at intermediate distances, solvophilic nanoparticles are more stable in solution due to the formation of a solvent shield

  20. Atomic force imaging microscopy investigation of the interaction of ultraviolet radiation with collagen thin films

    Science.gov (United States)

    Stylianou, A.; Yova, D.; Alexandratou, E.; Petri, A.

    2013-02-01

    Collagen is the major fibrous protein in the extracellular matrix and consists a significant component of skin, bone, cartilage and tendon. Due to its unique properties, it has been widely used as scaffold or culture substrate for tissue regeneration or/and cell-substrate interaction studies. The ultraviolet light-collagen interaction investigations are crucial for the improvement of many applications such as that of the UV irradiation in the field of biomaterials, as sterilizing and photo-cross-linking method. The aim of this paper was to investigate the mechanisms of UV-collagen interactions by developing a collagen-based, well characterized, surface with controlled topography of collagen thin films in the nanoscale range. The methodology was to quantify the collagen surface modification induced on ultraviolet radiation and correlate it with changes induced in cells. Surface nanoscale characterization was performed by Atomic Force Microscopy (AFM) which is a powerful tool and offers quantitative and qualitative information with a non-destructive manner. In order to investigate cells behavior, the irradiated films were used for in vitro cultivation of human skin fibroblasts and the cells morphology, migration and alignment were assessed with fluorescence microscopy imaging and image processing methods. The clarification of the effects of UV light on collagen thin films and the way of cells behavior to the different modifications that UV induced to the collagen-based surfaces will contribute to the better understanding of cell-matrix interactions in the nanoscale and will assist the appropriate use of UV light for developing biomaterials.

  1. Single-molecule imaging and manipulation of biomolecular machines and systems.

    Science.gov (United States)

    Iino, Ryota; Iida, Tatsuya; Nakamura, Akihiko; Saita, Ei-Ichiro; You, Huijuan; Sako, Yasushi

    2018-02-01

    Biological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration. We provide an overview of single-molecule imaging methods involving both small and large probes used to monitor the dynamic motions of molecular machines in vitro (purified proteins) and in living cells, and single-molecule manipulation methods used to measure the forces, mechanical properties and responses of biomolecules. We also introduce several examples of single-molecule analysis, focusing primarily on motor proteins and signal transduction systems. Single-molecule analysis is a powerful approach to unveil the operational mechanisms both of individual molecular machines and of systems consisting of many molecular machines. Quantitative, high-resolution single-molecule analyses of biomolecular systems at the various hierarchies of life will help to answer our fundamental question: "What is life?" 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.

  2. 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

  3. 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

  4. Improvements to the APBS biomolecular solvation software suite.

    Science.gov (United States)

    Jurrus, Elizabeth; Engel, Dave; Star, Keith; Monson, Kyle; Brandi, Juan; Felberg, Lisa E; Brookes, David H; Wilson, Leighton; Chen, Jiahui; Liles, Karina; Chun, Minju; Li, Peter; Gohara, David W; Dolinsky, Todd; Konecny, Robert; Koes, David R; Nielsen, Jens Erik; Head-Gordon, Teresa; Geng, Weihua; Krasny, Robert; Wei, Guo-Wei; Holst, Michael J; McCammon, J Andrew; Baker, Nathan A

    2018-01-01

    The Adaptive Poisson-Boltzmann Solver (APBS) software was developed to solve the equations of continuum electrostatics for large biomolecular assemblages that have provided impact in the study of a broad range of chemical, biological, and biomedical applications. APBS addresses the three key technology challenges for understanding solvation and electrostatics in biomedical applications: accurate and efficient models for biomolecular solvation and electrostatics, robust and scalable software for applying those theories to biomolecular systems, and mechanisms for sharing and analyzing biomolecular electrostatics data in the scientific community. To address new research applications and advancing computational capabilities, we have continually updated APBS and its suite of accompanying software since its release in 2001. In this article, we discuss the models and capabilities that have recently been implemented within the APBS software package including a Poisson-Boltzmann analytical and a semi-analytical solver, an optimized boundary element solver, a geometry-based geometric flow solvation model, a graph theory-based algorithm for determining pK a values, and an improved web-based visualization tool for viewing electrostatics. © 2017 The Protein Society.

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

    Science.gov (United States)

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

    2016-10-17

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

  6. 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

  7. A comprehensive modeling and vibration analysis of AFM microcantilevers subjected to nonlinear tip-sample interaction forces

    International Nuclear Information System (INIS)

    Eslami, Sohrab; Jalili, Nader

    2012-01-01

    Precise and accurate representation of an Atomic Force Microscopy (AFM) system is essential in studying the effects of boundary interaction forces present between the probe's tip and the sample. In this paper, a comprehensive analytical model for the AFM system utilizing a distributed-parameters based approach is proposed. More specifically, we consider two important attributes of these systems; namely the rotary inertia and shear deformation when compared with the Euler–Bernoulli beam theory. Moreover, a comprehensive nonlinear interaction force is assumed between probe's and sample in order to reveal the response of the system more realistically. This nanoscale interaction force is based on a general form consisting of both attractive and repulsive components as well as a function of the tip-sample distance and the microcantilever's base and sample oscillations. Mechanical properties of the sample could interact with the nanomechanical coupling field between the probe' tip and sample and be implemented in studying the composition information of the sample and the ultra-small features inside it. Therefore, by modulating the dynamics of the AFM system such as the driving amplitude of the microcantilever the procedure for the subsurface imaging is described. The presented approach here could be implemented for designing the AFM probes by examining the tip-sample interaction forces dominant by the van der Waals forces. Several numerical case studies are presented and the force–distance diagram reveals that the proposed nonlinear nanomechanical force along with the distributed-parameters model for the microcantilever is able to fulfill the mechanics of the Lennard–Jones potential. -- Highlights: ► We present a comprehensive distributed-parameters model for AFM microcantilever. ► Assuming a nonlinear and implicit interaction force between tip and sample. ► Timoshenko beam is compared with the Euler–Bernoulli having the same force model. ► Frequency

  8. Human-Human Interaction Forces and Interlimb Coordination During Side-by-Side Walking With Hand Contact.

    Science.gov (United States)

    Sylos-Labini, Francesca; d'Avella, Andrea; Lacquaniti, Francesco; Ivanenko, Yury

    2018-01-01

    Handholding can naturally occur between two walkers. When people walk side-by-side, either with or without hand contact, they often synchronize their steps. However, despite the importance of haptic interaction in general and the natural use of hand contact between humans during walking, few studies have investigated forces arising from physical interactions. Eight pairs of adult subjects participated in this study. They walked on side-by-side treadmills at 4 km/h independently and with hand contact. Only hand contact-related sensory information was available for unintentional synchronization, while visual and auditory communication was obstructed. Subjects walked at their natural cadences or following a metronome. Limb kinematics, hand contact 3D interaction forces and EMG activity of 12 upper limb muscles were recorded. Overall, unintentional step frequency locking was observed during about 40% of time in 88% of pairs walking with hand contact. On average, the amplitude of contact arm oscillations decreased while the contralateral (free) arm oscillated in the same way as during normal walking. Interestingly, EMG activity of the shoulder muscles of the contact arm did not decrease, and their synergistic pattern remained similar. The amplitude of interaction forces and of trunk oscillations was similar for synchronized and non-synchronized steps, though the synchronized steps were characterized by significantly more regular orientations of interaction forces. Our results further support the notion that gait synchronization during natural walking is common, and that it may occur through interaction forces. Conservation of the proximal muscle activity of the contact (not oscillating) arm is consistent with neural coupling between cervical and lumbosacral pattern generation circuitries ("quadrupedal" arm-leg coordination) during human gait. Overall, the findings suggest that individuals might integrate force interaction cues to communicate and coordinate steps during

  9. Human-Human Interaction Forces and Interlimb Coordination During Side-by-Side Walking With Hand Contact

    Directory of Open Access Journals (Sweden)

    Francesca Sylos-Labini

    2018-03-01

    Full Text Available Handholding can naturally occur between two walkers. When people walk side-by-side, either with or without hand contact, they often synchronize their steps. However, despite the importance of haptic interaction in general and the natural use of hand contact between humans during walking, few studies have investigated forces arising from physical interactions. Eight pairs of adult subjects participated in this study. They walked on side-by-side treadmills at 4 km/h independently and with hand contact. Only hand contact-related sensory information was available for unintentional synchronization, while visual and auditory communication was obstructed. Subjects walked at their natural cadences or following a metronome. Limb kinematics, hand contact 3D interaction forces and EMG activity of 12 upper limb muscles were recorded. Overall, unintentional step frequency locking was observed during about 40% of time in 88% of pairs walking with hand contact. On average, the amplitude of contact arm oscillations decreased while the contralateral (free arm oscillated in the same way as during normal walking. Interestingly, EMG activity of the shoulder muscles of the contact arm did not decrease, and their synergistic pattern remained similar. The amplitude of interaction forces and of trunk oscillations was similar for synchronized and non-synchronized steps, though the synchronized steps were characterized by significantly more regular orientations of interaction forces. Our results further support the notion that gait synchronization during natural walking is common, and that it may occur through interaction forces. Conservation of the proximal muscle activity of the contact (not oscillating arm is consistent with neural coupling between cervical and lumbosacral pattern generation circuitries (“quadrupedal” arm-leg coordination during human gait. Overall, the findings suggest that individuals might integrate force interaction cues to communicate and

  10. Analytic nuclear forces and molecular properties from full configuration interaction quantum Monte Carlo

    International Nuclear Information System (INIS)

    Thomas, Robert E.; Overy, Catherine; Opalka, Daniel; Alavi, Ali; Knowles, Peter J.; Booth, George H.

    2015-01-01

    Unbiased stochastic sampling of the one- and two-body reduced density matrices is achieved in full configuration interaction quantum Monte Carlo with the introduction of a second, “replica” ensemble of walkers, whose population evolves in imaginary time independently from the first and which entails only modest additional computational overheads. The matrices obtained from this approach are shown to be representative of full configuration-interaction quality and hence provide a realistic opportunity to achieve high-quality results for a range of properties whose operators do not necessarily commute with the Hamiltonian. A density-matrix formulated quasi-variational energy estimator having been already proposed and investigated, the present work extends the scope of the theory to take in studies of analytic nuclear forces, molecular dipole moments, and polarisabilities, with extensive comparison to exact results where possible. These new results confirm the suitability of the sampling technique and, where sufficiently large basis sets are available, achieve close agreement with experimental values, expanding the scope of the method to new areas of investigation

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Yongbin Chang

    2011-09-01

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

  13. Subatomic forces

    International Nuclear Information System (INIS)

    Sutton, C.

    1989-01-01

    Inside the atom, particles interact through two forces which are never felt in the everyday world. But they may hold the key to the Universe. These ideas on subatomic forces are discussed with respect to the strong force, the electromagnetic force and the electroweak force. (author)

  14. Interactions between fluvial forces and vegetation size, density and morphology influence plant mortality during experimental floods

    Science.gov (United States)

    Stella, J. C.; Kui, L.; Manners, R.; Wilcox, A. C.; Lightbody, A.; Sklar, L. S.

    2015-12-01

    Introduction and methods Fluvial disturbance is a key driver of riparian vegetation dynamics in river corridors. Despite an increasing understanding of ecohydraulic interactions between plants and fluvial forces, the interactive influences of plant morphology and sediment supply on plant mortality, a key demographic factor, are largely unknown. To better understand these processes, we designed and conducted a series of flume experiments to: (1) quantify effects of plant traits that interact with flow and sediment transport on plant loss to scour during floods; and (2) predict plant dislodgement for different species across a range of plant sizes, patch densities, and sediment condition (equilibrium transport versus sediment deficit). We ran ten experimental floods in a 28 m long × 0.6 m wide × 0.71 m tall flume, using live, 1-3 year-old tamarisk and cottonwood seedlings with contrasting morphologies with varied combinations of size and density. Results and discussion Both sediment supply and plant traits (morphology and composition) have significant impacts on plant vulnerability during floods. Sediment deficit resulted in bed degradation and a 35% greater risk of plant loss compared to equilibrium sediment conditions. The probability of plant dislodgement in sparse patches was 4.5 times greater than in dense patches. Tamarisk plants and patches had greater frontal area, basal diameter and longer roots compared to cottonwood across all seedling heights. These traits, as well as its lower crown position reduced tamarisk's vulnerability to scour by 75%. Compared with cottonwood, tamarisk exhibits better resistance to floods, due to its greater root biomass and longer roots that stabilize soil, and its greater frontal area and lower crown that effectively trap sediment. These traits likely contribute to riverscape-scale changes in channel morphology that are evident where tamarisk has invaded native riparian communities, and explain the persistence of tamarisk

  15. A new force field including charge directionality for TMAO in aqueous solution

    International Nuclear Information System (INIS)

    Usui, Kota; Nagata, Yuki; Hunger, Johannes; Bonn, Mischa; Sulpizi, Marialore

    2016-01-01

    We propose a new force field for trimethylamine N-oxide (TMAO), which is designed to reproduce the long-lived and highly directional hydrogen bond between the TMAO oxygen (O TMAO ) atom and surrounding water molecules. Based on the data obtained by ab initio molecular dynamics simulations, we introduce three dummy sites around O TMAO to mimic the O TMAO lone pairs and we migrate the negative charge on the O TMAO to the dummy sites. The force field model developed here improves both structural and dynamical properties of aqueous TMAO solutions. Moreover, it reproduces the experimentally observed dependence of viscosity upon increasing TMAO concentration quantitatively. The simple procedure of the force field construction makes it easy to implement in molecular dynamics simulation packages and makes it compatible with the existing biomolecular force fields. This paves the path for further investigation of protein-TMAO interaction in aqueous solutions.

  16. A new force field including charge directionality for TMAO in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Usui, Kota; Nagata, Yuki, E-mail: sulpizi@uni-mainz.de, E-mail: nagata@mpip-mainz.mpg.de; Hunger, Johannes; Bonn, Mischa [Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz (Germany); Sulpizi, Marialore, E-mail: sulpizi@uni-mainz.de, E-mail: nagata@mpip-mainz.mpg.de [Johannes Gutenberg University Mainz, Staudingerweg 7, 55099 Mainz (Germany)

    2016-08-14

    We propose a new force field for trimethylamine N-oxide (TMAO), which is designed to reproduce the long-lived and highly directional hydrogen bond between the TMAO oxygen (O{sub TMAO}) atom and surrounding water molecules. Based on the data obtained by ab initio molecular dynamics simulations, we introduce three dummy sites around O{sub TMAO} to mimic the O{sub TMAO} lone pairs and we migrate the negative charge on the O{sub TMAO} to the dummy sites. The force field model developed here improves both structural and dynamical properties of aqueous TMAO solutions. Moreover, it reproduces the experimentally observed dependence of viscosity upon increasing TMAO concentration quantitatively. The simple procedure of the force field construction makes it easy to implement in molecular dynamics simulation packages and makes it compatible with the existing biomolecular force fields. This paves the path for further investigation of protein-TMAO interaction in aqueous solutions.

  17. Clustering biomolecular complexes by residue contacts similarity

    NARCIS (Netherlands)

    Garcia Lopes Maia Rodrigues, João; Trellet, Mikaël; Schmitz, Christophe; Kastritis, Panagiotis; Karaca, Ezgi; Melquiond, Adrien S J; Bonvin, Alexandre M J J; Garcia Lopes Maia Rodrigues, João

    Inaccuracies in computational molecular modeling methods are often counterweighed by brute-force generation of a plethora of putative solutions. These are then typically sieved via structural clustering based on similarity measures such as the root mean square deviation (RMSD) of atomic positions.

  18. Single molecule force spectroscopy: methods and applications in biology

    International Nuclear Information System (INIS)

    Shen Yi; Hu Jun

    2012-01-01

    Single molecule measurements have transformed our view of biomolecules. Owing to the ability of monitoring the activity of individual molecules, we now see them as uniquely structured, fluctuating molecules that stochastically transition between frequently many substrates, as two molecules do not follow precisely the same trajectory. Indeed, it is this discovery of critical yet short-lived substrates that were often missed in ensemble measurements that has perhaps contributed most to the better understanding of biomolecular functioning resulting from single molecule experiments. In this paper, we give a review on the three major techniques of single molecule force spectroscopy, and their applications especially in biology. The single molecular study of biotin-streptavidin interactions is introduced as a successful example. The problems and prospects of the single molecule force spectroscopy are discussed, too. (authors)

  19. Quantitative modeling assesses the contribution of bond strengthening, rebinding and force sharing to the avidity of biomolecule interactions.

    Directory of Open Access Journals (Sweden)

    Valentina Lo Schiavo

    Full Text Available Cell adhesion is mediated by numerous membrane receptors. It is desirable to derive the outcome of a cell-surface encounter from the molecular properties of interacting receptors and ligands. However, conventional parameters such as affinity or kinetic constants are often insufficient to account for receptor efficiency. Avidity is a qualitative concept frequently used to describe biomolecule interactions: this includes incompletely defined properties such as the capacity to form multivalent attachments. The aim of this study is to produce a working description of monovalent attachments formed by a model system, then to measure and interpret the behavior of divalent attachments under force. We investigated attachments between antibody-coated microspheres and surfaces coated with sparse monomeric or dimeric ligands. When bonds were subjected to a pulling force, they exhibited both a force-dependent dissociation consistent with Bell's empirical formula and a force- and time-dependent strengthening well described by a single parameter. Divalent attachments were stronger and less dependent on forces than monovalent ones. The proportion of divalent attachments resisting a force of 30 piconewtons for at least 5 s was 3.7 fold higher than that of monovalent attachments. Quantitative modeling showed that this required rebinding, i.e. additional bond formation between surfaces linked by divalent receptors forming only one bond. Further, experimental data were compatible with but did not require stress sharing between bonds within divalent attachments. Thus many ligand-receptor interactions do not behave as single-step reactions in the millisecond to second timescale. Rather, they exhibit progressive stabilization. This explains the high efficiency of multimerized or clustered receptors even when bonds are only subjected to moderate forces. Our approach provides a quantitative way of relating binding avidity to measurable parameters including bond

  20. Quantitative Modeling Assesses the Contribution of Bond Strengthening, Rebinding and Force Sharing to the Avidity of Biomolecule Interactions

    Science.gov (United States)

    Lo Schiavo, Valentina; Robert, Philippe; Limozin, Laurent; Bongrand, Pierre

    2012-01-01

    Cell adhesion is mediated by numerous membrane receptors. It is desirable to derive the outcome of a cell-surface encounter from the molecular properties of interacting receptors and ligands. However, conventional parameters such as affinity or kinetic constants are often insufficient to account for receptor efficiency. Avidity is a qualitative concept frequently used to describe biomolecule interactions: this includes incompletely defined properties such as the capacity to form multivalent attachments. The aim of this study is to produce a working description of monovalent attachments formed by a model system, then to measure and interpret the behavior of divalent attachments under force. We investigated attachments between antibody-coated microspheres and surfaces coated with sparse monomeric or dimeric ligands. When bonds were subjected to a pulling force, they exhibited both a force-dependent dissociation consistent with Bell’s empirical formula and a force- and time-dependent strengthening well described by a single parameter. Divalent attachments were stronger and less dependent on forces than monovalent ones. The proportion of divalent attachments resisting a force of 30 piconewtons for at least 5 s was 3.7 fold higher than that of monovalent attachments. Quantitative modeling showed that this required rebinding, i.e. additional bond formation between surfaces linked by divalent receptors forming only one bond. Further, experimental data were compatible with but did not require stress sharing between bonds within divalent attachments. Thus many ligand-receptor interactions do not behave as single-step reactions in the millisecond to second timescale. Rather, they exhibit progressive stabilization. This explains the high efficiency of multimerized or clustered receptors even when bonds are only subjected to moderate forces. Our approach provides a quantitative way of relating binding avidity to measurable parameters including bond maturation, rebinding and

  1. 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

  2. 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.

  3. Modes of Escherichia coli Dps Interaction with DNA as Revealed by Atomic Force Microscopy.

    Directory of Open Access Journals (Sweden)

    Vladislav V Melekhov

    Full Text Available Multifunctional protein Dps plays an important role in iron assimilation and a crucial role in bacterial genome packaging. Its monomers form dodecameric spherical particles accumulating ~400 molecules of oxidized iron ions within the protein cavity and applying a flexible N-terminal ends of each subunit for interaction with DNA. Deposition of iron is a well-studied process by which cells remove toxic Fe2+ ions from the genetic material and store them in an easily accessible form. However, the mode of interaction with linear DNA remained mysterious and binary complexes with Dps have not been characterized so far. It is widely believed that Dps binds DNA without any sequence or structural preferences but several lines of evidence have demonstrated its ability to differentiate gene expression, which assumes certain specificity. Here we show that Dps has a different affinity for the two DNA fragments taken from the dps gene regulatory region. We found by atomic force microscopy that Dps predominantly occupies thermodynamically unstable ends of linear double-stranded DNA fragments and has high affinity to the central part of the branched DNA molecule self-assembled from three single-stranded oligonucleotides. It was proposed that Dps prefers binding to those regions in DNA that provide more contact pads for the triad of its DNA-binding bundle associated with one vertex of the protein globule. To our knowledge, this is the first study revealed the nucleoid protein with an affinity to branched DNA typical for genomic regions with direct and inverted repeats. As a ubiquitous feature of bacterial and eukaryotic genomes, such structural elements should be of particular care, but the protein system evolutionarily adapted for this function is not yet known, and we suggest Dps as a putative component of this system.

  4. Probing the nanoscale interaction forces and elastic properties of organic and inorganic materials using force-distance (F-D) spectroscopy

    Science.gov (United States)

    Vincent, Abhilash

    Due to their therapeutic applications such as radical scavenging, MRI contrast imaging, Photoluminescence imaging, drug delivery, etc., nanoparticles (NPs) have a significant importance in bio-nanotechnology. The reason that prevents the utilizing NPs for drug delivery in medical field is mostly due to their biocompatibility issues (incompatibility can lead to toxicity and cell death). Changes in the surface conditions of NPs often lead to NP cytotoxicity. Investigating the role of NP surface properties (surface charges and surface chemistry) on their interactions with biomolecules (Cells, protein and DNA) could enhance the current understanding of NP cytotoxicity. Hence, it is highly beneficial to the nanotechnology community to bring more attention towards the enhancement of surface properties of NPs to make them more biocompatible and less toxic to biological systems. Surface functionalization of NPs using specific ligand biomolecules have shown to enhance the protein adsorption and cellular uptake through more favorable interaction pathways. Cerium oxide NPs (CNPs also known as nanoceria) are potential antioxidants in cell culture models and understanding the nature of interaction between cerium oxide NPs and biological proteins and cells are important due to their therapeutic application (especially in site specific drug delivery systems). The surface charges and surface chemistry of CNPs play a major role in protein adsorption and cellular uptake. Hence, by tuning the surface charges and by selecting proper functional molecules on the surface, CNPs exhibiting strong adhesion to biological materials can be prepared. By probing the nanoscale interaction forces acting between CNPs and protein molecules using Atomic Force Microscopy (AFM) based force-distance (F-D) spectroscopy, the mechanism of CNP-protein adsorption and CNP cellular uptake can be understood more quantitatively. The work presented in this dissertation is based on the application of AFM in

  5. Interaction of Volcanic Forcing and El Nino: Sensitivity to the Eruption Magnitude and El Nino Intensity

    KAUST Repository

    Predybaylo, Evgeniya

    2015-04-01

    Volcanic aerosols formed in the stratosphere after strong explosive eruptions influence Earth\\'s radiative balance, affecting atmospheric and oceanic temperatures and circulation. It was observed that the recent volcanic eruptions frequently occurred in El Nino years. Analysis of the paleo data confirms that the probability of a sequent El Nino occurrence after the eruption increases. To better understand the physical mechanism of this interaction we employed ocean-atmosphere coupled climate model CM2.1, developed in the Geophysical Fluid Dynamics Laboratory, and conducted a series of numerical experiments using initial conditions with different El Nino Southern Oscillation (ENSO) strengths forced by volcanic eruptions of different magnitudes, Pinatubo of June 1991 and Tambora of April 1815: (i) strong ENSO/Pinatubo, (ii) weak ENSO/Pinatubo, (iii) strong ENSO/Tambora. The amount of ejected material from the Tambora eruption was about three times greater than that of the Pinatubo eruption. The initial conditions with El Nino were sampled from the CM2.1 long control run. Our simulations show the enhancement of El Nino in the second year after an eruption. We found that the spatial-temporal structure of model responses is sensitive to both the magnitude of an eruption and the strength of El Nino. We analyzed the ocean dynamic in the tropical Pacific for all cases to uncover the physical mechanism, resulting in the enhanced and/or prolonged El Nino.

  6. Interaction of Volcanic Forcing and El Nino: Sensitivity to the Eruption Magnitude and El Nino Intensity

    KAUST Repository

    Predybaylo, Evgeniya; Wittenberg, Andrew; Stenchikov, Georgiy L.

    2015-01-01

    Volcanic aerosols formed in the stratosphere after strong explosive eruptions influence Earth's radiative balance, affecting atmospheric and oceanic temperatures and circulation. It was observed that the recent volcanic eruptions frequently occurred in El Nino years. Analysis of the paleo data confirms that the probability of a sequent El Nino occurrence after the eruption increases. To better understand the physical mechanism of this interaction we employed ocean-atmosphere coupled climate model CM2.1, developed in the Geophysical Fluid Dynamics Laboratory, and conducted a series of numerical experiments using initial conditions with different El Nino Southern Oscillation (ENSO) strengths forced by volcanic eruptions of different magnitudes, Pinatubo of June 1991 and Tambora of April 1815: (i) strong ENSO/Pinatubo, (ii) weak ENSO/Pinatubo, (iii) strong ENSO/Tambora. The amount of ejected material from the Tambora eruption was about three times greater than that of the Pinatubo eruption. The initial conditions with El Nino were sampled from the CM2.1 long control run. Our simulations show the enhancement of El Nino in the second year after an eruption. We found that the spatial-temporal structure of model responses is sensitive to both the magnitude of an eruption and the strength of El Nino. We analyzed the ocean dynamic in the tropical Pacific for all cases to uncover the physical mechanism, resulting in the enhanced and/or prolonged El Nino.

  7. Interaction forces model on a bubble growing for nuclear best estimate computer codes

    International Nuclear Information System (INIS)

    Espinosa-Paredes, Gilberto; Nunez-Carrera, Alejandro; Martinez-Mendez, Elizabeth J.

    2005-01-01

    This paper presents a mathematical model that takes into account the bubble radius variation that take place in a boiling water nuclear reactor during transients with changes in the pressure vessel, changes in the inlet core mass flow rate, density-wave phenomena or flow regime instability. The model with expansion effects was developed considering the interaction force between a dilute dispersion of gas bubbles and a continuous liquid phase. The closure relationships were formulated as an associated problem with the spatial deviation around averaging variables as a function of known variables. In order to solve the closure problem, a geometric model given by an eccentric unit cell was applied as an approach of heterogeneous structure of the two-phase flow. The closure relationship includes additional terms that represent combined effects between translation and pulsation due to displacement and size variation of the bubbles, respectively. This result can be implanted straightforward in best estimate thermo-hydraulics models. An example, the implementation of the closure relationships into TRAC best estimate computer code is presented

  8. Thermal characterization of static and dynamical properties of the confined molecular systems interacting through dispersion force.

    Science.gov (United States)

    Ramos, Sergio Luis L M; Ogino, Michihiko; Oguni, Masaharu

    2015-01-28

    We investigated the thermal properties of liquid methylcyclohexane and racemic sec-butylcyclohexane, as representatives of a molecular system with only dispersion-force intermolecular interactions, confined in the pores (thickness/diameter d = 12, 6, 1.1 nm) of silica gels by adiabatic calorimetry. The results imply a heterogeneous picture for molecular aggregate under confinement consisting of an interfacial region and an inner pore one. In the vicinity of a glass-transition temperature T(g,bulk) of bulk liquid, two distinguishable relaxation phenomena were observed for the confined systems and their origins were attributed to the devitrification, namely glass transition, processes of (1) a layer of interfacial molecules adjacent to the pore walls and (2) the molecules located in the middle of the pore. A third glass-transition phenomenon was observed at lower temperatures and ascribed to a secondary relaxation process. The glass transition of the interfacial-layer molecules was found to proceed at temperatures rather above T(g,bulk), whereas that of the molecules located in the inner pore region occurred at temperatures below T(g,bulk). We discuss the reason why the molecules located in different places in the pores reveal the respectively different dynamical properties.

  9. MDM2-MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance.

    Science.gov (United States)

    Moscetti, Ilaria; Teveroni, Emanuela; Moretti, Fabiola; Bizzarri, Anna Rita; Cannistraro, Salvatore

    Murine double minute 2 (MDM2) and 4 (MDM4) are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2-MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2-MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD ) in the micromolar range for the MDM2-MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2-MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2-MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation.

  10. Insights into the Interactions of Amino Acids and Peptides with Inorganic Materials Using Single-Molecule Force Spectroscopy.

    Science.gov (United States)

    Das, Priyadip; Duanias-Assaf, Tal; Reches, Meital

    2017-03-06

    The interactions between proteins or peptides and inorganic materials lead to several interesting processes. For example, combining proteins with minerals leads to the formation of composite materials with unique properties. In addition, the undesirable process of biofouling is initiated by the adsorption of biomolecules, mainly proteins, on surfaces. This organic layer is an adhesion layer for bacteria and allows them to interact with the surface. Understanding the fundamental forces that govern the interactions at the organic-inorganic interface is therefore important for many areas of research and could lead to the design of new materials for optical, mechanical and biomedical applications. This paper demonstrates a single-molecule force spectroscopy technique that utilizes an AFM to measure the adhesion force between either peptides or amino acids and well-defined inorganic surfaces. This technique involves a protocol for attaching the biomolecule to the AFM tip through a covalent flexible linker and single-molecule force spectroscopy measurements by atomic force microscope. In addition, an analysis of these measurements is included.

  11. Quantification of the Interaction Forces between Metals and Graphene by Quantum Chemical Calculations and Dynamic Force Measurements under Ambient Conditions

    Czech Academy of Sciences Publication Activity Database

    Lazar, P.; Zhang, S.; Šafářová, K.; LI, Q.; Froning, J. P.; Granatier, Jaroslav; Hobza, Pavel; Zbořil, R.; Besenbacher, F.; Dong, M.; Otyepka, M.

    2013-01-01

    Roč. 7, č. 2 (2013), s. 1646-1651 ISSN 1936-0851 R&D Projects: GA ČR GBP208/12/G016 Grant - others:European Regional Development Fund(XE) CZ.1.05/2.1.00/03.0058; GA MŠk(CZ) EE2.3.20.0017 Program:EE Institutional support: RVO:61388963 Keywords : graphene * nanoparticle * interaction energy * gold * platinum * copper Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 12.033, year: 2013

  12. Single Molecule Science for Personalized Nanomedicine: Atomic Force Microscopy of Biopolymer-Protein Interactions

    Science.gov (United States)

    Hsueh, Carlin

    Nanotechnology has a unique and relatively untapped utility in the fields of medicine and dentistry at the level of single-biopolymer and -molecule diagnostics. In recent years atomic force microscopy (AFM) has garnered much interest due to its ability to obtain atomic-resolution of molecular structures and probe biophysical behaviors of biopolymers and proteins in a variety of biologically significant environments. The work presented in this thesis focuses on the nanoscale manipulation and observation of biopolymers to develop an innovative technology for personalized medicine while understanding complex biological systems. These studies described here primarily use AFM to observe biopolymer interactions with proteins and its surroundings with unprecedented resolution, providing a better understanding of these systems and interactions at the nanoscale. Transcriptional profiling, the measure of messenger RNA (mRNA) abundance in a single cell, is a powerful technique that detects "behavior" or "symptoms" at the tissue and cellular level. We have sought to develop an alternative approach, using our expertise in AFM and single molecule nanotechnology, to achieve a cost-effective high throughput method for sensitive detection and profiling of subtle changes in transcript abundance. The technique does not require amplification of the mRNA sample because the AFM provides three-dimensional views of molecules with unprecedented resolution, requires minimal sample preparation, and utilizes a simple tagging chemistry on cDNA molecules. AFM images showed collagen polymers in teeth and of Drebrin-A remodeling of filamentous actin structure and mechanics. AFM was used to image collagen on exposed dentine tubules and confirmed tubule occlusion with a desensitizing prophylaxis paste by Colgate-Palmolive. The AFM also superseded other microscopy tools in resolving F-actin helix remodeling and possible cooperative binding by a neuronal actin binding protein---Drebrin-A, an

  13. Imaging contrast and tip-sample interaction of non-contact amplitude modulation atomic force microscopy with Q -control

    International Nuclear Information System (INIS)

    Shi, Shuai; Guo, Dan; Luo, Jianbin

    2017-01-01

    Active quality factor ( Q ) exhibits many promising properties in dynamic atomic force microscopy. Energy dissipation and image contrasts are investigated in the non-contact amplitude modulation atomic force microscopy (AM-AFM) with an active Q -control circuit in the ambient air environment. Dissipated power and virial were calculated to compare the highly nonlinear interaction of tip-sample and image contrasts with different Q gain values. Greater free amplitudes and lower effective Q values show better contrasts for the same setpoint ratio. Active quality factor also can be employed to change tip-sample interaction force in non-contact regime. It is meaningful that non-destructive and better contrast images can be realized in non-contact AM-AFM by applying an active Q -control to the dynamic system. (paper)

  14. The effect of including tensor forces in nucleon-nucleon interaction on three-nucleon binding energy

    International Nuclear Information System (INIS)

    Osman, A.; Ramadan, S.

    1986-01-01

    Separable two-body interactions are used in considering the three-nucleon problem. The nucleon-nucleon potentials are taken to include attraction and repulsion as well as tensor forces. The separable approximation is used in order to investigate the effect of the tensor forces. The separable expansion is introduced in the three-nucleon problem, by which the Faddeev equations are reduced to a well-behaved set of coupled integral equations. Numerical calculations are carried out for the obtained integral equations using potential functions of the Yamaguchi, Gaussian, Takabin, Mongan and Reid forms. The present calculated values of the binding energies of the 3 H and 3 He nuclei are in good agreement with the experimental values. The effect of including the tensor forces in the nucleon-nucleon interactions is found to improve the three-nucleon binding energy by about 4.490% to 8.324%. 37 refs., 2 tabs. (author)

  15. Toward the description of electrostatic interactions between globular proteins: potential of mean force in the primitive model.

    Science.gov (United States)

    Dahirel, Vincent; Jardat, Marie; Dufrêche, Jean-François; Turq, Pierre

    2007-09-07

    Monte Carlo simulations are used to calculate the exact potential of mean force between charged globular proteins in aqueous solution. The aim of the present paper is to study the influence of the ions of the added salt on the effective interaction between these nanoparticles. The charges of the model proteins, either identical or opposite, are either central or distributed on a discrete pattern. Contrarily to Poisson-Boltzmann predictions, attractive, and repulsive direct forces between proteins are not screened similarly. Moreover, it has been shown that the relative orientations of the charge patterns strongly influence salt-mediated interactions. More precisely, for short distances between the proteins, ions enhance the difference of the effective forces between (i) like-charged and oppositely charged proteins, (ii) attractive and repulsive relative orientations of the proteins, which may affect the selectivity of protein/protein recognition. Finally, such results observed with the simplest models are applied to a more elaborate one to demonstrate their generality.

  16. Fundamental investigation on interaction forces in bubble swarms and its application to the design of centrifugal separators

    International Nuclear Information System (INIS)

    Wisman, R.

    1979-01-01

    The present investigation deals with two aspects of gas-liquid flows, viz. interaction forces between the phases in bubble swarms and numerical description of rotating gas-liquid flows. The insight obtained was applied to the development of axial gas-liquid cyclones, as used i.a. as primary separators in nuclear boiling water reactors. (Auth.)

  17. Multiscale modeling of interaction of alane clusters on Al(111) surfaces : a reactive force field and infrared absorbtion spectroscopy approach

    NARCIS (Netherlands)

    Ojwang, J.G.O.; Chaudhuri, S.; Duin, van A.C.T.; Chabal, Y.J.; Veyan, J.-F.; Santen, van R.A.; Kramer, G.J.; Goddard III, W.A.

    2010-01-01

    We have used reactive force field (ReaxFF) to investigate the mechanism of interaction of alanes on Al(111) surface. Our simulations show that, on the Al(111) surface, alanes oligomerize into larger alanes. In addition, from our simulations, adsorption of atomic hydrogen on Al(111) surface leads to

  18. Quantification of the Force of Nanoparticle-Cell Membrane Interactions and Its Influence on Intracellular Trafficking of Nanoparticles

    Science.gov (United States)

    Vasir, Jaspreet K.; Labhasetwar, Vinod

    2008-01-01

    Understanding the interaction of nanoparticles (NPs) with the cell membrane and their trafficking through cells is imperative to fully explore the use of NPs for efficient intracellular delivery of therapeutics. Here, we report a novel method of measuring the force of NP-cell membrane interactions using atomic force microscopy (AFM). Poly(dl-lactide co-glycolide, PLGA) NPs functionalized with poly-l-lysine were used as a model system, to demonstrate that this force determines the adhesive interaction of NPs with the cell membrane and in turn the extent of cellular uptake of NPs, and hence that of the encapsulated therapeutic. Cellular uptake of NPs was monitored using AFM imaging, and the dynamics of their intracellular distribution was quantified using confocal microscopy. Results demonstrated that the functionalized NPs have a five-fold greater force of adhesion with the cell membrane and the time-lapse AFM images show their rapid internalization than unmodified NPs. The intracellular trafficking study showed that the functionalized NPs escape more rapidly and efficiently from late endosomes than unmodified NPs and result in 10-fold higher intracellular delivery of the encapsulated model protein. The findings described herein enhance our basic understanding of the NP-cell membrane interaction on the basis of physical phenomena that could have wider applications in developing efficient nanocarrier systems for intracellular delivery of therapeutics. PMID:18692238

  19. The ABC (Analysing Biomolecular Contacts-database

    Directory of Open Access Journals (Sweden)

    Walter Peter

    2007-03-01

    Full Text Available As protein-protein interactions are one of the basic mechanisms in most cellular processes, it is desirable to understand the molecular details of protein-protein contacts and ultimately be able to predict which proteins interact. Interface areas on a protein surface that are involved in protein interactions exhibit certain characteristics. Therefore, several attempts were made to distinguish protein interactions from each other and to categorize them. One way of classification are the groups of transient and permanent interactions. Previously two of the authors analysed several properties for transient complexes such as the amino acid and secondary structure element composition and pairing preferences. Certainly, interfaces can be characterized by many more possible attributes and this is a subject of intense ongoing research. Although several freely available online databases exist that illuminate various aspects of protein-protein interactions, we decided to construct a new database collecting all desired interface features allowing for facile selection of subsets of complexes. As database-server we applied MySQL and the program logic was written in JAVA. Furthermore several class extensions and tools such as JMOL were included to visualize the interfaces and JfreeChart for the representation of diagrams and statistics. The contact data is automatically generated from standard PDB files by a tcl/tk-script running through the molecular visualization package VMD. Currently the database contains 536 interfaces extracted from 479 PDB files and it can be queried by various types of parameters. Here, we describe the database design and demonstrate its usefulness with a number of selected features.

  20. 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.

  1. 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.

  2. Application of the nuclear field theory to monopole interactions which include all the vertices of a general force

    International Nuclear Information System (INIS)

    Bes, D.R.; Dussel, G.G.; Liotta, R.J.; Sofia, H.M.; Broglia, R.A.

    1976-01-01

    The field treatment is applied to the monopole pairing and monopole particle-hole interactions in a two-level model. All the vertices of realistic interactions appear, and the problems treated here have most of the complexities of real nuclei. Yet, the model remains sufficiently simple, so that a close comparison with the results of a (conventional) treatment in which only the fermion degrees of freedom are considered is possible. The applicability to actual physical situations appears to be feasible, both for schematic or realistic forces. The advantage of including the exchange components of the interaction in the construction of the phonon is discussed. (Auth.)

  3. 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.

  4. Interaction between benzenedithiolate and gold: Classical force field for chemical bonding

    Science.gov (United States)

    Leng, Yongsheng; Krstić, Predrag S.; Wells, Jack C.; Cummings, Peter T.; Dean, David J.

    2005-06-01

    We have constructed a group of classical potentials based on ab initio density-functional theory (DFT) calculations to describe the chemical bonding between benzenedithiolate (BDT) molecule and gold atoms, including bond stretching, bond angle bending, and dihedral angle torsion involved at the interface between the molecule and gold clusters. Three DFT functionals, local-density approximation (LDA), PBE0, and X3LYP, have been implemented to calculate single point energies (SPE) for a large number of molecular configurations of BDT-1, 2 Au complexes. The three DFT methods yield similar bonding curves. The variations of atomic charges from Mulliken population analysis within the molecule/metal complex versus different molecular configurations have been investigated in detail. We found that, except for bonded atoms in BDT-1, 2 Au complexes, the Mulliken partial charges of other atoms in BDT are quite stable, which significantly reduces the uncertainty in partial charge selections in classical molecular simulations. Molecular-dynamics (MD) simulations are performed to investigate the structure of BDT self-assembled monolayer (SAM) and the adsorption geometry of S adatoms on Au (111) surface. We found that the bond-stretching potential is the most dominant part in chemical bonding. Whereas the local bonding geometry of BDT molecular configuration may depend on the DFT functional used, the global packing structure of BDT SAM is quite independent of DFT functional, even though the uncertainty of some force-field parameters for chemical bonding can be as large as ˜100%. This indicates that the intermolecular interactions play a dominant role in determining the BDT SAMs global packing structure.

  5. 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.

  6. Casimir interaction between a cylinder and a plate at finite temperature: Exact results and comparison to proximity force approximation

    International Nuclear Information System (INIS)

    Teo, L. P.

    2011-01-01

    We study the finite temperature Casimir interaction between a cylinder and a plate using the exact formula derived from the Matsubara representation and the functional determinant representation. We consider the scalar field with Dirichlet and Neumann boundary conditions. The asymptotic expansions of the Casimir free energy and the Casimir force when the separation a between the cylinder and the plate is small are derived. As in the zero temperature case, it is found that the leading terms of the Casimir free energy and the Casimir force agree with those derived from the proximity force approximation when rT>>1, where r is the radius of the cylinder. Specifically, when aT 5/2 whereas, for the Casimir force, it is of order T 7/2 . In this case, the leading terms are independent of the separation a. When 1 3/2 , whereas, for the force, it is inversely proportional to a 5/2 . The first order corrections to the proximity force approximations in different temperature regions are computed using the perturbation approach. In the zero temperature case, the results agree with those derived in [M. Bordag, Phys. Rev. D 73, 125018 (2006)].

  7. 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.

  8. 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.

  9. Salt bridge interactions within the β2 integrin α7 helix mediate force-induced binding and shear resistance ability.

    Science.gov (United States)

    Zhang, Xiao; Li, Linda; Li, Ning; Shu, Xinyu; Zhou, Lüwen; Lü, Shouqin; Chen, Shenbao; Mao, Debin; Long, Mian

    2018-01-01

    The functional performance of the αI domain α 7 helix in β 2 integrin activation depends on the allostery of the α 7 helix, which axially slides down; therefore, it is critical to elucidate what factors regulate the allostery. In this study, we determined that there were two conservative salt bridge interaction pairs that constrain both the upper and bottom ends of the α 7 helix. Molecular dynamics (MD) simulations for three β 2 integrin members, lymphocyte function-associated antigen-1 (LFA-1; α L β 2 ), macrophage-1 antigen (Mac-1; α M β 2 ) and α x β 2 , indicated that the magnitude of the salt bridge interaction is related to the stability of the αI domain and the strength of the corresponding force-induced allostery. The disruption of the salt bridge interaction, especially with double mutations in both salt bridges, significantly reduced the force-induced allostery time for all three members. The effects of salt bridge interactions of the αI domain α 7 helix on β 2 integrin conformational stability and allostery were experimentally validated using Mac-1 constructs. The results demonstrated that salt bridge mutations did not alter the conformational state of Mac-1, but they did increase the force-induced ligand binding and shear resistance ability, which was consistent with MD simulations. This study offers new insight into the importance of salt bridge interaction constraints of the αI domain α 7 helix and external force for β 2 integrin function. © 2017 Federation of European Biochemical Societies.

  10. The role of the ion-molecule and molecule-molecule interactions in the formation of the two-ion average force interaction potential

    CERN Document Server

    Ajrian, E A; Sidorenko, S N

    2002-01-01

    The effect of the ion-molecule and intermolecular interactions on the formation of inter-ion average force potentials is investigated within the framework of a classical ion-dipole model of electrolyte solutions. These potentials are shown to possess the Coulomb asymptotics at large distances while in the region of mean distances they reveal creation and disintegration of solvent-shared ion pairs. The calculation results provide a qualitatively authentic physical picture which is experimentally observed in strong electrolytes solutions. In particular, an increased interaction between an ion and a molecule enhances formation of ion pairs in which the ions are separated by one solvent molecule

  11. Surface Forces Apparatus measurements of interactions between rough and reactive calcite surfaces.

    Science.gov (United States)

    Dziadkowiec, Joanna; Javadi, Shaghayegh; Bratvold, Jon Einar; Nilsen, Ola; Røyne, Anja

    2018-05-28

    Nm-range forces acting between calcite surfaces in water affect macroscopic properties of carbonate rocks and calcite-based granular materials, and are significantly influenced by calcite surface recrystallization. We suggest that the repulsive mechanical effects related to nm-scale surface recrystallization of calcite in water could be partially responsible for the observed decrease of cohesion in calcitic rocks saturated with water. Using the Surface Forces Apparatus (SFA), we simultaneously followed the calcite reactivity and measured the forces in water in two surface configurations: between two rough calcite surfaces (CC), or between rough calcite and a smooth mica surface (CM). We used nm-scale rough, polycrystalline calcite films prepared by Atomic Layer Deposition (ALD). We measured only repulsive forces in CC in CaCO 3 -saturated water, which was related to roughness and possibly to repulsive hydration effects. Adhesive or repulsive forces were measured in CM in CaCO 3 -saturated water depending on calcite roughness, and the adhesion was likely enhanced by electrostatic effects. The pull-off adhesive force in CM became stronger with time and this increase was correlated with a decrease of roughness at contacts, which parameter could be estimated from the measured force-distance curves. That suggested a progressive increase of real contact areas between the surfaces, caused by gradual pressure-driven deformation of calcite surface asperities during repeated loading-unloading cycles. Reactivity of calcite was affected by mass transport across nm to µm-thick gaps between the surfaces. Major roughening was observed only for the smoothest calcite films, where gaps between two opposing surfaces were nm-thick over µm-sized areas, and led to force of crystallization that could overcome confining pressures of the order of MPa. Any substantial roughening of calcite caused a significant increase of the repulsive mechanical force contribution.

  12. Biomolecular Characterization of Putative Antidiabetic Herbal Extracts

    Science.gov (United States)

    Stadlbauer, Verena; Haselgrübler, Renate; Lanzerstorfer, Peter; Plochberger, Birgit; Borgmann, Daniela; Jacak, Jaroslaw; Winkler, Stephan M.; Schröder, Klaus; Höglinger, Otmar; Weghuber, Julian

    2016-01-01

    Induction of GLUT4 translocation in the absence of insulin is considered a key concept to decrease elevated blood glucose levels in diabetics. Due to the lack of pharmaceuticals that specifically increase the uptake of glucose from the blood circuit, application of natural compounds might be an alternative strategy. However, the effects and mechanisms of action remain unknown for many of those substances. For this study we investigated extracts prepared from seven different plants, which have been reported to exhibit anti-diabetic effects, for their GLUT4 translocation inducing properties. Quantitation of GLUT4 translocation was determined by total internal reflection fluorescence (TIRF) microscopy in insulin sensitive CHO-K1 cells and adipocytes. Two extracts prepared from purslane (Portulaca oleracea) and tindora (Coccinia grandis) were found to induce GLUT4 translocation, accompanied by an increase of intracellular glucose concentrations. Our results indicate that the PI3K pathway is mainly responsible for the respective translocation process. Atomic force microscopy was used to prove complete plasma membrane insertion. Furthermore, this approach suggested a compound mediated distribution of GLUT4 molecules in the plasma membrane similar to insulin stimulated conditions. Utilizing a fluorescent actin marker, TIRF measurements indicated an impact of purslane and tindora on actin remodeling as observed in insulin treated cells. Finally, in-ovo experiments suggested a significant reduction of blood glucose levels under tindora and purslane treated conditions in a living organism. In conclusion, this study confirms the anti-diabetic properties of tindora and purslane, which stimulate GLUT4 translocation in an insulin-like manner. PMID:26820984

  13. 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.

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

    Science.gov (United States)

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

    2013-10-08

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

  15. Nonsmooth Newton method for Fischer function reformulation of contact force problems for interactive rigid body simulation

    DEFF Research Database (Denmark)

    Silcowitz, Morten; Niebe, Sarah Maria; Erleben, Kenny

    2009-01-01

    contact response. In this paper, we present a new approach to contact force determination. We reformulate the contact force problem as a nonlinear root search problem, using a Fischer function. We solve this problem using a generalized Newton method. Our new Fischer - Newton method shows improved...... qualities for specific configurations where the most widespread alternative, the Projected Gauss-Seidel method, fails. Experiments show superior convergence properties of the exact Fischer - Newton method....

  16. Vibrotactile Compliance Feedback for Tangential Force Interaction.

    Science.gov (United States)

    Heo, Seongkook; Lee, Geehyuk

    2017-01-01

    This paper presents a method to generate a haptic illusion of compliance using a vibrotactile actuator when a tangential force is applied to a rigid surface. The novel method builds on a conceptual compliance model where a physical object moves on a textured surface in response to a tangential force. The method plays vibration patterns simulating friction-induced vibrations as an applied tangential force changes. We built a prototype consisting of a two-dimensional tangential force sensor and a surface transducer to test the effectiveness of the model. Participants in user experiments with the prototype perceived the rigid surface of the prototype as a moving, rubber-like plate. The main findings of the experiments are: 1) the perceived stiffness of a simulated material can be controlled by controlling the force-playback transfer function, 2) its perceptual properties such as softness and pleasantness can be controlled by changing friction grain parameters, and 3) the use of the vibrotactile compliance feedback reduces participants' workload including physical demand and frustration while performing a force repetition task.

  17. Flight Dynamics of Flexible Aircraft with Aeroelastic and Inertial Force Interactions

    Science.gov (United States)

    Nguyen, Nhan T.; Tuzcu, Ilhan

    2009-01-01

    This paper presents an integrated flight dynamic modeling method for flexible aircraft that captures coupled physics effects due to inertial forces, aeroelasticity, and propulsive forces that are normally present in flight. The present approach formulates the coupled flight dynamics using a structural dynamic modeling method that describes the elasticity of a flexible, twisted, swept wing using an equivalent beam-rod model. The structural dynamic model allows for three types of wing elastic motion: flapwise bending, chordwise bending, and torsion. Inertial force coupling with the wing elasticity is formulated to account for aircraft acceleration. The structural deflections create an effective aeroelastic angle of attack that affects the rigid-body motion of flexible aircraft. The aeroelastic effect contributes to aerodynamic damping forces that can influence aerodynamic stability. For wing-mounted engines, wing flexibility can cause the propulsive forces and moments to couple with the wing elastic motion. The integrated flight dynamics for a flexible aircraft are formulated by including generalized coordinate variables associated with the aeroelastic-propulsive forces and moments in the standard state-space form for six degree-of-freedom flight dynamics. A computational structural model for a generic transport aircraft has been created. The eigenvalue analysis is performed to compute aeroelastic frequencies and aerodynamic damping. The results will be used to construct an integrated flight dynamic model of a flexible generic transport aircraft.

  18. Resonance energy transfer (RET)-Induced intermolecular pairing force: a tunable weak interaction and its application in SWNT separation.

    Science.gov (United States)

    Pan, Xiaoyong; Chen, Hui; Wang, Wei Zhi; Ng, Siu Choon; Chan-Park, Mary B

    2011-07-21

    This paper explores evidence of an optically mediated interaction that is active in the separation mechanism of certain selective agents through consideration of the contrasting selective behaviors of two conjugated polymers with distinct optical properties. The involvement of a RET-induced intermolecular pairing force is implied by the different illumination response behaviors. The magnitude of this interaction scales with the external stimulus parameter, the illumination irradiance (I), and thus is tunable. This suggests a facile technique to modify the selectivity of polymers toward specific SWNT species by altering the polymer structure to adjust the corresponding intermolecular interaction. This is the first experimental verification and application of a RET-induced intermolecular pairing force to SWNT separation. With this kind of interaction taken into account, reasonable interpretation of some conflicting data, especially PLE maps, can be easily made. The above conclusion can be applied to other substances as long as they are electrically neutral and there is photon-induced RET between them. The significant magnitude of this interaction makes direct manipulation of molecules/particles possible and is expected to have applications in molecular engineering. © 2011 American Chemical Society

  19. Modelling the effects of the radiation reaction force on the interaction of thin foils with ultra-intense laser fields

    Science.gov (United States)

    Duff, M. J.; Capdessus, R.; Del Sorbo, D.; Ridgers, C. P.; King, M.; McKenna, P.

    2018-06-01

    The effects of the radiation reaction (RR) force on thin foils undergoing radiation pressure acceleration (RPA) are investigated. Using QED-particle-in-cell simulations, the influence of the RR force on the collective electron dynamics within the target can be examined. The magnitude of the RR force is found to be strongly dependent on the target thickness, leading to effects which can be observed on a macroscopic scale, such as changes to the distribution of the emitted radiation and the target dynamics. This suggests that such parameters may be controlled in experiments at multi-PW laser facilities. In addition, the effects of the RR force are characterized in terms of an average radiation emission angle. We present an analytical model which, for the first time, describes the effect of the RR force on the collective electron dynamics within the ‘light-sail’ regime of RPA. The predictions of this model can be tested in future experiments with ultra-high intensity lasers interacting with solid targets.

  20. 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...

  1. 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.

  2. On contribution of three-body forces to Nd interaction at intermediate energies

    International Nuclear Information System (INIS)

    Uzikov, Yu.N.

    2001-01-01

    Available data on large-angle nucleon-deuteron elastic scattering Nd → dN below the pion threshold give a signal for three-body forces. There is a problem of separation of possible subtle aspects of these forces from off-shell effects in two-nucleon potentials. By considering the main mechanisms of the process Nd → dN, we show qualitatively that in the quasi-binary reaction N + d → (NN) + N with the final spin singlet NN-pair in the S-state the relative contribution of the 3N forces differs substantially from the elastic channel. It gives a new testing ground for the problem in question

  3. Human-Robot Interaction: Does Robotic Guidance Force Affect Gait-Related Brain Dynamics during Robot-Assisted Treadmill Walking?

    Directory of Open Access Journals (Sweden)

    Kristel Knaepen

    Full Text Available In order to determine optimal training parameters for robot-assisted treadmill walking, it is essential to understand how a robotic device interacts with its wearer, and thus, how parameter settings of the device affect locomotor control. The aim of this study was to assess the effect of different levels of guidance force during robot-assisted treadmill walking on cortical activity. Eighteen healthy subjects walked at 2 km.h-1 on a treadmill with and without assistance of the Lokomat robotic gait orthosis. Event-related spectral perturbations and changes in power spectral density were investigated during unassisted treadmill walking as well as during robot-assisted treadmill walking at 30%, 60% and 100% guidance force (with 0% body weight support. Clustering of independent components revealed three clusters of activity in the sensorimotor cortex during treadmill walking and robot-assisted treadmill walking in healthy subjects. These clusters demonstrated gait-related spectral modulations in the mu, beta and low gamma bands over the sensorimotor cortex related to specific phases of the gait cycle. Moreover, mu and beta rhythms were suppressed in the right primary sensory cortex during treadmill walking compared to robot-assisted treadmill walking with 100% guidance force, indicating significantly larger involvement of the sensorimotor area during treadmill walking compared to robot-assisted treadmill walking. Only marginal differences in the spectral power of the mu, beta and low gamma bands could be identified between robot-assisted treadmill walking with different levels of guidance force. From these results it can be concluded that a high level of guidance force (i.e., 100% guidance force and thus a less active participation during locomotion should be avoided during robot-assisted treadmill walking. This will optimize the involvement of the sensorimotor cortex which is known to be crucial for motor learning.

  4. Human-Robot Interaction: Does Robotic Guidance Force Affect Gait-Related Brain Dynamics during Robot-Assisted Treadmill Walking?

    Science.gov (United States)

    Knaepen, Kristel; Mierau, Andreas; Swinnen, Eva; Fernandez Tellez, Helio; Michielsen, Marc; Kerckhofs, Eric; Lefeber, Dirk; Meeusen, Romain

    2015-01-01

    In order to determine optimal training parameters for robot-assisted treadmill walking, it is essential to understand how a robotic device interacts with its wearer, and thus, how parameter settings of the device affect locomotor control. The aim of this study was to assess the effect of different levels of guidance force during robot-assisted treadmill walking on cortical activity. Eighteen healthy subjects walked at 2 km.h-1 on a treadmill with and without assistance of the Lokomat robotic gait orthosis. Event-related spectral perturbations and changes in power spectral density were investigated during unassisted treadmill walking as well as during robot-assisted treadmill walking at 30%, 60% and 100% guidance force (with 0% body weight support). Clustering of independent components revealed three clusters of activity in the sensorimotor cortex during treadmill walking and robot-assisted treadmill walking in healthy subjects. These clusters demonstrated gait-related spectral modulations in the mu, beta and low gamma bands over the sensorimotor cortex related to specific phases of the gait cycle. Moreover, mu and beta rhythms were suppressed in the right primary sensory cortex during treadmill walking compared to robot-assisted treadmill walking with 100% guidance force, indicating significantly larger involvement of the sensorimotor area during treadmill walking compared to robot-assisted treadmill walking. Only marginal differences in the spectral power of the mu, beta and low gamma bands could be identified between robot-assisted treadmill walking with different levels of guidance force. From these results it can be concluded that a high level of guidance force (i.e., 100% guidance force) and thus a less active participation during locomotion should be avoided during robot-assisted treadmill walking. This will optimize the involvement of the sensorimotor cortex which is known to be crucial for motor learning.

  5. Effect of different crystal faces on experimental interaction force and aggregation of hematite

    NARCIS (Netherlands)

    Hiemstra, T.; Riemsdijk, van W.H.

    1999-01-01

    Charging is a basic property of the solid/solution interface of minerals. The charging at different crystal faces depends on the surface chemical composition, that is, the type and number of proton-reactive surface groups. Atomic force microscopy has provided direct information on the pH-dependent

  6. Mechanism of interaction between cellulase action and applied shear force, an hypothesis

    NARCIS (Netherlands)

    Lenting, H.B.M.; Lenting, H.B.M.; Warmoeskerken, Marinus

    2001-01-01

    An overview is given of what is known in literature concerning the structure of both cellulose and cellulase enzymes and the enzymatic degradation of cellulose. Based on this knowledge, a hypothesis is formulated about the relation between cellulase performance and required applied shear force on

  7. Methodes de calcul des forces aerodynamiques pour les etudes des interactions aeroservoelastiques

    Science.gov (United States)

    Biskri, Djallel Eddine

    L'aeroservoelasticite est un domaine ou interagissent la structure flexible d'un avion, l'aerodynamique et la commande de vol. De son cote, la commande du vol considere l'avion comme une structure rigide et etudie l'influence du systeme de commande sur la dynamique de vol. Dans cette these, nous avons code trois nouvelles methodes d'approximation de forces aerodynamiques: Moindres carres corriges, Etat minimal corrige et Etats combines. Dans les deux premieres methodes, les erreurs d'approximation entre les forces aerodynamiques approximees par les methodes classiques et celles obtenues par les nouvelles methodes ont les memes formes analytiques que celles des forces aerodynamiques calculees par LS ou MS. Quant a la troisieme methode, celle-ci combine les formulations des forces approximees avec les methodes standards LS et MS. Les vitesses et frequences de battement et les temps d'executions calcules par les nouvelles methodes versus ceux calcules par les methodes classiques ont ete analyses.

  8. The compensatory interaction between motor unit firing behavior and muscle force during fatigue.

    Science.gov (United States)

    Contessa, Paola; De Luca, Carlo J; Kline, Joshua C

    2016-10-01

    Throughout the literature, different observations of motor unit firing behavior during muscle fatigue have been reported and explained with varieties of conjectures. The disagreement amongst previous studies has resulted, in part, from the limited number of available motor units and from the misleading practice of grouping motor unit data across different subjects, contractions, and force levels. To establish a more clear understanding of motor unit control during fatigue, we investigated the firing behavior of motor units from the vastus lateralis muscle of individual subjects during a fatigue protocol of repeated voluntary constant force isometric contractions. Surface electromyographic decomposition technology provided the firings of 1,890 motor unit firing trains. These data revealed that to sustain the contraction force as the muscle fatigued, the following occurred: 1) motor unit firing rates increased; 2) new motor units were recruited; and 3) motor unit recruitment thresholds decreased. Although the degree of these adaptations was subject specific, the behavior was consistent in all subjects. When we compared our empirical observations with those obtained from simulation, we found that the fatigue-induced changes in motor unit firing behavior can be explained by increasing excitation to the motoneuron pool that compensates for the fatigue-induced decrease in muscle force twitch reported in empirical studies. Yet, the fundamental motor unit control scheme remains invariant throughout the development of fatigue. These findings indicate that the central nervous system regulates motor unit firing behavior by adjusting the operating point of the excitation to the motoneuron pool to sustain the contraction force as the muscle fatigues. Copyright © 2016 the American Physiological Society.

  9. 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.

  10. 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.

  11. 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.

  12. Biomolecular logic systems: applications to biosensors and bioactuators

    Science.gov (United States)

    Katz, Evgeny

    2014-05-01

    The paper presents an overview of recent advances in biosensors and bioactuators based on the biocomputing concept. Novel biosensors digitally process multiple biochemical signals through Boolean logic networks of coupled biomolecular reactions and produce output in the form of YES/NO response. Compared to traditional single-analyte sensing devices, biocomputing approach enables a high-fidelity multi-analyte biosensing, particularly beneficial for biomedical applications. Multi-signal digital biosensors thus promise advances in rapid diagnosis and treatment of diseases by processing complex patterns of physiological biomarkers. Specifically, they can provide timely detection and alert to medical emergencies, along with an immediate therapeutic intervention. Application of the biocomputing concept has been successfully demonstrated for systems performing logic analysis of biomarkers corresponding to different injuries, particularly exemplified for liver injury. Wide-ranging applications of multi-analyte digital biosensors in medicine, environmental monitoring and homeland security are anticipated. "Smart" bioactuators, for example for signal-triggered drug release, were designed by interfacing switchable electrodes and biocomputing systems. Integration of novel biosensing and bioactuating systems with the biomolecular information processing systems keeps promise for further scientific advances and numerous practical applications.

  13. Role of biomolecular logic systems in biosensors and bioactuators

    Science.gov (United States)

    Mailloux, Shay; Katz, Evgeny

    2014-09-01

    An overview of recent advances in biosensors and bioactuators based on biocomputing systems is presented. Biosensors digitally process multiple biochemical signals through Boolean logic networks of coupled biomolecular reactions and produce an output in the form of a YES/NO response. Compared to traditional single-analyte sensing devices, the biocomputing approach enables high-fidelity multianalyte biosensing, which is particularly beneficial for biomedical applications. Multisignal digital biosensors thus promise advances in rapid diagnosis and treatment of diseases by processing complex patterns of physiological biomarkers. Specifically, they can provide timely detection and alert medical personnel of medical emergencies together with immediate therapeutic intervention. Application of the biocomputing concept has been successfully demonstrated for systems performing logic analysis of biomarkers corresponding to different injuries, particularly as exemplified for liver injury. Wide-ranging applications of multianalyte digital biosensors in medicine, environmental monitoring, and homeland security are anticipated. "Smart" bioactuators, for signal-triggered drug release, for example, were designed by interfacing switchable electrodes with biocomputing systems. Integration of biosensing and bioactuating systems with biomolecular information processing systems advances the potential for further scientific innovations and various practical applications.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Interaction of cement model systems with superplasticizers investigated by atomic force microscopy, zeta potential, and adsorption measurements.

    Science.gov (United States)

    Ferrari, Lucia; Kaufmann, Josef; Winnefeld, Frank; Plank, Johann

    2010-07-01

    Polyelectrolyte-based dispersants are commonly used in a wide range of industrial applications to provide specific workability to colloidal suspensions. Their working mechanism is based on adsorption onto the surfaces of the suspended particles. The adsorbed polymer layer can exercise an electrostatic and/or a steric effect which is responsible for achieving dispersion. This study is focused on the dispersion forces induced by polycarboxylate ether-based superplasticizers (PCEs) commonly used in concrete. They are investigated by atomic force microscopy (AFM) applying standard silicon nitride tips exposed to solutions with different ionic compositions in a wet cell. Adsorption isotherms and zeta potential analysis were performed to characterize polymer displacement in the AFM system on nonreactive model substrates (quartz, mica, calcite, and magnesium oxide) in order to avoid the complexity of cement hydration products. The results show that PCE is strongly adsorbed by positively charged materials. This fact reveals that, being silicon nitride naturally positively charged, in most cases the superplasticizer adsorbs preferably on the silicon nitride tip than on the AFM substrate. However, the force-distance curves displayed repulsive interactions between tip and substrates even when polymer was poorly adsorbed on both. These observations allow us to conclude that the dispersion due to PCE strongly depends on the particle charge. It differs between colloids adsorbing and not adsorbing PCE, and leads to different forces acting between the particles. Copyright 2010 Elsevier Inc. All rights reserved.

  19. 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.

  20. Prosthetic finger phalanges with lifelike skin compliance for low-force social touching interactions

    Directory of Open Access Journals (Sweden)

    Ge Shuzhi

    2011-03-01

    Full Text Available Abstract Background Prosthetic arms and hands that can be controlled by the user's electromyography (EMG signals are emerging. Eventually, these advanced prosthetic devices will be expected to touch and be touched by other people. As realistic as they may look, the currently available prosthetic hands have physical properties that are still far from the characteristics of human skins because they are much stiffer. In this paper, different configurations of synthetic finger phalanges have been investigated for their skin compliance behaviour and have been compared with the phalanges of the human fingers and a phalanx from a commercially available prosthetic hand. Methods Handshake tests were performed to identify which areas on the human hand experience high contact forces. After these areas were determined, experiments were done on selected areas using an indenting probe to obtain the force-displacement curves. Finite element simulations were used to compare the force-displacement results of the synthetic finger phalanx designs with that of the experimental results from the human and prosthetic finger phalanges. The simulation models were used to investigate the effects of (a varying the internal topology of the finger phalanx and (b varying different materials for the internal and external layers. Results and Conclusions During handshake, the high magnitudes of contact forces were observed at the areas where the full grasping enclosure of the other person's hand can be achieved. From these areas, the middle phalanges of the (a little, (b ring, and (c middle fingers were selected. The indentation experiments on these areas showed that a 2 N force corresponds to skin tissue displacements of more than 2 mm. The results from the simulation model show that introducing an open pocket with 2 mm height on the internal structure of synthetic finger phalanges increased the skin compliance of the silicone material to 235% and the polyurethane material to

  1. Interaction of an anticancer peptide fragment of azurin with p53 and its isolated domains studied by atomic force spectroscopy.

    Science.gov (United States)

    Bizzarri, Anna Rita; Santini, Simona; Coppari, Emilia; Bucciantini, Monica; Di Agostino, Silvia; Yamada, Tohru; Beattie, Craig W; Cannistraro, Salvatore

    2011-01-01

    p28 is a 28-amino acid peptide fragment of the cupredoxin azurin derived from Pseudomonas aeruginosa that preferentially penetrates cancerous cells and arrests their proliferation in vitro and in vivo. Its antitumor activity reportedly arises from post-translational stabilization of the tumor suppressor p53 normally downregulated by the binding of several ubiquitin ligases. This would require p28 to specifically bind to p53 to inhibit specific ligases from initiating proteosome-mediated degradation. In this study, atomic force spectroscopy, a nanotechnological approach, was used to investigate the interaction of p28 with full-length p53 and its isolated domains at the single molecule level. Analysis of the unbinding forces and the dissociation rate constant suggest that p28 forms a stable complex with the DNA-binding domain of p53, inhibiting the binding of ubiquitin ligases other than Mdm2 to reduce proteasomal degradation of p53.

  2. Three-dimensional Force and Kinematic Interactions in V1 Skating at High Speeds.

    Science.gov (United States)

    Stöggl, Thomas; Holmberg, Hans-Christer

    2015-06-01

    To describe the detailed kinetics and kinematics associated with use of the V1 skating technique at high skiing speeds and to identify factors that predict performance. Fifteen elite male cross-country skiers performed an incremental roller-skiing speed test (Vpeak) on a treadmill using the V1 skating technique. Pole and plantar forces and whole-body kinematics were monitored at four submaximal speeds. The propulsive force of the "strong side" pole was greater than that of the "weak side" (P skating at high speeds. The faster skiers exhibit more symmetric leg motion on the "strong" and "weak" sides, as well as more synchronized poling. With respect to methods, the pressure insoles and three-dimensional kinematics in combination with the leg push-off model described here can easily be applied to all skating techniques, aiding in the evaluation of skiing techniques and comparison of effectiveness.

  3. What is the impact of natural variability and aerosol-cloud interaction on the effective radiative forcing of anthropogenic aerosol?

    Science.gov (United States)

    Fiedler, S.; Stevens, B.; Mauritsen, T.

    2017-12-01

    State-of-the-art climate models have persistently shown a spread in estimates of the effective radiative forcing (ERF) associated with anthropogenic aerosol. Different reasons for the spread are known, but their relative importance is poorly understood. In this presentation we investigate the role of natural atmospheric variability, global patterns of aerosol radiative effects, and magnitudes of aerosol-cloud interaction in controlling the ERF of anthropogenic aerosol (Fiedler et al., 2017). We use the Earth system model MPI-ESM1.2 for conducting ensembles of atmosphere-only simulations and calculate the shortwave ERF of anthropogenic aerosol at the top of the atmosphere. The radiative effects are induced with the new parameterisation MACv2-SP (Stevens et al., 2017) that prescribes observationally constrained anthropogenic aerosol optical properties and an associated Twomey effect. Firstly, we compare the ERF of global patterns of anthropogenic aerosol from the mid-1970s and today. Our results suggest that such a substantial pattern difference has a negligible impact on the global mean ERF, when the natural variability of the atmosphere is considered. The clouds herein efficiently mask the clear-sky contributions to the forcing and reduce the detectability of significant anthropogenic aerosol radiative effects in all-sky conditions. Secondly, we strengthen the forcing magnitude through increasing the effect of aerosol-cloud interaction by prescribing an enhanced Twomey effect. In that case, the different spatial pattern of aerosol radiative effects from the mid-1970s and today causes a moderate change (15%) in the ERF of anthropogenic aerosol in our model. This finding lets us speculate that models with strong aerosol-cloud interactions would show a stronger ERF change with anthropogenic aerosol patterns. Testing whether the anthropogenic aerosol radiative forcing is model-dependent under prescribed aerosol conditions is currently ongoing work using MACv2-SP in

  4. Forcings and feedbacks on convection in the 2010 Pakistan flood: Modeling extreme precipitation with interactive large-scale ascent

    Science.gov (United States)

    Nie, Ji; Shaevitz, Daniel A.; Sobel, Adam H.

    2016-09-01

    Extratropical extreme precipitation events are usually associated with large-scale flow disturbances, strong ascent, and large latent heat release. The causal relationships between these factors are often not obvious, however, the roles of different physical processes in producing the extreme precipitation event can be difficult to disentangle. Here we examine the large-scale forcings and convective heating feedback in the precipitation events, which caused the 2010 Pakistan flood within the Column Quasi-Geostrophic framework. A cloud-revolving model (CRM) is forced with large-scale forcings (other than large-scale vertical motion) computed from the quasi-geostrophic omega equation using input data from a reanalysis data set, and the large-scale vertical motion is diagnosed interactively with the simulated convection. Numerical results show that the positive feedback of convective heating to large-scale dynamics is essential in amplifying the precipitation intensity to the observed values. Orographic lifting is the most important dynamic forcing in both events, while differential potential vorticity advection also contributes to the triggering of the first event. Horizontal moisture advection modulates the extreme events mainly by setting the environmental humidity, which modulates the amplitude of the convection's response to the dynamic forcings. When the CRM is replaced by either a single-column model (SCM) with parameterized convection or a dry model with a reduced effective static stability, the model results show substantial discrepancies compared with reanalysis data. The reasons for these discrepancies are examined, and the implications for global models and theoretical models are discussed.

  5. Novel Structures for the Excess Electron State of the Water Hexamer and the Interaction Forces Governing the Structures

    International Nuclear Information System (INIS)

    Lee, S.; Kim, J.; Lee, S.J.; Kim, K.S.

    1997-01-01

    The geometrical and electronic structures of partially hydrated electron systems, in particular, the water hexamer, which have been controversial for decades, have been clarified by an exhaustive search for possible low-lying energy structures. Several competing interaction forces governing the conformation have been examined for the first time. The low-lying energy structures are hybrid (or partially internal and partially surface) excess electron states. Our prediction is evidenced from excellent agreements with available experimental data. The vertical electron-detachment energies are mainly determined by the number of dangling H atoms (H d ) . copyright 1997 The American Physical Society

  6. Intermuscular interaction via myofascial force transmission: Effects of tibialis anterior and extensor digitorum longus length on force transmission from rat extensor digitorum longus muscle

    NARCIS (Netherlands)

    Maas, Huub; Baan, Guus C.; Huijing, P.A.J.B.M.

    2001-01-01

    Force transmission in rat anterior crural compartment, containing tibialis anterior (TA), extensor hallucis longus (EHL) and extensor digitorum longus (EDL) muscles, was investigated. These muscles together with the muscles of the peroneal compartment were excited maximally. Force was measured at

  7. Atomic forces between noble gas atoms, alkali ions, and halogen ions for surface interactions

    Science.gov (United States)

    Wilson, J. W.; Outlaw, R. A.; Heinbockel, J. H.

    1988-01-01

    The components of the physical forces between noble gas atoms, alkali ions, and halogen ions are analyzed and a data base developed from analysis of the two-body potential data, the alkali-halide molecular data, and the noble gas crystal and salt crystal data. A satisfactory global fit to this molecular and crystal data is then reproduced by the model to within several percent. Surface potentials are evaluated for noble gas atoms on noble gas surfaces and salt crystal surfaces with surface tension neglected. Within this context, the noble gas surface potentials on noble gas and salt crystals are considered to be accurate to within several percent.

  8. The triel bond: a potential force for tuning anion-π interactions

    Science.gov (United States)

    Esrafili, Mehdi D.; Mousavian, Parisasadat

    2018-02-01

    Using ab-initio calculations, the mutual influence between anion-π and B···N or B···C triel bond interactions is investigated in some model complexes. The properties of these complexes are studied by molecular electrostatic potential, noncovalent interaction index, quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses. According to the results, the formation of B···N or B···C triel bond interactions in the multi-component systems makes a significant shortening of anion-π distance. Such remarkable variation in the anion-π distances has not been reported previously. The strengthening of the anion-π bonding in the multi-component systems depend significantly on the nature of the anion, and it becomes larger in the order Br- > Cl- > F-. The parameters derived from the QTAIM and NBO methodologies are used to study the mechanism of the cooperativity between the anion-π and triel bond interactions in the multi-component complexes.

  9. An atomic force microscopy study of the interactions between indolicidin and supported planar bilayers

    DEFF Research Database (Denmark)

    Askou, Hans Jakob; Jakobsen, Rasmus Neergaard; Fojan, Peter

    2008-01-01

    . The present study indicates that the mode of action for indolicidin can be best described by a stepwise interaction of the peptide with the membrane. Formation of pores however can not be supported on the basis of our experiments. (Cited By) View on PubMed PMID: 19049026 Udgivelsesdato: SEP...

  10. Experimental study of the molten glass/water thermal interaction under free and forced conditions

    International Nuclear Information System (INIS)

    Arakeri, V.H.; Catton, I.; Kastenberg, W.E.

    1978-01-01

    Molten glass interacts explosively with water under certain contact mode conditions. The contact mode found explosive is as follows: Molten glass enters the water bath in the film boiling regime (as predicted by Dhir's correlation), and soon after entry the vapor film is perturbed sufficiently by an external pressure pulse. The ensuing reaction proceeds basically along the same lines as energetic tin/water interactions observed by several investigators. In the absence of this pressure pulse, the event is nonenergetic. The present findings are for a combination in which the hot material has a very low thermal diffusivity and the calculated interface temperature is significantly (approximately 180 K) below its melting temperature. This is similar to the characteristics of the UO 2 /sodium or UO 2 /water combinations. The observed explosive glass/water interactions show growth times on the order of a few milliseconds. The particulate size distribution from the present tests was coarser than the particulate size distribution from some in-pile and out-of-pile UO 2 /sodium interaction tests

  11. Assessing the relative importance of parameter and forcing uncertainty and their interactions in conceptual hydrological model simulations

    Science.gov (United States)

    Mockler, E. M.; Chun, K. P.; Sapriza-Azuri, G.; Bruen, M.; Wheater, H. S.

    2016-11-01

    Predictions of river flow dynamics provide vital information for many aspects of water management including water resource planning, climate adaptation, and flood and drought assessments. Many of the subjective choices that modellers make including model and criteria selection can have a significant impact on the magnitude and distribution of the output uncertainty. Hydrological modellers are tasked with understanding and minimising the uncertainty surrounding streamflow predictions before communicating the overall uncertainty to decision makers. Parameter uncertainty in conceptual rainfall-runoff models has been widely investigated, and model structural uncertainty and forcing data have been receiving increasing attention. This study aimed to assess uncertainties in streamflow predictions due to forcing data and the identification of behavioural parameter sets in 31 Irish catchments. By combining stochastic rainfall ensembles and multiple parameter sets for three conceptual rainfall-runoff models, an analysis of variance model was used to decompose the total uncertainty in streamflow simulations into contributions from (i) forcing data, (ii) identification of model parameters and (iii) interactions between the two. The analysis illustrates that, for our subjective choices, hydrological model selection had a greater contribution to overall uncertainty, while performance criteria selection influenced the relative intra-annual uncertainties in streamflow predictions. Uncertainties in streamflow predictions due to the method of determining parameters were relatively lower for wetter catchments, and more evenly distributed throughout the year when the Nash-Sutcliffe Efficiency of logarithmic values of flow (lnNSE) was the evaluation criterion.

  12. Forces and torques on rigid inclusions in an elastic environment: Resulting matrix-mediated interactions, displacements, and rotations

    Science.gov (United States)

    Puljiz, Mate; Menzel, Andreas M.

    2017-05-01

    Embedding rigid inclusions into elastic matrix materials is a procedure of high practical relevance, for instance, for the fabrication of elastic composite materials. We theoretically analyze the following situation. Rigid spherical inclusions are enclosed by a homogeneous elastic medium under stick boundary conditions. Forces and torques are directly imposed from outside onto the inclusions or are externally induced between them. The inclusions respond to these forces and torques by translations and rotations against the surrounding elastic matrix. This leads to elastic matrix deformations, and in turn results in mutual long-ranged matrix-mediated interactions between the inclusions. Adapting a well-known approach from low-Reynolds-number hydrodynamics, we explicitly calculate the displacements and rotations of the inclusions from the externally imposed or induced forces and torques. Analytical expressions are presented as a function of the inclusion configuration in terms of displaceability and rotateability matrices. The role of the elastic environment is implicitly included in these relations. That is, the resulting expressions allow a calculation of the induced displacements and rotations directly from the inclusion configuration, without having to explicitly determine the deformations of the elastic environment. In contrast to the hydrodynamic case, compressibility of the surrounding medium is readily taken into account. We present the complete derivation based on the underlying equations of linear elasticity theory. In the future, the method will, for example, be helpful to characterize the behavior of externally tunable elastic composite materials, to accelerate numerical approaches, as well as to improve the quantitative interpretation of microrheological results.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Effects of interactive technology, teacher scaffolding and feedback on university students' conceptual development in motion and force concepts

    Science.gov (United States)

    Stecklein, Jason Jeffrey

    The utilization of interactive technologies will affect learning in science classrooms of the future. And although these technologies have improved in form and function, their effective employment in university science classrooms has lagged behind the rapid development of new constructivist pedagogies and means of instruction. This dissertation examines the enlistment of instructional technologies, in particular tablet PCs and DyKnow Interactive Software, in a technologically enhanced, university-level, introductory physics course. Results of this qualitative case study of three university students indicate that (1) the use of interactive technology positively affects both student learning within force and motion and self-reported beliefs about physics, (2) ad hoc use of instructional technologies may not sufficient for effective learning in introductory physics, (3) student learners dictate the leveraging of technology in any classroom, and (4) that purposeful teacher structuring of classroom activities with technologies are essential for student construction of knowledge. This includes designing activities to elicit attention and make knowledge visible for low-level content, while augmenting student interactions and modelling procedural steps for higher-level content.

  4. Surface capillary currents: Rediscovery of fluid-structure interaction by forced evolving boundary theory

    Science.gov (United States)

    Wang, Chunbai; Mitra, Ambar K.

    2016-01-01

    Any boundary surface evolving in viscous fluid is driven with surface capillary currents. By step function defined for the fluid-structure interface, surface currents are found near a flat wall in a logarithmic form. The general flat-plate boundary layer is demonstrated through the interface kinematics. The dynamics analysis elucidates the relationship of the surface currents with the adhering region as well as the no-slip boundary condition. The wall skin friction coefficient, displacement thickness, and the logarithmic velocity-defect law of the smooth flat-plate boundary-layer flow are derived with the advent of the forced evolving boundary method. This fundamental theory has wide applications in applied science and engineering.

  5. Nonequilibrium thermodynamics of interacting tunneling transport: variational grand potential, density functional formulation and nature of steady-state forces

    International Nuclear Information System (INIS)

    Hyldgaard, P

    2012-01-01

    The standard formulation of tunneling transport rests on an open-boundary modeling. There, conserving approximations to nonequilibrium Green function or quantum statistical mechanics provide consistent but computational costly approaches; alternatively, the use of density-dependent ballistic-transport calculations (e.g., Lang 1995 Phys. Rev. B 52 5335), here denoted ‘DBT’, provides computationally efficient (approximate) atomistic characterizations of the electron behavior but has until now lacked a formal justification. This paper presents an exact, variational nonequilibrium thermodynamic theory for fully interacting tunneling and provides a rigorous foundation for frozen-nuclei DBT calculations as a lowest-order approximation to an exact nonequilibrium thermodynamic density functional evaluation. The theory starts from the complete electron nonequilibrium quantum statistical mechanics and I identify the operator for the nonequilibrium Gibbs free energy which, generally, must be treated as an implicit solution of the fully interacting many-body dynamics. I demonstrate a minimal property of a functional for the nonequilibrium thermodynamic grand potential which thus uniquely identifies the solution as the exact nonequilibrium density matrix. I also show that the uniqueness-of-density proof from a closely related Lippmann-Schwinger collision density functional theory (Hyldgaard 2008 Phys. Rev. B 78 165109) makes it possible to express the variational nonequilibrium thermodynamic description as a single-particle formulation based on universal electron-density functionals; the full nonequilibrium single-particle formulation improves the DBT method, for example, by a more refined account of Gibbs free energy effects. I illustrate a formal evaluation of the zero-temperature thermodynamic grand potential value which I find is closely related to the variation in the scattering phase shifts and hence to Friedel density oscillations. This paper also discusses the

  6. The diurnal interaction between convection and peninsular-scale forcing over South Florida

    Science.gov (United States)

    Cooper, H. J.; Simpson, J.; Garstang, M.

    1982-01-01

    One of the outstanding problems in modern meterology is that of describing in detail the manner in which larger scales of motion interact with, influence and are influenced by successively smaller scales of motion. The present investigation is concerned with a study of the diurnal evolution of convection, the interaction between the peninsular-scale convergence and convection, and the role of the feedback produced by the cloud-scale downdrafts in the maintenance of the convection. Attention is given to the analysis, the diurnal cycle of the network area-averaged divergence, convective-scale divergence, convective mass transports, and the peninsular scale divergence. The links established in the investigation between the large scale (peninsular), the mesoscale (network), and the convective scale (cloud) are found to be of fundamental importance to the understanding of the initiation, maintenance, and decay of deep precipitating convection and to its theoretical parameterization.

  7. Components interaction in timber framed masonry structures subjected to lateral forces

    Directory of Open Access Journals (Sweden)

    Andreea DUTU

    2012-07-01

    Full Text Available Structures with timber framed masonry represent a special typology that is frequently found in Europe and other countries of the world. They are traditional buildings, non-engineered, which showed an unexpected redundancy during earthquakes where reinforced concrete buildings (improperly constructed collapsed. In the paper, aspects regarding the interaction between timber elements and masonry are mainly addressed, that were observed both in experimental studies, but also in the in situ seismic behavior of this type of structure during important earthquakes.

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

    Science.gov (United States)

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

    2017-10-01

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

  9. 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)

  10. A model of hydraulic interactions in liver parenchyma as forces behind the intrahepatic bile flow.

    Science.gov (United States)

    Kurbel, S; Kurbel, B; Dmitrovic, B; Wagner, J

    2001-05-01

    The small diameters of bile canaliculi and interlobular bile ducts make it hard to attribute the bile flow solely to the process of secretion. In the model liver within its capsule is considered a limited space in which volume expansions of one part are possible only through the shrinking of other parts. The liver capsule allows only very slow volume changes. The rate of blood flow through the sinusoides is governed by the Poisseuill-Hagen law. The model is based on a concept of circulatory liver units. A unit would contain a group of acini sharing the same conditions of arterial flow. We can imagine them as an acinar group behind the last pressure reducer on one arterial branch. Acini from neighboring units compose liver lobules and drain through the same central venule. One lobule can contain acini from several neighboring circulatory units. The perfusion cycle in one unit begins with a transient tide in the arterial flow, governed by local mediators. Corresponding acini expand, grabbing the space by compressing their neighbors in the same lobules. Vascular resistance is reduced in dilated and increased in compressed acini. Portal blood flows through the dilated acini, bypassing the compressed neighbors. The cycle ends when the portal tide slowly diminishes and acinar volume is back on the interphase value until the new perfusion cycle is started in another circulatory unit. Each cycle probably takes minutes to complete. Increased pressures both in dilated and in compressed acini force the bile to move from acinar canalicules. Both up and down changes in acinar volume might force the acinar biliary flow. In cases of arterial vasoconstriction, increased activity of vasoactive substances would keep most of the circulatory units in the interphase and increased liver resistance can be expected. Liver fibrosis makes all acini to be of fixed volume and result in increased resistance. Because of that, low pressure portal flow would be more compromised, as reported. In

  11. Recursive evaluation of interaction forces of unbounded soil in time domain

    International Nuclear Information System (INIS)

    Motosaka, M.

    1987-01-01

    Recursive formulations have hardly been used in the analysis of soil-structure interaction. A notable exception is described in Verbic 1973, which corresponds to the impulse-invariant way discussed in Section 2. Section 3 describes another possibility to derive a recursive relation based on a segment approach using z-transforms. An illustrative example is examined in Section 4, and in Section 5 the number of operations is addressed. This compact paper is based on Wolf and Motosaka 1988. (orig./HP)

  12. Correlated fermionic densities for many harmonically trapped particles interacting with repulsive forces

    International Nuclear Information System (INIS)

    Glasser, M.L.; March, N.H.; Nieto, L.M.

    2010-01-01

    This study is motivated by the very recent work on correlation energy as approximated by the Thomas-Fermi (TF) semiclassical limit [B.R. Landry, et al., Phys. Rev. Lett. 103 (2009) 066401]. In contrast, and motivated by the Hohenberg-Kohn theorem, our work is focussed primarily on the correlated TF ground-state density. We invoke directly the Holas et al. result that for two-fermion systems with harmonic trapping, the fermion-fermion interaction u simply adds to the trapping potential. We conclude this report with some results on correlation kinetic energy for two-fermion systems.

  13. Quantitative assessment of intermolecular interactions by atomic force microscopy imaging using copper oxide tips

    Science.gov (United States)

    Mönig, Harry; Amirjalayer, Saeed; Timmer, Alexander; Hu, Zhixin; Liu, Lacheng; Díaz Arado, Oscar; Cnudde, Marvin; Strassert, Cristian Alejandro; Ji, Wei; Rohlfing, Michael; Fuchs, Harald

    2018-05-01

    Atomic force microscopy is an impressive tool with which to directly resolve the bonding structure of organic compounds1-5. The methodology usually involves chemical passivation of the probe-tip termination by attaching single molecules or atoms such as CO or Xe (refs 1,6-9). However, these probe particles are only weakly connected to the metallic apex, which results in considerable dynamic deflection. This probe particle deflection leads to pronounced image distortions, systematic overestimation of bond lengths, and in some cases even spurious bond-like contrast features, thus inhibiting reliable data interpretation8-12. Recently, an alternative approach to tip passivation has been used in which slightly indenting a tip into oxidized copper substrates and subsequent contrast analysis allows for the verification of an oxygen-terminated Cu tip13-15. Here we show that, due to the covalently bound configuration of the terminal oxygen atom, this copper oxide tip (CuOx tip) has a high structural stability, allowing not only a quantitative determination of individual bond lengths and access to bond order effects, but also reliable intermolecular bond characterization. In particular, by removing the previous limitations of flexible probe particles, we are able to provide conclusive experimental evidence for an unusual intermolecular N-Au-N three-centre bond. Furthermore, we demonstrate that CuOx tips allow the characterization of the strength and configuration of individual hydrogen bonds within a molecular assembly.

  14. Fixed-Charge Atomistic Force Fields for Molecular Dynamics Simulations in the Condensed Phase: An Overview.

    Science.gov (United States)

    Riniker, Sereina

    2018-03-26

    In molecular dynamics or Monte Carlo simulations, the interactions between the particles (atoms) in the system are described by a so-called force field. The empirical functional form of classical fixed-charge force fields dates back to 1969 and remains essentially unchanged. In a fixed-charge force field, the polarization is not modeled explicitly, i.e. the effective partial charges do not change depending on conformation and environment. This simplification allows, however, a dramatic reduction in computational cost compared to polarizable force fields and in particular quantum-chemical modeling. The past decades have shown that simulations employing carefully parametrized fixed-charge force fields can provide useful insights into biological and chemical questions. This overview focuses on the four major force-field families, i.e. AMBER, CHARMM, GROMOS, and OPLS, which are based on the same classical functional form and are continuously improved to the present day. The overview is aimed at readers entering the field of (bio)molecular simulations. More experienced users may find the comparison and historical development of the force-field families interesting.

  15. The Ambiguity of Militarization : The complex interaction between the Congolese armed forces and civilians in the Kivu provinces, eastern DR Congo

    NARCIS (Netherlands)

    Verweijen, J.E.C.

    2015-01-01

    Drawing on extensive ethnographic field research, this dissertation explores the interaction between the Congolese armed forces (FARDC) and civilians in the eastern DR Congo’s conflict-ridden Kivu provinces. It uncovers the multidimensionality, reciprocity and complexities of this interaction, which

  16. 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

  17. Atomic Force Microscopy Probing of Receptor–Nanoparticle Interactions for Riboflavin Receptor Targeted Gold–Dendrimer Nanocomposites

    Science.gov (United States)

    2015-01-01

    Riboflavin receptors are overexpressed in malignant cells from certain human breast and prostate cancers, and they constitute a group of potential surface markers important for cancer targeted delivery of therapeutic agents and imaging molecules. Here we report on the fabrication and atomic force microscopy (AFM) characterization of a core–shell nanocomposite consisting of a gold nanoparticle (AuNP) coated with riboflavin receptor-targeting poly(amido amine) dendrimer. We designed this nanocomposite for potential applications such as a cancer targeted imaging material based on its surface plasmon resonance properties conferred by AuNP. We employed AFM as a technique for probing the binding interaction between the nanocomposite and riboflavin binding protein (RfBP) in solution. AFM enabled precise measurement of the AuNP height distribution before (13.5 nm) and after chemisorption of riboflavin-conjugated dendrimer (AuNP–dendrimer; 20.5 nm). Binding of RfBP to the AuNP–dendrimer caused a height increase to 26.7 nm, which decreased to 22.8 nm when coincubated with riboflavin as a competitive ligand, supporting interaction of AuNP–dendrimer and its target protein. In summary, physical determination of size distribution by AFM imaging can serve as a quantitative approach to monitor and characterize the nanoscale interaction between a dendrimer-covered AuNP and target protein molecules in vitro. PMID:24571134

  18. Genuine two-fluid computations of laser-plasma interaction for generation of nonlinear force driven plasma blocks

    International Nuclear Information System (INIS)

    Nafari, F.; Yazdani, E.; Malekynia, B.; Ghoranneviss, M.

    2010-01-01

    Complete text of publication follows. Anomalous interaction of picosecond laser pulses of terawatt to petawatt power is due to suppression of relativistic self-focusing if prepulses are cut-off by a contrast ratio higher than 10 8 . Resulting non-linear ponderomotive forces induced at the skin-layer interaction of a short laser-pulse with a proper preplasma layer produced by the laser prepulse in front of a solid target accelerate two thin (a few μm) quasi-neutral plasma blocks, propagating in forward and backward directions, backward moving against the laser light (ablation) and forward moving into the target. This compressed block produces an ion current density of above 10 11 A/cm 2 . This may support the requirement to produce a fast ignition deuterium tritium fusion at densities not much higher than the solid state by a single shot pw-ps laser pulse. With studying skin-layer subrelativistic interaction of a short (≤ 1 ps) laser pulse with an initial Rayleigh density profile in genuine two-fluid hydrodynamic model, time and spatial distributions of ion block temperature are presented.

  19. Experimental and numerical modelling of surface water-groundwater flow and pollution interactions under tidal forcing

    Science.gov (United States)

    Spanoudaki, Katerina; Bockelmann-Evans, Bettina; Schaefer, Florian; Kampanis, Nikolaos; Nanou-Giannarou, Aikaterini; Stamou, Anastasios; Falconer, Roger

    2015-04-01

    Surface water and groundwater are integral components of the hydrologic continuum and the interaction between them affects both their quantity and quality. However, surface water and groundwater are often considered as two separate systems and are analysed independently. This separation is partly due to the different time scales, which apply in surface water and groundwater flows and partly due to the difficulties in measuring and modelling their interactions (Winter et al., 1998). Coastal areas in particular are a difficult hydrologic environment to represent with a mathematical model due to the large number of contributing hydrologic processes. Accurate prediction of interactions between coastal waters, groundwater and neighbouring wetlands, for example, requires the use of integrated surface water-groundwater models. In the past few decades a large number of mathematical models and field methods have been developed in order to quantify the interaction between groundwater and hydraulically connected surface water bodies. Field studies may provide the best data (Hughes, 1995) but are usually expensive and involve too many parameters. In addition, the interpretation of field measurements and linking with modelling tools often proves to be difficult. In contrast, experimental studies are less expensive and provide controlled data. However, experimental studies of surface water-groundwater interaction are less frequently encountered in the literature than filed studies (e.g. Ebrahimi et al., 2007; Kuan et al., 2012; Sparks et al., 2013). To this end, an experimental model has been constructed at the Hyder Hydraulics Laboratory at Cardiff University to enable measurements to be made of groundwater transport through a sand embankment between a tidal water body such as an estuary and a non-tidal water body such as a wetland. The transport behaviour of a conservative tracer was studied for a constant water level on the wetland side of the embankment, while running a

  20. 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...

  1. 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.)

  2. Fluid-Structure Interaction Analysis of Papillary Muscle Forces Using a Comprehensive Mitral Valve Model with 3D Chordal Structure.

    Science.gov (United States)

    Toma, Milan; Jensen, Morten Ø; Einstein, Daniel R; Yoganathan, Ajit P; Cochran, Richard P; Kunzelman, Karyn S

    2016-04-01

    Numerical models of native heart valves are being used to study valve biomechanics to aid design and development of repair procedures and replacement devices. These models have evolved from simple two-dimensional approximations to complex three-dimensional, fully coupled fluid-structure interaction (FSI) systems. Such simulations are useful for predicting the mechanical and hemodynamic loading on implanted valve devices. A current challenge for improving the accuracy of these predictions is choosing and implementing modeling boundary conditions. In order to address this challenge, we are utilizing an advanced in vitro system to validate FSI conditions for the mitral valve system. Explanted ovine mitral valves were mounted in an in vitro setup, and structural data for the mitral valve was acquired with [Formula: see text]CT. Experimental data from the in vitro ovine mitral valve system were used to validate the computational model. As the valve closes, the hemodynamic data, high speed leaflet dynamics, and force vectors from the in vitro system were compared to the results of the FSI simulation computational model. The total force of 2.6 N per papillary muscle is matched by the computational model. In vitro and in vivo force measurements enable validating and adjusting material parameters to improve the accuracy of computational models. The simulations can then be used to answer questions that are otherwise not possible to investigate experimentally. This work is important to maximize the validity of computational models of not just the mitral valve, but any biomechanical aspect using computational simulation in designing medical devices.

  3. SIMULATION OF THE FORCE INTERACTION OF THE SOIL COMPACTING DISK MOVING ALONG A RHEOLOGICAL BEAM THAT HAS DISTRIBUTED MASS

    Directory of Open Access Journals (Sweden)

    Pavlov Georgiy Vasil'evich

    2012-10-01

    Full Text Available The authors describe an original solution to the new problem of a soil compacting disk moving along a rheological beam (Kelvin model in the proposed paper. The motion of the mechanical system that is composed of a disk and a rheological beam is described by a hybrid system of differential equations consisting of an integral-differential equation that stands for the interaction of the beam with a moving disk and Lagrange equations describing the pattern of the disk motion. These equations are considered as equations of nonholonomic links. The problem is solved through the employment of simplifying prerequisites and by determining the operating condition of the disk. Condition of uniform and uniformly variable motions is considered as an opportunity to integrate the equation of beam vibrations regardless of the system of equations describing the disk motion pattern. The solution to the equation in partial derivatives is found through the employment of the Fourier method of separation of variables coupled with the Laplace integral transformation method. The solution to the problem of constrained vibrations was implemented as a series of homogenous problems with zero initial and boundary conditions. The equation describing changes in the time function is reduced to its standard form, and thereafter the solution is found through the employment of asymptotic methods. Disk motion stability is assessed through the employment of the first approximation method. The motion of the disk is stable. As a result of the analysis of patterns of dependencies between beam deformations and the time period, the conclusion of feasibility of a stable pattern of forced vibrations of a rheological beam, supported by a driving force and a variable friction force, caused by the slightly elastic field of the beam material, is made by the authors.

  4. Flame-vortex interaction and mixing behaviors of turbulent non-premixed jet flames under acoustic forcing

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Munki; Choi, Youngil; Oh, Jeongseog; Yoon, Youngbin [School of Mechanical and Aerospace Engineering, Seoul National University, Seoul (Korea)

    2009-12-15

    This study examines the effect of acoustic excitation using forced coaxial air on the flame characteristics of turbulent hydrogen non-premixed flames. A resonance frequency was selected to acoustically excite the coaxial air jet due to its ability to effectively amplify the acoustic amplitude and reduce flame length and NO{sub x} emissions. Acoustic excitation causes the flame length to decrease by 15% and consequently, a 25% reduction in EINO{sub x} is achieved, compared to coaxial air flames without acoustic excitation at the same coaxial air to fuel velocity ratio. Moreover, acoustic excitation induces periodical fluctuation of the coaxial air velocity, thus resulting in slight fluctuation of the fuel velocity. From phase-lock PIV and OH PLIF measurement, the local flow properties at the flame surface were investigated under acoustic forcing. During flame-vortex interaction in the near field region, the entrainment velocity and the flame surface area increased locally near the vortex. This increase in flame surface area and entrainment velocity is believed to be a crucial factor in reducing flame length and NO{sub x} emission in coaxial jet flames with acoustic excitation. Local flame extinction occurred frequently when subjected to an excessive strain rate, indicating that intense mass transfer of fuel and air occurs radially inward at the flame surface. (author)

  5. Interaction and dynamics of ambient water adlayers on graphite probed using AFM voltage nanolithography and electrostatic force microscopy

    International Nuclear Information System (INIS)

    Gowthami, T; Raina, Gargi; Kurra, Narendra

    2014-01-01

    In this work, we report the impact of the interaction and dynamics of increasing ambient water adlayers on etch patterns on a hydrophobic highly oriented pyrolytic graphite (HOPG) surface obtained using atomic force microscopy (AFM) voltage nanolithography in contact mode by applying a positive bias to the sample. The changes in the dimensions of the etch patterns were investigated as a function of the increasing number of water adlayers present on the HOPG, which is varied by changing the time interval since HOPG cleavage. Changes in the width of the etch patterns and the surrounding water droplets were monitored with time, using intermittent-contact-mode AFM. Electrostatic force microscopy (EFM) has been employed to study the charged nature of the etch patterns and the neighboring water film with time. The width of the etch patterns made on freshly cleaved HOPG shows an increase of ∼33% over 48 h, whereas nine-day-old cleaved HOPG shows a 79% increase over the same period. No changes in the dimensions are observed while imaging in a nitrogen atmosphere soon after lithography. In ambient conditions, the EFM phase shift of the patterns shows a large change of ∼84–88% over 30 h. This study demonstrates the effect of the stored electrostatic energy of a polarized ice-like water adlayer, resulting in changes in the dimensions of the etch patterns long after lithography, whereas liquid-like water droplets do not affect the etch patterns. (paper)

  6. A numerical modeling study of the interaction between the tides and the circulation forced by high-latitude plasma convection

    International Nuclear Information System (INIS)

    Mikkelsen, I.S.; Larsen, M.F.

    1991-01-01

    A spectral, time-varying thermospheric general circulation model has been used to study the nonlinear interaction at high latitudes between the tides propagating into the thermosphere from below and the circulation induced by magnetospheric forcing and in situ solar heating. The model is discrete in the vertical with 27 layers spaced by half a scale height. In the horizontal, the fields are expanded in a series of spherical harmonics using a triangular truncation at wave number 31, equivalent to a homogeneous global resolution with a minimum wavelength of 1,270 km. A hypothetical uniform grid point model would require a horizontal spacing of 417 km to describe the same minimum wavelength. In the high-latitude F region the tides affect the dusk vortex of the neutral flow very little, but the dawn vortex is either suppressed or amplified dependent upon the universal time and tidal phase. In the E region neutral flow, both the dusk and dawn vortices are shifted in local time by the tides, again as a function of universal time and tidal phase. At dusk a nonlinear amplification of the sunward winds occurs for certain combination of parameters, and at dawn the winds may be completely suppressed. Below 120 km altitude the magnetospheric forcing creates a single cyclonic vortex which is also sensitive to the high-latitude tidal structure

  7. Relativistic effects in ultra-high-intensity laser-plasma interaction: electron parametric instabilities and ponderomotive force

    International Nuclear Information System (INIS)

    Quesnel, Brice

    1998-01-01

    This research thesis reports a theoretical and numeric study of the behaviour of two non linear phenomena of the laser-plasma interaction physics in a relativistic regime: the electronic parametric instabilities, and the ponderomotive force. In a first part, the author establishes the three-dimensional scattering relationship of electron parametric instabilities for a circularly polarised wave propagating in a homogeneous and cold plasma, without limitations of wave intensity, nor of plasma density. Results are verified by comparison with those of two-dimensional numerical simulations. The Weibel instability is also briefly studied in relativistic regime. In the second part, the author establishes an expression of the ponderomotive force exerted by an ultra-intense laser pulse in the vacuum about the focus point. A numerical code of integration of equations of motion of an electron in the laser field is used for the different expressions corresponding different approximation degrees. Results are used to interpret a recent experiment, and to critic other theoretical works [fr

  8. Relative importance of driving force and electrostatic interactions in the reduction of multihaem cytochromes by small molecules.

    Science.gov (United States)

    Quintas, Pedro O; Cepeda, Andreia P; Borges, Nuno; Catarino, Teresa; Turner, David L

    2013-06-01

    Multihaem cytochromes are essential to the energetics of organisms capable of bioremediation and energy production. The haems in several of these cytochromes have been discriminated thermodynamically and their individual rates of reduction by small electron donors were characterized. The kinetic characterization of individual haems used the Marcus theory of electron transfer and assumed that the rates of reduction of each haem by sodium dithionite depend only on the driving force, while electrostatic interactions were neglected. To determine the relative importance of these factors in controlling the rates, we studied the effect of ionic strength on the redox potential and the rate of reduction by dithionite of native Methylophilus methylotrophus cytochrome c″ and three mutants at different pH values. We found that the main factor determining the rate is the driving force and that Marcus theory describes this satisfactorily. This validates the method of the simultaneous fitting of kinetic and thermodynamic data in multihaem cytochromes and opens the way for further investigation into the mechanisms of these proteins. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. AFM force spectroscopy reveals how subtle structural differences affect the interaction strength between Candida albicans and DC-SIGN.

    Science.gov (United States)

    te Riet, Joost; Reinieren-Beeren, Inge; Figdor, Carl G; Cambi, Alessandra

    2015-11-01

    The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, such as the C-type lectin dendritic cell-specific intracellular cell adhesion molecule-3 (ICAM-3)-grabbing non-integrin (DC-SIGN), because a detailed characterization at the structural level is lacking. DC-SIGN recognizes specific Candida-associated molecular patterns, that is, mannan structures present in the cell wall of Candida. The molecular recognition mechanism is however poorly understood. We postulated that small differences in mannan-branching may result in considerable differences in the binding affinity. Here, we exploit atomic force microscope-based dynamic force spectroscopy with single Candida cells to gain better insight in the carbohydrate recognition capacity of DC-SIGN. We demonstrate that slight differences in the N-mannan structure of Candida, that is, the absence or presence of a phosphomannan side chain, results in differences in the recognition by DC-SIGN as follows: (i) it contributes to the compliance of the outer cell wall of Candida, and (ii) its presence results in a higher binding energy of 1.6 kB T. The single-bond affinity of tetrameric DC-SIGN for wild-type C. albicans is ~10.7 kB T and a dissociation constant kD of 23 μM, which is relatively strong compared with other carbohydrate-protein interactions described in the literature. In conclusion, this study shows that DC-SIGN specifically recognizes mannan patterns on C. albicans with high affinity. Knowledge on the binding pocket of DC-SIGN and its pathogenic ligands will lead to a better understanding of how fungal-associated carbohydrate structures are recognized by receptors of the immune system and can ultimately contribute to the development of new anti-fungal drugs. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Plasma parameters and electromagnetic forces induced by the magneto hydro dynamic interaction in a hypersonic argon flow experiment

    International Nuclear Information System (INIS)

    Cristofolini, Andrea; Neretti, Gabriele; Borghi, Carlo A.

    2012-01-01

    This work proposes an experimental analysis on the magneto hydro dynamic (MHD) interaction induced by a magnetic test body immersed into a hypersonic argon flow. The characteristic plasma parameters are measured. They are related to the voltages arising in the Hall direction and to the variation of the fluid dynamic properties induced by the interaction. The tests have been performed in a hypersonic wind tunnel at Mach 6 and Mach 15. The plasma parameters are measured in the stagnation region in front of the nozzle of the wind tunnel and in the free stream region at the nozzle exit. The test body has a conical shape with the cone axis in the gas flow direction and the cone vertex against the flow. It is placed at the nozzle exit and is equipped with three permanent magnets. In the configuration adopted, the Faraday current flows in a closed loop completely immersed into the plasma of the shock layer. The electric field and the pressure variation due to MHD interaction have been measured on the test body walls. Microwave adsorption measurements have been used for the determination of the electron number density and the electron collision frequency. Continuum recombination radiation and line radiation emissions have been detected. The electron temperature has been determined by means of the spectroscopic data by using different methods. The electron number density has been also determined by means of the Stark broadening of H α and the H β lines. Optical imaging has been utilized to visualize the pattern of the electric current distribution in the shock layer around the test body. The experiments show a considerable effect of the electromagnetic forces produced by the MHD interaction acting on the plasma flow around the test body. A comparison of the experimental data with simulation results shows a good agreement.

  11. Effect of attractive interactions between polymers on the effective force acting between colloids immersed in a polymer system: Analytic liquid-state theory.

    Science.gov (United States)

    Chervanyov, A I

    2016-12-28

    By making use of the polymer reference interaction site model, we analytically study the effect of attractive interactions between polymers on the effective forces acting between colloids immersed in a polymer system. The performed theoretical analysis has no restrictions with respect to the polymer density and relative sizes of the colloids and polymers. The polymer mediated (PM) potential acting between colloids is shown to significantly depend on the strength and range of the polymer-polymer interactions. In the nano-particle limit, where the colloid radius is much smaller than the polymer gyration radius, the presence of attractive polymer-polymer interactions causes only quantitative changes to the PM potential. In the opposite limit of relatively large colloids, the polymer-polymer interactions revert the sign of the total effective force acting between colloids so that this force becomes attractive at sufficiently large polymer densities. With the objective to study an intricate interplay between the attractive PM forces and steric repulsion in different polymer density regimes, we calculate the second virial coefficient B of the total effective potential acting between colloids. The dependence of B on the polymer density is discussed in detail, revealing several novel features of the PM interactions caused by the presence of attractive polymer-polymer interactions.

  12. Dispersion Forces

    CERN Document Server

    Buhmann, Stefan Yoshi

    2012-01-01

    In this book, a modern unified theory of dispersion forces on atoms and bodies is presented which covers a broad range of advanced aspects and scenarios. Macroscopic quantum electrodynamics is shown to provide a powerful framework for dispersion forces which allows for discussing general properties like their non-additivity and the relation between microscopic and macroscopic interactions. It is demonstrated how the general results can be used to obtain dispersion forces on atoms in the presence of bodies of various shapes and materials. Starting with a brief recapitulation of volume I, this volume II deals especially with bodies of irregular shapes, universal scaling laws, dynamical forces on excited atoms, enhanced forces in cavity quantum electrodynamics, non-equilibrium forces in thermal environments and quantum friction. The book gives both the specialist and those new to the field a thorough overview over recent results in the field. It provides a toolbox for studying dispersion forces in various contex...

  13. 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.

  14. 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.

  15. An atomic force microscope for the study of the effects of tip sample interactions on dimensional metrology

    Science.gov (United States)

    Yacoot, Andrew; Koenders, Ludger; Wolff, Helmut

    2007-02-01

    An atomic force microscope (AFM) has been developed for studying interactions between the AFM tip and the sample. Such interactions need to be taken into account when making quantitative measurements. The microscope reported here has both the conventional beam deflection system and a fibre optical interferometer for measuring the movement of the cantilever. Both can be simultaneously used so as to not only servo control the tip movements, but also detect residual movement of the cantilever. Additionally, a high-resolution homodyne differential optical interferometer is used to measure the vertical displacement between the cantilever holder and the sample, thereby providing traceability for vertical height measurements. The instrument is compatible with an x-ray interferometer, thereby facilitating high resolution one-dimensional scans in the X-direction whose metrology is based on the silicon d220 lattice spacing (0.192 nm). This paper concentrates on the first stage of the instrument's development and presents some preliminary results validating the instrument's performance and showing its potential.

  16. Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy.

    Science.gov (United States)

    Li, Mi; Liu, LianQing; Xi, Ning; Wang, YueChao; Xiao, XiuBin; Zhang, WeiJing

    2015-09-01

    Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.

  17. 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.

  18. 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.

  19. 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.

  20. Nuclear structure calculations with a sum of Sussex interaction and 3-body delta force: binding energies of closed-shell nuclei

    International Nuclear Information System (INIS)

    Singh, B.

    1978-01-01

    The Sussex matrix elements lack saturation property because of the missing short-range strong repulsion. It is demonstrated that the 3-body repulsive delta force may be used to simulate the effect of the short-range repulsion. When the delta force is added to the Sussex interaction the results are almost identical with those obtained earlier by first calculating a G-matrix from the hard core and then adding this to the old Sussex matrix elements. (author)

  1. Epifluorescence and atomic force microscopy: Two innovative applications for studying phage-host interactions in Lactobacillus helveticus.

    Science.gov (United States)

    Zago, Miriam; Scaltriti, Erika; Fornasari, Maria Emanuela; Rivetti, Claudio; Grolli, Stefano; Giraffa, Giorgio; Ramoni, Roberto; Carminati, Domenico

    2012-01-01

    Bacteriophages attacking lactic acid bacteria (LAB) still represent a crucial problem in industrial dairy fermentations. The consequences of a phage infection against LAB can lead to fermentation delay, alteration of the product quality and, in most severe cases, the product loss. Phage particles enumeration and phage-host interactions are normally evaluated by conventional plaque count assays, but, in many cases, these methods can be unsuccessful. Bacteriophages of Lactobacillus helveticus, a LAB species widely used as dairy starter or probiotic cultures, are often unable to form lysis plaques, thus impairing their enumeration by plate assay. In this study, we used epifluorescence microscopy to enumerate L. helveticus phage particles from phage-infected cultures and Atomic Force Microscopy (AFM) to visualize both phages and bacteria during the different stages of the lytic cycle. Preliminary, we tested the sensitivity of phage counting by epifluorescence microscopy. To this end, phage particles of ΦAQ113, a lytic phage of L. helveticus isolated from a whey starter culture, were stained by SYBR Green I and enumerated by epifluorescence microscopy. Values obtained by the microscopic method were 10 times higher than plate counts, with a lowest sensitivity limit of ≥6log phage/ml. The interaction of phage ΦAQ113 with its host cell L. helveticus Lh1405 was imaged by AFM after 0, 2 and 5h from phage-host adsorption. The lytic cycle was followed by epifluorescence microscopy counting and the concomitant cell wall changes were visualized by AFM imaging. Our results showed that these two methods can be combined for a reliable phage enumeration and for studying phage and host morphology during infection processes, thus giving a complete overview of phage-host interactions in L. helveticus strains involved in dairy productions. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. HapTip: Displaying Haptic Shear Forces at the Fingertips for Multi-Finger Interaction in Virtual Environments

    Directory of Open Access Journals (Sweden)

    Adrien eGirard

    2016-04-01

    Full Text Available The fingertips are one of the most important and sensitive parts of our body.They are the first stimulated areas of the hand when we interact with our environment.Providing haptic feedback to the fingertips in virtual reality could thus drastically improve perception and interaction with virtual environments.In this paper, we present a modular approach called HapTip to display such haptic sensations at the level of the fingertips.This approach relies on a wearable and compact haptic device able to simulate 2 Degree of Freedom (DoF shear forces on the fingertip with a displacement range of +/- 2 mm. Several modules can be added and used jointly in order to address multi-finger and/or bimanual scenarios in virtual environments.For that purpose, we introduce several haptic rendering techniques to cover different cases of 3D interaction such as touching a rough virtual surface, or feeling the inertia or weight of a virtual object.In order to illustrate the possibilities offered by HapTip, we provide four use cases focused on touching or grasping virtual objects.To validate the efficiency of our approach, we also conducted experiments to assess the tactile perception obtained with HapTip.Our results show that participants can successfully discriminate the directions of the 2 DoF stimulation of our haptic device.We found also that participants could well perceive different weights of virtual objects simulated using two HapTip devices. We believe that HapTip could be used in numerous applications in virtual reality for which 3D manipulation and tactile sensations are often crucial, such as in virtual prototyping or virtual training.

  3. Dual frequency modulation with two cantilevers in series: a possible means to rapidly acquire tip–sample interaction force curves with dynamic AFM

    International Nuclear Information System (INIS)

    Solares, Santiago D; Chawla, Gaurav

    2008-01-01

    One common application of atomic force microscopy (AFM) is the acquisition of tip–sample interaction force curves. However, this can be a slow process when the user is interested in studying non-uniform samples, because existing contact- and dynamic-mode methods require that the measurement be performed at one fixed surface point at a time. This paper proposes an AFM method based on dual frequency modulation using two cantilevers in series, which could be used to measure the tip–sample interaction force curves and topography of the entire sample with a single surface scan, in a time that is comparable to the time needed to collect a topographic image with current AFM imaging modes. Numerical simulation results are provided along with recommended parameters to characterize tip–sample interactions resembling those of conventional silicon tips and carbon nanotube tips tapping on silicon surfaces

  4. Recommendations of the wwPDB NMR Validation Task Force

    Science.gov (United States)

    Montelione, Gaetano T.; Nilges, Michael; Bax, Ad; Güntert, Peter; Herrmann, Torsten; Richardson, Jane S.; Schwieters, Charles; Vranken, Wim F.; Vuister, Geerten W.; Wishart, David S.; Berman, Helen M.; Kleywegt, Gerard J.; Markley, John L.

    2013-01-01

    As methods for analysis of biomolecular structure and dynamics using nuclear magnetic resonance spectroscopy (NMR) continue to advance, the resulting 3D structures, chemical shifts, and other NMR data are broadly impacting biology, chemistry, and medicine. Structure model assessment is a critical area of NMR methods development, and is an essential component of the process of making these structures accessible and useful to the wider scientific community. For these reasons, the Worldwide Protein Data Bank (wwPDB) has convened an NMR Validation Task Force (NMR-VTF) to work with the wwPDB partners in developing metrics and policies for biomolecular NMR data harvesting, structure representation, and structure quality assessment. This paper summarizes the recommendations of the NMR-VTF, and lays the groundwork for future work in developing standards and metrics for biomolecular NMR structure quality assessment. PMID:24010715

  5. 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

  6. Toxic cocaine- and convulsant-induced modification of forced swimming behaviors and their interaction with ethanol: comparison with immobilization stress

    Science.gov (United States)

    Hayase, Tamaki; Yamamoto, Yoshiko; Yamamoto, Keiichi

    2002-01-01

    Background Swimming behaviors in the forced swimming test have been reported to be depressed by stressors. Since toxic convulsion-inducing drugs related to dopamine [cocaine (COC)], benzodiazepine [methyl 6,7-dimethoxy-4-ethyl-β-carboline-carboxylate (DMCM)], γ-aminobutyric acid (GABA) [bicuculline (BIC)], and glutamate [N-methyl-D-aspartate (NMDA)] receptors can function as stressors, the present study compared their effects on the forced swimming behaviors with the effects of immobilization stress (IM) in rats. Their interactions with ethanol (EtOH), the most frequently coabused drug with COC which also induces convulsions as withdrawal symptoms but interferes with the convulsions caused by other drugs, were also investigated. Results Similar to the IM (10 min) group, depressed swimming behaviors (attenuated time until immobility and activity counts) were observed in the BIC (5 mg/kg IP) and DMCM (10 mg/kg IP) groups at the 5 h time point, after which no toxic behavioral symptoms were observed. However, they were normalized to the control levels at the 12 h point, with or without EtOH (1.5 g/kg IP). In the COC (60 mg/kg IP) and NMDA (200 mg/kg IP) groups, the depression occurred late (12 h point), and was normalized by the EtOH cotreatment. At the 5 h point, the COC treatment enhanced the swimming behaviors above the control level. Conclusions Although the physiological stress (IM), BIC, and DMCM also depressed the swimming behaviors, a delayed occurrence and EtOH-induced recovery of depressed swimming were observed only in the COC and NMDA groups. This might be correlated with the previously-reported delayed responses of DA and NMDA neurons rather than direct effects of the drugs, which could be suppressed by EtOH. Furthermore, the characteristic psychostimulant effects of COC seemed to be correlated with an early enhancement of swimming behaviors. PMID:12425723

  7. MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance

    Directory of Open Access Journals (Sweden)

    Moscetti I

    2016-08-01

    Full Text Available Ilaria Moscetti,1 Emanuela Teveroni,2,3 Fabiola Moretti,3 Anna Rita Bizzarri,1 Salvatore Cannistraro1 1Biophysics and Nanoscience Centre, Department DEB, Università della Tuscia, Viterbo, Italy; 2Department of Endocrinology and Metabolism, Università Cattolica di Roma, Roma, Italy; 3Institute of Cell Biology and Neurobiology, Consiglio Nazionale delle Ricerche (CNR, Roma, Italy Abstract: Murine double minute 2 (MDM2 and 4 (MDM4 are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2–MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2–MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD in the micromolar range for the MDM2–MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2–MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2–MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation. Keywords: MDM2, MDM4, atomic force spectroscopy, surface plasmon resonance

  8. Biomolecule recognition using piezoresistive nanomechanical force probes

    Science.gov (United States)

    Tosolini, Giordano; Scarponi, Filippo; Cannistraro, Salvatore; Bausells, Joan

    2013-06-01

    Highly sensitive sensors are one of the enabling technologies for the biomarker detection in early stage diagnosis of pathologies. We have developed a self-sensing nanomechanical force probe able for detecting the unbinding of single couples of biomolecular partners in nearly physiological conditions. The embedding of a piezoresistive transducer into a nanomechanical cantilever enabled high force measurement capability with sub 10-pN resolution. Here, we present the design, microfabrication, optimization, and complete characterization of the sensor. The exceptional electromechanical performance obtained allowed us to detect biorecognition specific events underlying the biotin-avidin complex formation, by integrating the sensor in a commercial atomic force microscope.

  9. Myofascial force transmission causes interaction between adjacent muscles and connective tissue: Effects of blunt dissection and compartmental fasciotomy on length force characteristics of rat extensor digitorum longus muscle

    NARCIS (Netherlands)

    Huijing, P.A.J.B.M.; Baan, G.C.

    2001-01-01

    Muscles within the anterior tibial compartment (extensor digitorum longus: EDL. tibialis anterior: TA, and extensor hallucis longus muscles: EHL) and within the peroneal compartment were excited simultaneously and maximally. The ankle joint was fixed kept at 90°. For EDL length force characteristics

  10. Problems of organization of interaction of administrative bodies and the forces engaged in liquidation of after-effects of radiation accident

    International Nuclear Information System (INIS)

    Popov, A.P.; Perevezentsev, A.M.

    1995-01-01

    The paper defines the main problems arising in connection with organization of interaction of the administrative bodies and the forces involved in liquidation of after-effects of radiation accident. It is demonstrated that in order to increase the efficiency of interaction of the administrative bodies of various levels it is necessary to make it automatic. The paper revealed the meaning of the levels of relationship between various automatic systems. 4 refs

  11. Examining platelet-fibrin interactions during traumatic shock in a swine model using platelet contractile force and clot elastic modulus.

    Science.gov (United States)

    White, Nathan J; Martin, Erika J; Brophy, Donald F; Ward, Kevin R

    2011-07-01

    A significant proportion of severely injured patients develop early coagulopathy, characterized by abnormal clot formation, which impairs resuscitation and increases mortality. We have previously demonstrated an isolated decrease in clot strength by thrombelastography in a swine model of nonresuscitated traumatic shock. In order to more closely examine platelet-fibrin interactions in this setting, we define the observed decrease in clot strength in terms of platelet-induced clot contraction and clot elastic modulus using the Hemostasis Analysis System (HAS) (Hemodyne Inc., Richmond, Virginia, USA). Whole blood was sampled for HAS measurements, metabolic measurements, cell counts, and fibrinogen concentration at baseline prior to injury and again at a predetermined level of traumatic shock defined by oxygen debt. Male swine (N=17) received femur fracture and controlled arterial hemorrhage to achieve an oxygen debt of 80 ml/kg. Platelet counts were unchanged, but fibrinogen concentration was reduced significantly during shock (167.6 vs. 66.7 mg/dl, P=0.0007). Platelet contractile force generated during clot formation did not change during shock (11.7 vs. 10.4 kdynes, P=0.41), but clot elastic modulus was dynamically altered, resulting in a lower final value (22.9 vs. 17.3 kdynes/cm, Pshock, platelet function was preserved, whereas terminal clot elastic modulus was reduced during shock in a manner most consistent with early changes in the mechanical properties of the developing fibrin fiber network.

  12. MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance

    Science.gov (United States)

    Moscetti, Ilaria; Teveroni, Emanuela; Moretti, Fabiola; Bizzarri, Anna Rita; Cannistraro, Salvatore

    2016-01-01

    Murine double minute 2 (MDM2) and 4 (MDM4) are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2–MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2–MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD) in the micromolar range for the MDM2–MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2–MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2–MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation. PMID:27621617

  13. On Extension of the Current Biomolecular Empirical Force Field for the Description of Halogen Bonds

    Czech Academy of Sciences Publication Activity Database

    Kolář, Michal; Hobza, Pavel

    2012-01-01

    Roč. 8, č. 4 (2012), s. 1325-1333 ISSN 1549-9618 R&D Projects: GA ČR GBP208/12/G016 Grant - others:European Science Fund(XE) CZ.1.05/2.1.00/03.0058 Institutional research plan: CEZ:AV0Z40550506 Keywords : halogen bond * molecular mechanics * sigma-hole Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.389, year: 2012

  14. Physical Forces between Humans and How Humans Attract and Repel Each Other Based on Their Social Interactions in an Online World.

    Directory of Open Access Journals (Sweden)

    Stefan Thurner

    Full Text Available Physical interactions between particles are the result of the exchange of gauge bosons. Human interactions are mediated by the exchange of messages, goods, money, promises, hostilities, etc. While in the physical world interactions and their associated forces have immediate dynamical consequences (Newton's laws the situation is not clear for human interactions. Here we quantify the relative acceleration between humans who interact through the exchange of messages, goods and hostilities in a massive multiplayer online game. For this game we have complete information about all interactions (exchange events between about 430,000 players, and about their trajectories (movements in the metric space of the game universe at any point in time. We use this information to derive "interaction potentials" for communication, trade and attacks and show that they are harmonic in nature. Individuals who exchange messages and trade goods generally attract each other and start to separate immediately after exchange events end. The form of the interaction potential for attacks mirrors the usual "hit-and-run" tactics of aggressive players. By measuring interaction intensities as a function of distance, velocity and acceleration, we show that "forces" between players are directly related to the number of exchange events. We find an approximate power-law decay of the likelihood for interactions as a function of distance, which is in accordance with previous real world empirical work. We show that the obtained potentials can be understood with a simple model assuming an exchange-driven force in combination with a distance-dependent exchange rate.

  15. Effect of Withania somnifera on forced swimming test induced immobility in mice and its interaction with various drugs.

    Science.gov (United States)

    Shah, P C; Trivedi, N A; Bhatt, J D; Hemavathi, K G

    2006-01-01

    The objective of the present study was to evaluate the antidepressant action of Withania somnifera (WS) as well as its interaction with the conventional antidepressant drugs and to delineate the possible mechanism of its antidepressant action using forced swimming model in mice. Effect of different doses of WS, fluoxetine and imipramine were studied on forced swimming test induced mean immobility time (MIT). Moreover effect of WS 100 mg/kg, i.p. was observed at different time intervals. Effect produced by combination of sub therapeutic doses of WS with imipramine (2.5 mg/kg, i.p.) as well as fluoxetine (2.5 mg/kg, i.p.) were also observed. Effect of WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) were observed in mice pretreated with reserpine (2 mg/kg, i.p.) and clonidine (0.15 mg/kg, i.p.). Effects of prazosin (3 mg/kg, i.p.) or haloperidol (0.1 mg/kg, i.p.) pre-treatment were also observed on WS induced decrease in MIT. WS produced dose dependent decrease in MIT. Maximum effect in MIT was observed after 30 min of treatment with WS 100 mg/kg, i.p. Combination of WS (37.5 mg/kg, i.p.) with imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) also produced significant decrease in the MIT. Clonidine and reserpine induced increase in MIT, was significantly reversed by treatment with WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.). Pre-treatment with prazosin but not haloperidol, significantly antagonized the WS (100 mg/kg, i.p.) induced decrease in MIT. It is concluded that, WS produced significant decrease in MIT in mice which could be mediated partly through a adrenoceptor as well as alteration in the level of central biogenic amines.

  16. Coupling effects of refractive index discontinuity, spot size and spot location on the deflection sensitivity of optical-lever based atomic force microscopy

    International Nuclear Information System (INIS)

    Liu Yu; Yang Jun

    2008-01-01

    Atomic force microscopy (AFM) plays an essential role in nanotechnology and nanoscience. The recent advances of AFM in bionanotechnology include phase imaging of living cells and detection of biomolecular interactions in liquid biological environments. Deflection sensitivity is a key factor in both imaging and force measurement, which is significantly affected by the coupling effects of the refractive index discontinuity between air, the glass window and the liquid medium, and the laser spot size and spot location. The effects of both the spot size and the spot location on the sensitivity are amplified by the refractive index discontinuity. The coupling effects may govern a transition of the deflection sensitivity from enhancement to degradation. It is also found that there is a critical value for the laser spot size, above which the deflection sensitivity is mainly determined by the refractive index of the liquid. Experimental results, in agreement with theoretical predication, elucidate the coupling effects

  17. Optimizing Solute-Solute Interactions in the GLYCAM06 and CHARMM36 Carbohydrate Force Fields Using Osmotic Pressure Measurements.

    Science.gov (United States)

    Lay, Wesley K; Miller, Mark S; Elcock, Adrian H

    2016-04-12

    GLYCAM06 and CHARMM36 are successful force fields for modeling carbohydrates. To correct recently identified deficiencies with both force fields, we adjusted intersolute nonbonded parameters to reproduce the experimental osmotic coefficient of glucose at 1 M. The modified parameters improve behavior of glucose and sucrose up to 4 M and improve modeling of a dextran 55-mer. While the modified parameters may not be applicable to all carbohydrates, they highlight the use of osmotic simulations to optimize force fields.

  18. 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

  19. Characterizing interaction forces between actin and proteins of the tropomodulin family reveals the presence of the N-terminal actin-binding site in leiomodin.

    Science.gov (United States)

    Arslan, Baran; Colpan, Mert; Gray, Kevin T; Abu-Lail, Nehal I; Kostyukova, Alla S

    2018-01-15

    Tropomodulin family of proteins includes several isoforms of tropomodulins (Tmod) and leiomodins (Lmod). These proteins can sequester actin monomers or nucleate actin polymerization. Although it is known that their actin-binding properties are isoform-dependent, knowledge on how they vary in strengths of interactions with G-actin is missing. While it is confirmed in many studies that Tmods have two actin-binding sites, information on number and location of actin-binding sites in Lmod2 is controversial. We used atomic force microscopy to study interactions between G-actin and proteins of the tropomodulin family. Unbinding forces between G-actin and Tmod1, Tmod2, Tmod3, or Lmod2 were quantified. Our results indicated that Tmod1 and Tmod3 had unimodal force distributions, Tmod2 had a bimodal distribution and Lmod2 had a trimodal distribution. The number of force distributions correlates with the proteins' abilities to sequester actin or to nucleate actin polymerization. We assigned specific unbinding forces to the individual actin-binding sites of Tmod2 and Lmod2 using mutations that destroy actin-binding sites of Tmod2 and truncated Lmod2. Our results confirm the existence of the N-terminal actin-binding site in Lmod2. Altogether, our data demonstrate how the differences between the number and the strength of actin-binding sites of Tmod or Lmod translate to their functional abilities. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Influence of the density dependence factor in effective nucleon-nucleon forces and interaction of 4He-particles with stable nuclei

    International Nuclear Information System (INIS)

    Kuterbekov, K.A.; Zholdybayev, T.K.; Muchamedzhan, A.; Penionzhkevich, Yu.E.; Kukhtina, I.N.

    2004-01-01

    Full text: The most popular method for join analysis of experimental angular distributions (AD) and total cross sections (TCS) at low and moderate energies is semimicroscopic folding model (SFM) [1]. Since 4 He-particle is a core of exotic nuclei 6,8 He, it is topical to continue systematic investigations at various effective nucleon-nucleon forces. In [2] we investigated for the first time energy and mass dependencies of the parameters SFM at low and moderate energies. At that, as effective forces between nucleons of the colliding nuclei were used total M3Y-interaction [3] and nucleon densities calculated by the method of density functional [4]. In the present work based on SFM there were investigated influences of the density dependence factor in effective nucleon-nucleon forces (4 force options considered) on calculation of ADs and TCSs at interaction of 4 He-particles with stable nuclei (A = 12 - 208) at α-particle energies 21 - 141.5 MeV. Corresponding experimental AD and TCS data used for model verification are of high quality with low error both for angular and energy diapason. Therefore, conclusions made in the performed investigation contain important quantitative information and are valuable for consequent comparative analysis of experimental data on interaction of light exotic nuclei with stable nuclei

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. Analysis of the forced vibration test of the Hualien large scale soil-structure interaction model using a flexible volume substructuring method

    International Nuclear Information System (INIS)

    Tang, H.T.; Nakamura, N.

    1995-01-01

    A 1/4-scale cylindrical reactor containment model was constructed in Hualien, Taiwan for foil-structure interaction (SSI) effect evaluation and SSI analysis procedure verification. Forced vibration tests were executed before backfill (FVT-1) and after backfill (FVT-2) to characterize soil-structure system characteristics under low excitations. A number of organizations participated in the pre-test blind prediction and post-test correlation analyses of the forced vibration test using various industry familiar methods. In the current study, correlation analyses were performed using a three-dimensional flexible volume substructuring method. The results are reported and soil property sensitivities are evaluated in the paper. (J.P.N.)

  6. Fabrication of robot head module using contact resistance force sensor for human robot interaction and its evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Ki; Kim, Jong Ho [Korea Reserch Institute of Standards and Science, Daejeon (Korea, Republic of); Kwon, Hyun Joon [Univ. of Maryland, Maryland (United States); Kwon, Young Ha [Kyung Hee Univ., Gyunggi Do (Korea, Republic of)

    2012-10-15

    This paper presents a design of a robot head module with touch sensing algorithms that can simultaneously detect contact force and location. The module is constructed with a hemisphere and three sensor units that are fabricated using contact resistance force sensors. The surface part is designed with the hemisphere that measures 300 mm in diameter and 150 mm in height. Placed at the bottom of the robot head module are three sensor units fabricated using a simple screen printing technique. The contact force and the location of the model are evaluated through the calibration setup. The experiment showed that the calculated contact positions almost coincided with the applied load points as the contact location changed with a location error of about {+-}8.67 mm. The force responses of the module were evaluated at two points under loading and unloading conditions from 0 N to 5 N. The robot head module showed almost the same force responses at the two points.

  7. 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.

  8. 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…

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-10-24

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

  10. 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

  11. Antigen-antibody biorecognition events as discriminated by noise analysis of force spectroscopy curves.

    Science.gov (United States)

    Bizzarri, Anna Rita; Cannistraro, Salvatore

    2014-08-22

    Atomic force spectroscopy is able to extract kinetic and thermodynamic parameters of biomolecular complexes provided that the registered unbinding force curves could be reliably attributed to the rupture of the specific complex interactions. To this aim, a commonly used strategy is based on the analysis of the stretching features of polymeric linkers which are suitably introduced in the biomolecule-substrate immobilization procedure. Alternatively, we present a method to select force curves corresponding to specific biorecognition events, which relies on a careful analysis of the force fluctuations of the biomolecule-functionalized cantilever tip during its approach to the partner molecules immobilized on a substrate. In the low frequency region, a characteristic 1/f (α) noise with α equal to one (flickering noise) is found to replace white noise in the cantilever fluctuation power spectrum when, and only when, a specific biorecognition process between the partners occurs. The method, which has been validated on a well-characterized antigen-antibody complex, represents a fast, yet reliable alternative to the use of linkers which may involve additional surface chemistry and reproducibility concerns.

  12. Propulsion and airframe aerodynamic interactions of supersonic V/STOL configurations. Volume 2: Wind tunnel test force and moment data report

    Science.gov (United States)

    Zilz, D. E.

    1985-01-01

    A wind tunnel model of a supersonic V/STOL fighter configuration has been tested to measure the aerodynamic interaction effects which can result from geometrically close-coupled propulsion system/airframe components. The approach was to configure the model to represent two different test techniques. One was a conventional test technique composed of two test modes. In the Flow-Through mode, absolute configuration aerodynamics are measured, including inlet/airframe interactions. In the Jet-Effects mode, incremental nozzle/airframe interactions are measured. The other test technique is a propulsion simulator approach, where a sub-scale, externally powered engine is mounted in the model. This allows proper measurement of inlet/airframe and nozzle/airframe interactions simultaneously. This is Volume 2 of 2: Wind Tunnel Test Force and Moment Data Report.

  13. Equivalence of Electron-Vibration Interaction and Charge-Induced Force Variations: A New O(1 Approach to an Old Problem

    Directory of Open Access Journals (Sweden)

    Tunna Baruah

    2012-04-01

    Full Text Available Calculating electron-vibration (vibronic interaction constants is computationally expensive. For molecules containing N nuclei it involves solving the Schrödinger equation for Ο(3N nuclear configurations in addition to the cost of determining the vibrational modes. We show that quantum vibronic interactions are proportional to the classical atomic forces induced when the total charge of the system is varied. This enables the calculation of vibronic interaction constants from O(1 solutions of the Schrödinger equation. We demonstrate that the O(1 approach produces numerically accurate results by calculating the vibronic interaction constants for several molecules. We investigate the role of molecular vibrations in the Mott transition in κ-(BEDT-TTF2Cu[N(CN2]Br.

  14. Polarizable Force Field for DNA Based on the Classical Drude Oscillator: I. Refinement Using Quantum Mechanical Base Stacking and Conformational Energetics.

    Science.gov (United States)

    Lemkul, Justin A; MacKerell, Alexander D

    2017-05-09

    Empirical force fields seek to relate the configuration of a set of atoms to its energy, thus yielding the forces governing its dynamics, using classical physics rather than more expensive quantum mechanical calculations that are computationally intractable for large systems. Most force fields used to simulate biomolecular systems use fixed atomic partial charges, neglecting the influence of electronic polarization, instead making use of a mean-field approximation that may not be transferable across environments. Recent hardware and software developments make polarizable simulations feasible, and to this end, polarizable force fields represent the next generation of molecular dynamics simulation technology. In this work, we describe the refinement of a polarizable force field for DNA based on the classical Drude oscillator model by targeting quantum mechanical interaction energies and conformational energy profiles of model compounds necessary to build a complete DNA force field. The parametrization strategy employed in the present work seeks to correct weak base stacking in A- and B-DNA and the unwinding of Z-DNA observed in the previous version of the force field, called Drude-2013. Refinement of base nonbonded terms and reparametrization of dihedral terms in the glycosidic linkage, deoxyribofuranose rings, and important backbone torsions resulted in improved agreement with quantum mechanical potential energy surfaces. Notably, we expand on previous efforts by explicitly including Z-DNA conformational energetics in the refinement.

  15. Nuclear forces

    International Nuclear Information System (INIS)

    Holinde, K.

    1990-01-01

    In this paper the present status of the meson theory of nuclear forces is reviewed. After some introductory remarks about the relevance of the meson exchange concept in the era of QCD and the empirical features of the NN interaction, the exciting history of nuclear forces is briefly outlined. In the main part, the author gives the basic physical ideas and sketch the derivation of the one-boson-exchange model of the nuclear force, in the Feynman approach. Secondly we describe, in a qualitative way, various necessary extensions, leading to the Bonn model of the N interaction. Finally, points to some interesting pen questions connected with the extended quark structure of the hadrons, which are topics of current research activity

  16. Single-molecule studies of DNA transcription using atomic force microscopy

    International Nuclear Information System (INIS)

    Billingsley, Daniel J; Crampton, Neal; Thomson, Neil H; Bonass, William A; Kirkham, Jennifer

    2012-01-01

    Atomic force microscopy (AFM) can detect single biomacromolecules with a high signal-to-noise ratio on atomically flat biocompatible support surfaces, such as mica. Contrast arises from the innate forces and therefore AFM does not require imaging contrast agents, leading to sample preparation that is relatively straightforward. The ability of AFM to operate in hydrated environments, including humid air and aqueous buffers, allows structure and function of biological and biomolecular systems to be retained. These traits of the AFM are ensuring that it is being increasingly used to study deoxyribonucleic acid (DNA) structure and DNA–protein interactions down to the secondary structure level. This report focuses in particular on reviewing the applications of AFM to the study of DNA transcription in reductionist single-molecule bottom-up approaches. The technique has allowed new insights into the interactions between ribonucleic acid (RNA) polymerase to be gained and enabled quantification of some aspects of the transcription process, such as promoter location, DNA wrapping and elongation. More recently, the trend is towards studying the interactions of more than one enzyme operating on a single DNA template. These methods begin to reveal the mechanics of gene expression at the single-molecule level and will enable us to gain greater understanding of how the genome is transcribed and translated into the proteome. (topical review)

  17. Multiple time step molecular dynamics in the optimized isokinetic ensemble steered with the molecular theory of solvation: Accelerating with advanced extrapolation of effective solvation forces

    International Nuclear Information System (INIS)

    Omelyan, Igor; Kovalenko, Andriy

    2013-01-01

    We develop efficient handling of solvation forces in the multiscale method of multiple time step molecular dynamics (MTS-MD) of a biomolecule steered by the solvation free energy (effective solvation forces) obtained from the 3D-RISM-KH molecular theory of solvation (three-dimensional reference interaction site model complemented with the Kovalenko-Hirata closure approximation). To reduce the computational expenses, we calculate the effective solvation forces acting on the biomolecule by using advanced solvation force extrapolation (ASFE) at inner time steps while converging the 3D-RISM-KH integral equations only at large outer time steps. The idea of ASFE consists in developing a discrete non-Eckart rotational transformation of atomic coordinates that minimizes the distances between the atomic positions of the biomolecule at different time moments. The effective solvation forces for the biomolecule in a current conformation at an inner time step are then extrapolated in the transformed subspace of those at outer time steps by using a modified least square fit approach applied to a relatively small number of the best force-coordinate pairs. The latter are selected from an extended set collecting the effective solvation forces obtained from 3D-RISM-KH at outer time steps over a broad time interval. The MTS-MD integration with effective solvation forces obtained by converging 3D-RISM-KH at outer time steps and applying ASFE at inner time steps is stabilized by employing the optimized isokinetic Nosé-Hoover chain (OIN) ensemble. Compared to the previous extrapolation schemes used in combination with the Langevin thermostat, the ASFE approach substantially improves the accuracy of evaluation of effective solvation forces and in combination with the OIN thermostat enables a dramatic increase of outer time steps. We demonstrate on a fully flexible model of alanine dipeptide in aqueous solution that the MTS-MD/OIN/ASFE/3D-RISM-KH multiscale method of molecular dynamics

  18. 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.

  19. 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.

  20. Casimir force, excess free energy and C-function in O(n) systems with long-range interactions in the n → ∞ limit

    International Nuclear Information System (INIS)

    Chamati, H.; Dantchev, D.M.

    2004-06-01

    We present exact results on the behavior of the thermodynamic Casimir force and the excess free energy and the C-function in the framework of the d-dimensional spherical model with a power law long-range interaction decaying at large distances r as r -d- σ, where σ c , as well as for T > Tc and T c . The universal finite-size scaling function governing the behavior of the force in the critical region is derived and its asymptotics are investigated. While in the critical and under -d -d-, critical region the force is of the order of L -d , for T > T c it decays as L -dσ , where L is the thickness of the film. We consider both the case of a finite system that has no phase transition of its own, when d - σ when one observes a dimensional crossover from d to a d - 1 dimensional critical behavior. The behavior of the force along the phase coexistence line for a magnetic field H = 0 and T c . is also derived. We have proven analytically that the excess free energy is always negative ad monotonically increasing function of T and H, while the C-function is always non-negative and monotonically decreasing function of T and H. For the Casimir force we have demonstrated that for any σ > it is everywhere negative, i.e. an attraction between the surfaces bounding the system is to be observed. At T = T c the force is an increasing function of T for σ > 1 and a decreasing one for σ c is always achieved at some H ≠ 0 . (author)

  1. Single molecule force spectroscopy for in-situ probing oridonin inhibited ROS-mediated EGF-EGFR interactions in living KYSE-150 cells.

    Science.gov (United States)

    Pi, Jiang; Jin, Hua; Jiang, Jinhuan; Yang, Fen; Cai, Huaihong; Yang, Peihui; Cai, Jiye; Chen, Zheng W

    2017-05-01

    As the active anticancer component of Rabdosia Rubescens, oridonin has been proved to show strong anticancer activity in cancer cells, which is also found to be closely related to its specific inhibition effects on the EGFR tyrosine kinase activity. In this study, atomic force microscopy based single molecule force spectroscopy (AFM-SMFS) was used for real-time and in-situ detection of EGF-EGFR interactions in living esophageal cancer KYSE-150 cells to evaluate the anticancer activity of oridonin for the first time. Oridonin was found to induce apoptosis and also reduce EGFR expression in KYSE-150 cells. AFM-SMFS results demonstrated that oridonin could inhibit the binding between EGF and EGFR in KYSE-150 cells by decreasing the unbinding force and binding probability for EGF-EGFR complexes, which was further proved to be closely associated with the intracellular ROS level. More precise mechanism studies based on AFM-SMFS demonstrated that oridonin treatment could decrease the energy barrier width, increase the dissociation off rate constant and decrease the activation energy of EGF-EGFR complexes in ROS dependent way, suggesting oridonin as a strong anticancer agent targeting EGF-EGFR interactions in cancer cells through ROS dependent mechanism. Our results not only suggested oridonin as a strong anticancer agent targeting EGF-EGFR interactions in ROS dependent mechanism, but also highlighted AFM-SMFS as a powerful technique for pharmacodynamic studies by detecting ligand-receptor interactions, which was also expected to be developed into a promising tool for the screening and mechanism studies of drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Haptic Human-Human Interaction Through a Compliant Connection Does Not Improve Motor Learning in a Force Field

    NARCIS (Netherlands)

    Beckers, Niek; Keemink, Arvid; van Asseldonk, Edwin; van der Kooij, Herman; Prattichizzo, Domenico; Shinoda, Hiroyuki; Tan, Hong Z.; Ruffaldi, Emanuele; Frisoli, Antonio

    2018-01-01

    Humans have a natural ability to haptically interact with other humans, for instance during physically assisting a child to learn how to ride a bicycle. A recent study has shown that haptic human-human interaction can improve individual motor performance and motor learning rate while learning to

  3. 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

    -established field are several emerging technologies with innovative mechanisms and functions that utilize the mixed ionic/electronic conducting character of conjugated organic materials. These techniques are based around flexible or printed electronics. Ionic functionalization influences many of the key properties of conductive polymers through its impacts on molecular order, the injection and transport of charge, optical excitations, and interactions with other molecules. Consequently, it is an important tool in the development of electronic and photonic devices based on conductive polymers. We have considered that to focus exclusively on the iontronics, ionic carriers in organic electronic materials and devices in organic electronic materials seems timely. Therefore, this report reviews the scientific understanding and important scientific discoveries made in the electrochemistry of conductive polymers based on our experience. The main purpose of IJEGMBE is to provide an opportunity for researchers, who are interested in biomolecular electronics and organic nanotechnology for environmental preservation, to come together in an informal and friendly atmosphere and exchange their technical information and experience. We are sure that this meeting will be very useful and fruitful for all participants to summarize the recent progress in biomolecular electronics and organic nanotechnology for environmental preservation and prepare the next step for future generations. Many papers have been submitted from India and Japan and more than 20 papers have been accepted for presentation. All the papers accepted will be presented. The main topics of interest are as follows; Bioelectronics Biomolecular Electronics Fabrication Techniques Self-assembled monolayers Nano sensors Environmental monitoring Organic devices Organic Functional Materials Others The program of this meeting consists of Invited Lectures and oral presentations. We hope all participants benefited from this meeting. We would

  4. Design principles for high–pressure force fields: Aqueous TMAO solutions from ambient to kilobar pressures

    Energy Technology Data Exchange (ETDEWEB)

    Hölzl, Christoph; Horinek, Dominik, E-mail: dominik.horinek@ur.de [Institut für Physikalische und Theoretische Chemie, Universität Regensburg, 93040 Regensburg (Germany); Kibies, Patrick; Frach, Roland; Kast, Stefan M., E-mail: stefan.kast@tu-dortmund.de [Physikalische Chemie III, Technische Universität Dortmund, 44227 Dortmund (Germany); Imoto, Sho, E-mail: sho.imoto@theochem.rub.de; Marx, Dominik [Lehrstuhl für Theoretische Chemie, Ruhr-Universität Bochum, 44780 Bochum (Germany); Suladze, Saba; Winter, Roland [Physikalische Chemie I, Technische Universität Dortmund, 44227 Dortmund (Germany)

    2016-04-14

    Accurate force fields are one of the major pillars on which successful molecular dynamics simulations of complex biomolecular processes rest. They have been optimized for ambient conditions, whereas high-pressure simulations become increasingly important in pressure perturbation studies, using pressure as an independent thermodynamic variable. Here, we explore the design of non-polarizable force fields tailored to work well in the realm of kilobar pressures – while avoiding complete reparameterization. Our key is to first compute the pressure-induced electronic and structural response of a solute by combining an integral equation approach to include pressure effects on solvent structure with a quantum-chemical treatment of the solute within the embedded cluster reference interaction site model (EC-RISM) framework. Next, the solute’s response to compression is taken into account by introducing pressure-dependence into selected parameters of a well-established force field. In our proof-of-principle study, the full machinery is applied to N,N,N-trimethylamine-N-oxide (TMAO) in water being a potent osmolyte that counteracts pressure denaturation. EC-RISM theory is shown to describe well the charge redistribution upon compression of TMAO(aq) to 10 kbar, which is then embodied in force field molecular dynamics by pressure-dependent partial charges. The performance of the high pressure force field is assessed by comparing to experimental and ab initio molecular dynamics data. Beyond its broad usefulness for designing non-polarizable force fields for extreme thermodynamic conditions, a good description of the pressure-response of solutions is highly recommended when constructing and validating polarizable force fields.

  5. Design principles for high-pressure force fields: Aqueous TMAO solutions from ambient to kilobar pressures.

    Science.gov (United States)

    Hölzl, Christoph; Kibies, Patrick; Imoto, Sho; Frach, Roland; Suladze, Saba; Winter, Roland; Marx, Dominik; Horinek, Dominik; Kast, Stefan M

    2016-04-14

    Accurate force fields are one of the major pillars on which successful molecular dynamics simulations of complex biomolecular processes rest. They have been optimized for ambient conditions, whereas high-pressure simulations become increasingly important in pressure perturbation studies, using pressure as an independent thermodynamic variable. Here, we explore the design of non-polarizable force fields tailored to work well in the realm of kilobar pressures--while avoiding complete reparameterization. Our key is to first compute the pressure-induced electronic and structural response of a solute by combining an integral equation approach to include pressure effects on solvent structure with a quantum-chemical treatment of the solute within the embedded cluster reference interaction site model (EC-RISM) framework. Next, the solute's response to compression is taken into account by introducing pressure-dependence into selected parameters of a well-established force field. In our proof-of-principle study, the full machinery is applied to N,N,N-trimethylamine-N-oxide (TMAO) in water being a potent osmolyte that counteracts pressure denaturation. EC-RISM theory is shown to describe well the charge redistribution upon compression of TMAO(aq) to 10 kbar, which is then embodied in force field molecular dynamics by pressure-dependent partial charges. The performance of the high pressure force field is assessed by comparing to experimental and ab initio molecular dynamics data. Beyond its broad usefulness for designing non-polarizable force fields for extreme thermodynamic conditions, a good description of the pressure-response of solutions is highly recommended when constructing and validating polarizable force fields.

  6. Design principles for high–pressure force fields: Aqueous TMAO solutions from ambient to kilobar pressures

    International Nuclear Information System (INIS)

    Hölzl, Christoph; Horinek, Dominik; Kibies, Patrick; Frach, Roland; Kast, Stefan M.; Imoto, Sho; Marx, Dominik; Suladze, Saba; Winter, Roland

    2016-01-01

    Accurate force fields are one of the major pillars on which successful molecular dynamics simulations of complex biomolecular processes rest. They have been optimized for ambient conditions, whereas high-pressure simulations become increasingly important in pressure perturbation studies, using pressure as an independent thermodynamic variable. Here, we explore the design of non-polarizable force fields tailored to work well in the realm of kilobar pressures – while avoiding complete reparameterization. Our key is to first compute the pressure-induced electronic and structural response of a solute by combining an integral equation approach to include pressure effects on solvent structure with a quantum-chemical treatment of the solute within the embedded cluster reference interaction site model (EC-RISM) framework. Next, the solute’s response to compression is taken into account by introducing pressure-dependence into selected parameters of a well-established force field. In our proof-of-principle study, the full machinery is applied to N,N,N-trimethylamine-N-oxide (TMAO) in water being a potent osmolyte that counteracts pressure denaturation. EC-RISM theory is shown to describe well the charge redistribution upon compression of TMAO(aq) to 10 kbar, which is then embodied in force field molecular dynamics by pressure-dependent partial charges. The performance of the high pressure force field is assessed by comparing to experimental and ab initio molecular dynamics data. Beyond its broad usefulness for designing non-polarizable force fields for extreme thermodynamic conditions, a good description of the pressure-response of solutions is highly recommended when constructing and validating polarizable force fields.

  7. Analysis the dynamic response of earth dam in free vibration and forced by introducing the effect of the interaction dam foundation

    Directory of Open Access Journals (Sweden)

    Malika Boumaiza

    2018-01-01

    Full Text Available The present study concerns the analysis of the dynamic response of earth dam, in free and forced vibration (under the effect of earthquake using the finite element method. The analysis is carried out at the end of dam construction without filling. The behavior of the dam materials and the foundation is linear elastic. In free vibration, to better understand the effect of the dam foundation interaction, we will take into account different site conditions and see their influence on the free vibration characteristics of the dam. In forced vibration, to study the seismic response of the dam, the system is subjected to the acceleration of the Boumerdes earthquake of May 21, 2003 recorded at the station n ° 2 of the dam of Kaddara in the base, with a parametric study taking into account the influence of the main parameters such as the mechanical properties of the soil: rigidity, density.

  8. Remote ENSO forcing versus local air-sea interaction in QTCM: a sensitivity study to intraseasonal variability

    Directory of Open Access Journals (Sweden)

    D. Gushchina

    2006-01-01

    Full Text Available The skill of a newly designed global atmospheric model of intermediate complexity - QTCM (for quasi-equilibrium tropical circulation model in simulating the teleconnections is investigated. The role of the ENSO remote forcing over the Pacific surrounding regions is emphasized from sensitivity experiments to critical parameters of the model. The role of the tropical intraseasonal variability (ITV on the simulated ENSO teleconnection pattern is estimated using the methodology proposed by Lin et al. (2000 allowing to damp the energy of ITV in the model. The reduction of intraseasonal variability allows emphasizing the forced response of the atmosphere and eases the detection of local coupled atmosphere-ocean patterns. It was shown that the simulated ITV has an impact on the ENSO teleconnection pattern both in the mid-latitudes and in regions of ascending and descending branches of Walker circulation cells in the tropics.

  9. Multicolor Fluorescence Writing Based on Host-Guest Interactions and Force-Induced Fluorescence-Color Memory.

    Science.gov (United States)

    Matsunaga, Yuki; Yang, Jye-Shane

    2015-06-26

    A new strategy is reported for multicolor fluorescence writing on thin solid films with mechanical forces. This concept is illustrated by the use of a green-fluorescent pentiptycene derivative 1, which forms variably colored fluorescent exciplexes: a change from yellow to red was observed with anilines, and fluorescence quenching (a change to black) occurred in the presence of benzoquinone. Mechanical forces, such as grinding and shearing, induced a crystalline-to-amorphous phase transition in both the pristine and guest-adsorbed solids that led to a change in the fluorescence color (mechanofluorochromism) and a memory of the resulting color. Fluorescence drawings of five or more colors were created on glass or paper and could be readily erased by exposure to air and dichloromethane fumes. The structural and mechanistic aspects of the observations are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Normal and system lupus erythematosus red blood cell interactions studied by double trap optical tweezers: direct measurements of aggregation forces

    Science.gov (United States)

    Khokhlova, Maria D.; Lyubin, Eugeny V.; Zhdanov, Alexander G.; Rykova, Sophia Yu.; Sokolova, Irina A.; Fedyanin, Andrey A.

    2012-02-01

    Direct measurements of aggregation forces in piconewton range between two red blood cells in pair rouleau are performed under physiological conditions using double trap optical tweezers. Aggregation and disaggregation properties of healthy and pathologic (system lupus erythematosis) blood samples are analyzed. Strong difference in aggregation speed and behavior is revealed using the offered method which is proposed to be a promising tool for SLE monitoring at single cell level.

  11. 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.

  12. 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.

  13. Electron-correlated fragment-molecular-orbital calculations for biomolecular and nano systems.

    Science.gov (United States)

    Tanaka, Shigenori; Mochizuki, Yuji; Komeiji, Yuto; Okiyama, Yoshio; Fukuzawa, Kaori

    2014-06-14

    Recent developments in the fragment molecular orbital (FMO) method for theoretical formulation, implementation, and application to nano and biomolecular systems are reviewed. The FMO method has enabled ab initio quantum-mechanical calculations for large molecular systems such as protein-ligand complexes at a reasonable computational cost in a parallelized way. There have been a wealth of application outcomes from the FMO method in the fields of biochemistry, medicinal chemistry and nanotechnology, in which the electron correlation effects play vital roles. With the aid of the advances in high-performance computing, the FMO method promises larger, faster, and more accurate simulations of biomolecular and related systems, including the descriptions of dynamical behaviors in solvent environments. The current status and future prospects of the FMO scheme are addressed in these contexts.

  14. 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.

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

    Science.gov (United States)

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

    2010-11-05

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

  16. 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

  17. 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...

  18. 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...

  19. Probing the interaction forces of prostate cancer cells with collagen I and bone marrow derived stem cells on the single cell level.

    Directory of Open Access Journals (Sweden)

    Ediz Sariisik

    Full Text Available Adhesion of metastasizing prostate carcinoma cells was quantified for two carcinoma model cell lines LNCaP (lymph node-specific and PC3 (bone marrow-specific. By time-lapse microscopy and force spectroscopy we found PC3 cells to preferentially adhere to bone marrow-derived mesenchymal stem cells (SCP1 cell line. Using atomic force microscopy (AFM based force spectroscopy, the mechanical pattern of the adhesion to SCP1 cells was characterized for both prostate cancer cell lines and compared to a substrate consisting of pure collagen type I. PC3 cells dissipated more energy (27.6 aJ during the forced de-adhesion AFM experiments and showed significantly more adhesive and stronger bonds compared to LNCaP cells (20.1 aJ. The characteristic signatures of the detachment force traces revealed that, in contrast to the LNCaP cells, PC3 cells seem to utilize their filopodia in addition to establish adhesive bonds. Taken together, our study clearly demonstrates that PC3 cells have a superior adhesive affinity to bone marrow mesenchymal stem cells, compared to LNCaP. Semi-quantitative PCR on both prostate carcinoma cell lines revealed the expression of two Col-I binding integrin receptors, α1β1 and α2β1 in PC3 cells, suggesting their possible involvement in the specific interaction to the substrates. Further understanding of the exact mechanisms behind this phenomenon might lead to optimized therapeutic applications targeting the metastatic behavior of certain prostate cancer cells towards bone tissue.

  20. Combined particle-image velocimetry and force analysis of the three-dimensional fluid-structure interaction of a natural owl wing.

    Science.gov (United States)

    Winzen, A; Roidl, B; Schröder, W

    2016-04-01

    Low-speed aerodynamics has gained increasing interest due to its relevance for the design process of small flying air vehicles. These small aircraft operate at similar aerodynamic conditions as, e.g. birds which therefore can serve as role models of how to overcome the well-known problems of low Reynolds number flight. The flight of the barn owl is characterized by a very low flight velocity in conjunction with a low noise emission and a high level of maneuverability at stable flight conditions. To investigate the complex three-dimensional flow field and the corresponding local structural deformation in combination with their influence on the resulting aerodynamic forces, time-resolved stereoscopic particle-image velocimetry and force and moment measurements are performed on a prepared natural barn owl wing. Several spanwise positions are measured via PIV in a range of angles of attack [Formula: see text] 6° and Reynolds numbers 40 000 [Formula: see text] 120 000 based on the chord length. Additionally, the resulting forces and moments are recorded for -10° ≤ α ≤ 15° at the same Reynolds numbers. Depending on the spanwise position, the angle of attack, and the Reynolds number, the flow field on the wing's pressure side is characterized by either a region of flow separation, causing large-scale vortical structures which lead to a time-dependent deflection of the flexible wing structure or wing regions showing no instantaneous deflection but a reduction of the time-averaged mean wing curvature. Based on the force measurements the three-dimensional fluid-structure interaction is assumed to considerably impact the aerodynamic forces acting on the wing leading to a strong mechanical loading of the interface between the wing and body. These time-depending loads which result from the flexibility of the wing should be taken into consideration for the design of future small flying air vehicles using flexible wing structures.

  1. 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.

  2. View of the bacterial strains of Escherichia coli M-17 and its interaction with the nanoparticles of zinc oxide by means of atomic force microscopy

    International Nuclear Information System (INIS)

    Sagitova, A; Yaminsky, I; Meshkov, G

    2016-01-01

    Visualization of the structure of biological objects plays a key role in medicine, biotechnology, nanotechnology and IT-technology. Atomic force microscopy (AFM) is a promising method of studying of objects’ morphology and structure. In this work, AFM was used to determine the size and shape of the bacterial strains of Escherichia coli M-17 and visualization its interaction with the nanoparticles of zinc oxide. The suspension of E.coli bacteria was applied to natural mica and studied by contact mode using the FemtoScan multifunctional scanning probe microscope. (paper)

  3. Hybrid integral-differential simulator of EM force interactions/scenario-assessment tool with pre-computed influence matrix in applications to ITER

    Science.gov (United States)

    Rozov, V.; Alekseev, A.

    2015-08-01

    A necessity to address a wide spectrum of engineering problems in ITER determined the need for efficient tools for modeling of the magnetic environment and force interactions between the main components of the magnet system. The assessment of the operating window for the machine, determined by the electro-magnetic (EM) forces, and the check of feasibility of particular scenarios play an important role for ensuring the safety of exploitation. Such analysis-powered prevention of damages forms an element of the Machine Operations and Investment Protection strategy. The corresponding analysis is a necessary step in preparation of the commissioning, which finalizes the construction phase. It shall be supported by the development of the efficient and robust simulators and multi-physics/multi-system integration of models. The developed numerical model of interactions in the ITER magnetic system, based on the use of pre-computed influence matrices, facilitated immediate and complete assessment and systematic specification of EM loads on magnets in all foreseen operating regimes, their maximum values, envelopes and the most critical scenarios. The common principles of interaction in typical bilateral configurations have been generalized for asymmetry conditions, inspired by the plasma and by the hardware, including asymmetric plasma event and magnetic system fault cases. The specification of loads is supported by the technology of functional approximation of nodal and distributed data by continuous patterns/analytical interpolants. The global model of interactions together with the mesh-independent analytical format of output provides the source of self-consistent and transferable data on the spatial distribution of the system of forces for assessments of structural performance of the components, assemblies and supporting structures. The numerical model used is fully parametrized, which makes it very suitable for multi-variant and sensitivity studies (positioning, off

  4. View of the bacterial strains of Escherichia coli M-17 and its interaction with the nanoparticles of zinc oxide by means of atomic force microscopy

    Science.gov (United States)

    Sagitova, A.; Yaminsky, I.; Meshkov, G.

    2016-08-01

    Visualization of the structure of biological objects plays a key role in medicine, biotechnology, nanotechnology and IT-technology. Atomic force microscopy (AFM) is a promising method of studying of objects’ morphology and structure. In this work, AFM was used to determine the size and shape of the bacterial strains of Escherichia coli M-17 and visualization its interaction with the nanoparticles of zinc oxide. The suspension of E.coli bacteria was applied to natural mica and studied by contact mode using the FemtoScan multifunctional scanning probe microscope.

  5. Theoretical description of biomolecular hydration - Application to A-DNA

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, A.E.; Hummer, G. [Los Alamos National Laboratory, NM (United States); Soumpasis, D.M. [Max Planck Inst. for Biophysical Chemistry, Goettingen (Germany)

    1994-12-31

    The local density of water molecules around a biomolecule is constructed from calculated two- and three-points correlation functions of polar solvents in water using a Potential-of-Mean-Force (PMF) expansion. As a simple approximation, the hydration of all polar (including charged) groups in a biomolecule is represented by the hydration of water oxygen in bulk water, and the effect of non-polar groups on hydration are neglected, except for excluded volume effects. Pair and triplet correlation functions are calculated by molecular dynamics simulations. We present calculations of the structural hydration for ideal A-DNA molecules with sequences [d(CG){sub 5}]{sub 2} and [d(C{sub 5}G{sub 5})]{sub 2}. We find that this method can accurately reproduce the hydration patterns of A-DNA observed in neutron diffraction experiments on oriented DNA fibers.

  6. Theoretical description of biomolecular hydration - Application to A-DNA

    International Nuclear Information System (INIS)

    Garcia, A.E.; Hummer, G.; Soumpasis, D.M.

    1994-01-01

    The local density of water molecules around a biomolecule is constructed from calculated two- and three-points correlation functions of polar solvents in water using a Potential-of-Mean-Force (PMF) expansion. As a simple approximation, the hydration of all polar (including charged) groups in a biomolecule is represented by the hydration of water oxygen in bulk water, and the effect of non-polar groups on hydration are neglected, except for excluded volume effects. Pair and triplet correlation functions are calculated by molecular dynamics simulations. We present calculations of the structural hydration for ideal A-DNA molecules with sequences [d(CG) 5 ] 2 and [d(C 5 G 5 )] 2 . We find that this method can accurately reproduce the hydration patterns of A-DNA observed in neutron diffraction experiments on oriented DNA fibers

  7. 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.

  8. 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.

  9. Preliminary Assessment of Potential Avian Interactions at Four Proposed Wind Energy Facilities on Vandenberg Air Force Base, California

    Energy Technology Data Exchange (ETDEWEB)

    2004-08-01

    The United States Air Force (USAF) is investigating whether to install wind turbines to provide a supplemental source of electricity at Vandenberg Air Force Base (VAFB) near Lompoc, California. As part of that investigation, VAFB sought assistance from the U.S. Department of Energy's National Renewable Energy Laboratory (NREL) to provide a preliminary characterization of the potential risk to wildlife resources (mainly birds and bats) from wind turbine installations. With wind power development expanding throughout North America and Europe, concerns have surfaced over the number of bird fatalities associated with wind turbines. Guidelines developed for the wind industry by the National Wind Coordinating Committee (NWCC) recommend assessing potential impacts to birds, bats, and other potentially sensitive resources before construction. The primary purpose of an assessment is to identify potential conflicts with sensitive resources, to assist developers with identifying their permitting needs, and to develop strategies to avoid impacts or to mitigate their effects. This report provides a preliminary (Phase I) biological assessment of potential impacts to birds and bats that might result from construction and operation of the proposed wind energy facilities on VAFB.

  10. Unveiling aerosol-cloud interactions - Part 1: Cloud contamination in satellite products enhances the aerosol indirect forcing estimate

    Science.gov (United States)

    Christensen, Matthew W.; Neubauer, David; Poulsen, Caroline A.; Thomas, Gareth E.; McGarragh, Gregory R.; Povey, Adam C.; Proud, Simon R.; Grainger, Roy G.

    2017-11-01

    Increased concentrations of aerosol can enhance the albedo of warm low-level cloud. Accurately quantifying this relationship from space is challenging due in part to contamination of aerosol statistics near clouds. Aerosol retrievals near clouds can be influenced by stray cloud particles in areas assumed to be cloud-free, particle swelling by humidification, shadows and enhanced scattering into the aerosol field from (3-D radiative transfer) clouds. To screen for this contamination we have developed a new cloud-aerosol pairing algorithm (CAPA) to link cloud observations to the nearest aerosol retrieval within the satellite image. The distance between each aerosol retrieval and nearest cloud is also computed in CAPA. Results from two independent satellite imagers, the Advanced Along-Track Scanning Radiometer (AATSR) and Moderate Resolution Imaging Spectroradiometer (MODIS), show a marked reduction in the strength of the intrinsic aerosol indirect radiative forcing when selecting aerosol pairs that are located farther away from the clouds (-0.28±0.26 W m-2) compared to those including pairs that are within 15 km of the nearest cloud (-0.49±0.18 W m-2). The larger aerosol optical depths in closer proximity to cloud artificially enhance the relationship between aerosol-loading, cloud albedo, and cloud fraction. These results suggest that previous satellite-based radiative forcing estimates represented in key climate reports may be exaggerated due to the inclusion of retrieval artefacts in the aerosol located near clouds.

  11. Moral Emotions during Military Deployments of Dutch Forces: A Qualitative Study on Moral Emotions in Intercultural Interactions

    NARCIS (Netherlands)

    Schut, M; de Graaff, Miriam; Verweij, D.E.M.

    2015-01-01

    Which emotions are generated by the behavior of “the other” in intercultural interactions that Dutch soldiers perceive as conflicting with their own values? How are these emotions related to types of behavioral reactions of Dutch military personnel? This preliminary study explores the emotional and

  12. Polymer-surfactant interactions studied by titration microcalorimetry : Influence of polymer hydrophobicity, electrostatic forces, and surfactant aggregational state

    NARCIS (Netherlands)

    Kevelam, J; van Breemen, J.F.L.; Blokzijl, W.; Engberts, J.B.F.N.

    1996-01-01

    Isothermal titration microcalorimetry has been applied to investigate the interactions between hydrophobically-modified water-soluble polymers and surfactants. The following polymers were used in this study: poly(sodium acrylate-co-n-alkyl methacrylate) (A), where n-alkyl = C9H19, C12H25, and C18H37

  13. AFM force spectroscopy reveals how subtle structural differences affect the interaction strength between Candida albicans and DC-SIGN

    NARCIS (Netherlands)

    Riet, J. te; Reinieren-Beeren, I.M.J.; Figdor, C.G.; Cambi, A.

    2015-01-01

    The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, such as the C-type lectin dendritic cell-specific intracellular cell adhesion molecule-3 (ICAM-3)-grabbing

  14. The driving forces of stability. Exploring the nature of long-term bureaucracy-interest group interactions

    NARCIS (Netherlands)

    Braun, C.H.J.M.

    2013-01-01

    This article explores the nature of long-term interactions between bureaucrats and interest groups by examining two behavioral logics associated with stability in public policy making. In addition to the implicit short-term strategic choices that usually feature in resource-exchange explanations of

  15. Analysis of the Usage of Magnetic Force-directed Approach and Visual Techniques for Interactive Context-based Drawing of Multi-attributed Graphs

    Directory of Open Access Journals (Sweden)

    Zabiniako Vitaly

    2014-12-01

    Full Text Available In this article, the authors perform an analysis in order to assess adaptation of magnetic force-directed algorithms for context-based information extraction from multi-attributed graphs during visualization sessions. Theoretic standings behind magnetic force-directed approach are stated together with review on how particular features of respective algorithms in combination with appropriate visual techniques are especially suitable for improved processing and presenting of knowledge that is captured in form of graphs. The complexity of retrieving multi-attributed information within the proposed approach is handled with dedicated tools, such as selective attraction of nodes to MFE (Magnetic Force Emitter based on search criteria, localization of POI (Point of Interest regions, graph node anchoring, etc. Implicit compatibility of aforementioned tools with interactive nature of data exploration is distinguished. Description of case study, based on bibliometric network analysis is given, which is followed by the review of existing related works in this field. Conclusions are made and further studies in the field of visualization of multi-attributed graphs are defined.

  16. Automation of the CHARMM General Force Field (CGenFF) I: bond perception and atom typing.

    Science.gov (United States)

    Vanommeslaeghe, K; MacKerell, A D

    2012-12-21

    Molecular mechanics force fields are widely used in computer-aided drug design for the study of drug-like molecules alone or interacting with biological systems. In simulations involving biological macromolecules, the biological part is typically represented by a specialized biomolecular force field, while the drug is represented by a matching general (organic) force field. In order to apply these general force fields to an arbitrary drug-like molecule, functionality for assignment of atom types, parameters, and charges is required. In the present article, which is part I of a series of two, we present the algorithms for bond perception and atom typing for the CHARMM General Force Field (CGenFF). The CGenFF atom typer first associates attributes to the atoms and bonds in a molecule, such as valence, bond order, and ring membership among others. Of note are a number of features that are specifically required for CGenFF. This information is then used by the atom typing routine to assign CGenFF atom types based on a programmable decision tree. This allows for straightforward implementation of CGenFF's complicated atom typing rules and for equally straightforward updating of the atom typing scheme as the force field grows. The presented atom typer was validated by assigning correct atom types on 477 model compounds including in the training set as well as 126 test-set molecules that were constructed to specifically verify its different components. The program may be utilized via an online implementation at https://www.paramchem.org/ .

  17. 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.

  18. A Moessbauer study on the interaction between biomolecular lipid membranes and ferric ferrous ions

    International Nuclear Information System (INIS)

    Karvaly, B.; Badinka, C.; Keszthelyi, L.; Erdei, L.

    1975-01-01

    The results of Moessbauer experiments made on liposome systems of a large specific area are presented. In the study lecithin was used as a membrane-forming material. The measurements were carried out on frozen liposome systems, at various 57 Fe/lipid concentration ratios, pH values and temperatures. Since the presence of liposomes had no noticeable influence on the Moessbauer spectra of Fe 2+ ions, only lecithin Fe 3+ systems were considered. Moessbauer spectra in case of Fe 3+ solutions with lecithin showed marked quadrupole splitting (exhibiting an anomalous temperature dependence) which is not shown in case of pure Fe 3+ solution. (Z.S.)

  19. Investigation on biomolecular interactions of nickel(II) complexes with monoanionic bidentate ligands

    Science.gov (United States)

    Jayamani, Arumugam; Sethupathi, Murugan; Ojwach, Stephen O.; Sengottuvelan, Nallathambi

    2018-01-01

    Reactions of monoanionic bidentate ligands 5-methylsalicylaldehyde (5-msal), 5-bromosalicylaldehyde (5-brsal), 5-nitrosalicylaldehyde (5-nsal) and 2-hydroxy-1-naphthaldehyde (2-hnap) with nickel perchlorate hexahydrate produced nickel(II) complexes 1-4, respectively. Single crystal X-ray analyses of complexes 1 and 2 confirmed bidentate mode of the ligands with O˄O coordination to give square planar geometry around nickel atoms. Complexes 1-4 showed one quasi-reversible redox peak at cathodic region (-0.67 to -0.80 V) and one redox peak at anodic region (+1.08 to +1.44 V) assignable to the Ni(II)/Ni(I) and Ni(II)/Ni(III) redox couples, respectively. The complexes exhibited good bovine serum albumin (BSA) binding abilities with a maximum binding constant of 1.96 × 105 M-1. The binding of complexes with calf thymus DNA (ctDNA) showed that the binding affinity is consistent with an increase in steric bulk of the ligands. The nuclease activity of the complexes showed efficient oxidative cleavage in the presence of hydrogen peroxide as an oxidizing agent. The complexes showed higher zone of inhibition when screened for antimicrobial activity against bacteria and human pathogenic fungi.

  20. Biomolecular interactions and responses of human epithelial and macrophage cells to engineered nanomaterials.

    Energy Technology Data Exchange (ETDEWEB)

    Kotula, Paul Gabriel; Brozik, Susan Marie; Achyuthan, Komandoor E.; Greene, Adrienne Celeste; Timlin, Jerilyn Ann; Bachand, George David; Bachand, Marlene; Aaron, Jesse S.; Allen, Amy; Seagrave, Jean-Clare

    2011-12-01

    Engineered nanomaterials (ENMs) are increasingly being used in commercial products, particularly in the biomedical, cosmetic, and clothing industries. For example, pants and shirts are routinely manufactured with silver nanoparticles to render them 'wrinkle-free.' Despite the growing applications, the associated environmental health and safety (EHS) impacts are completely unknown. The significance of this problem became pervasive within the general public when Prince Charles authored an article in 2004 warning of the potential social, ethical, health, and environmental issues connected to nanotechnology. The EHS concerns, however, continued to receive relatively little consideration from federal agencies as compared with large investments in basic nanoscience R&D. The mounting literature regarding the toxicology of ENMs (e.g., the ability of inhaled nanoparticles to cross the blood-brain barrier; Kwon et al., 2008, J. Occup. Health 50, 1) has spurred a recent realization within the NNI and other federal agencies that the EHS impacts related to nanotechnology must be addressed now. In our study we proposed to address critical aspects of this problem by developing primary correlations between nanoparticle properties and their effects on cell health and toxicity. A critical challenge embodied within this problem arises from the ability to synthesize nanoparticles with a wide array of physical properties (e.g., size, shape, composition, surface chemistry, etc.), which in turn creates an immense, multidimensional problem in assessing toxicological effects. In this work we first investigated varying sizes of quantum dots (Qdots) and their ability to cross cell membranes based on their aspect ratio utilizing hyperspectral confocal fluorescence microscopy. We then studied toxicity of epithelial cell lines that were exposed to different sized gold and silver nanoparticles using advanced imaging techniques, biochemical analyses, and optical and mass spectrometry methods. Finally we evaluated a new assay to measure transglutaminase (TG) activity; a potential marker for cell toxicity.

  1. Cell-matrix interactions of Entamoeba histolytica and E. dispar. A comparative study by electron-, atomic force- and confocal microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Talamás-Lara, Daniel, E-mail: daniel_talamas@hotmail.com [Department of Infectomics and Molecular Pathogenesis, Centro de Investigación y de Estudios Avanzados, Apartado Postal 14-740, Mexico City (Mexico); Talamás-Rohana, Patricia, E-mail: ptr@cinvestav.mx [Department of Infectomics and Molecular Pathogenesis, Centro de Investigación y de Estudios Avanzados, Apartado Postal 14-740, Mexico City (Mexico); Fragoso-Soriano, Rogelio Jaime, E-mail: rogelio@fis.cinvestav.mx [Department of Physics, Centro de Investigación y de Estudios Avanzados, Apartado Postal 14-740, Mexico City (Mexico); Espinosa-Cantellano, Martha, E-mail: mespinosac@cinvestav.mx [Department of Infectomics and Molecular Pathogenesis, Centro de Investigación y de Estudios Avanzados, Apartado Postal 14-740, Mexico City (Mexico); Chávez-Munguía, Bibiana, E-mail: bchavez@cinvestav.mx [Department of Infectomics and Molecular Pathogenesis, Centro de Investigación y de Estudios Avanzados, Apartado Postal 14-740, Mexico City (Mexico); González-Robles, Arturo, E-mail: goroa@cinvestav.mx [Department of Infectomics and Molecular Pathogenesis, Centro de Investigación y de Estudios Avanzados, Apartado Postal 14-740, Mexico City (Mexico); Martínez-Palomo, Adolfo, E-mail: amartine@cinvestav.mx [Department of Infectomics and Molecular Pathogenesis, Centro de Investigación y de Estudios Avanzados, Apartado Postal 14-740, Mexico City (Mexico)

    2015-10-01

    Invasion of tissues by Entamoeba histolytica is a multistep process that initiates with the adhesion of the parasite to target tissues. The recognition of the non-invasive Entamoeba dispar as a distinct, but closely related protozoan species raised the question as to whether the lack of its pathogenic potential could be related to a weaker adhesion due to limited cytoskeleton restructuring capacity. We here compared the adhesion process of both amebas to fibronectin through scanning, transmission, atomic force, and confocal microscopy. In addition, electrophoretic and western blot assays of actin were also compared. Adhesion of E. histolytica to fibronectin involves a dramatic reorganization of the actin network that results in a tighter contact to and the subsequent focal degradation of the fibronectin matrix. In contrast, E. dispar showed no regions of focal adhesion, the cytoskeleton was poorly reorganized and there was little fibronectin degradation. In addition, atomic force microscopy using topographic, error signal and phase modes revealed clear-cut differences at the site of contact of both amebas with the substrate. In spite of the morphological and genetic similarities between E. histolytica and E. dispar the present results demonstrate striking differences in their respective cell-to-matrix adhesion processes, which may be of relevance for understanding the invasive character of E. histolytica. - Highlights: • Striking differences in adhesion to FN between E. histolytica and E. dispar. • A greater degree of cell stiffness in E. histolytica with respect to E. dispar. • E. histolytica but not E. dispar forms regions of close contact with FN. • The actin cytoskeleton is involved in the pathogenicity of E. histolytica.

  2. Cell-matrix interactions of Entamoeba histolytica and E. dispar. A comparative study by electron-, atomic force- and confocal microscopy

    International Nuclear Information System (INIS)

    Talamás-Lara, Daniel; Talamás-Rohana, Patricia; Fragoso-Soriano, Rogelio Jaime; Espinosa-Cantellano, Martha; Chávez-Munguía, Bibiana; González-Robles, Arturo; Martínez-Palomo, Adolfo

    2015-01-01

    Invasion of tissues by Entamoeba histolytica is a multistep process that initiates with the adhesion of the parasite to target tissues. The recognition of the non-invasive Entamoeba dispar as a distinct, but closely related protozoan species raised the question as to whether the lack of its pathogenic potential could be related to a weaker adhesion due to limited cytoskeleton restructuring capacity. We here compared the adhesion process of both amebas to fibronectin through scanning, transmission, atomic force, and confocal microscopy. In addition, electrophoretic and western blot assays of actin were also compared. Adhesion of E. histolytica to fibronectin involves a dramatic reorganization of the actin network that results in a tighter contact to and the subsequent focal degradation of the fibronectin matrix. In contrast, E. dispar showed no regions of focal adhesion, the cytoskeleton was poorly reorganized and there was little fibronectin degradation. In addition, atomic force microscopy using topographic, error signal and phase modes revealed clear-cut differences at the site of contact of both amebas with the substrate. In spite of the morphological and genetic similarities between E. histolytica and E. dispar the present results demonstrate striking differences in their respective cell-to-matrix adhesion processes, which may be of relevance for understanding the invasive character of E. histolytica. - Highlights: • Striking differences in adhesion to FN between E. histolytica and E. dispar. • A greater degree of cell stiffness in E. histolytica with respect to E. dispar. • E. histolytica but not E. dispar forms regions of close contact with FN. • The actin cytoskeleton is involved in the pathogenicity of E. histolytica

  3. Characterization of the interaction forces in a drug carrier complex of doxorubicin with a drug-binding peptide.

    Science.gov (United States)

    Gocheva, Gergana; Ilieva, Nina; Peneva, Kalina; Ivanova, Anela

    2018-04-01

    Polypeptide-based materials are used as building blocks for drug delivery systems aimed at toxicity decrease in chemotherapeutics. A molecular-level approach is adopted for investigating the non-covalent interactions between doxorubicin and a recently synthesized drug-binging peptide as a key part of a system for delivery to neoplastic cells. Molecular dynamics simulations in aqueous solution at room and body temperature are applied to investigate the structure and the binding modes within the drug-peptide complex. The tryptophans are outlined as the main chemotherapeutic adsorption sites, and the importance of their placement in the peptide sequence is highlighted. The drug-peptide binging energy is evaluated by density functional theory calculations. Principal component analysis reveals comparable importance of several types of interaction for the binding strength. π-Stacking is dominant, but other factors are also significant: intercalation, peptide backbone stacking, electrostatics, dispersion, and solvation. Intra- and intermolecular H-bonding also stabilizes the complexes. The influence of solvent molecules on the binding energy is mild. The obtained data characterize the drug-to-peptide attachment as a mainly attractive collective process with interactions spanning a broad range of values. These results explain with atomistic detail the experimentally registered doxorubicin-binging ability of the peptide and outline the complex as a prospective carrying unit that can be employed in design of drug delivery systems. © 2017 John Wiley & Sons A/S.

  4. Biomolecular-solvent stereodynamic coupling probed by deuteration

    International Nuclear Information System (INIS)

    Fornili, S.L.; Leone, M.; Madonia, F.; Migliore, M.; Palma-Vittorelli, M.B.; Palma, M.U.; San Biagio, P.L.

    1983-01-01

    Thermodynamic interpretation of experiments with isotopically perturbed solvent supports the view that solvent stereodynamics is directly relevant to thermodynamic stability of biomolecules. According with the current understanding of the structure of the aqueous solvent, in any stereodynamic configuration of the latter, connectivity pathways are identifiable for their topologic and order properties. Perturbing the solvent by isotopic substitution or, e.g., by addition of co-solvents, can therefore be viewed as reinforcing or otherwise perturbing these topologic structures. This microscopic model readily visualizes thermodynamic interpretation. In conclusion, the topologic stereodynamic structures of connectivity pathways in the solvent, as modified by interaction with solutes, acquire a specific thermodynamic and biological significance, and the problem of thermodynamic and functional stability of biomolecules is seen in its full pertinent phase space

  5. Perspectives for quantum interference with biomolecules and biomolecular clusters

    International Nuclear Information System (INIS)

    Geyer, P; Sezer, U; Rodewald, J; Mairhofer, L; Dörre, N; Haslinger, P; Eibenberger, S; Brand, C; Arndt, M

    2016-01-01

    Modern quantum optics encompasses a wide field of phenomena that are either related to the discrete quantum nature of light, the quantum wave nature of matter or light–matter interactions. We here discuss new perspectives for quantum optics with biological nanoparticles. We focus in particular on the prospects of matter-wave interferometry with amino acids, nucleotides, polypeptides or DNA strands. We motivate the challenge of preparing these objects in a ‘biomimetic’ environment and argue that hydrated molecular beam sources are promising tools for quantum-assisted metrology. The method exploits the high sensitivity of matter-wave interference fringes to dephasing and shifts in the presence of external perturbations to access and determine molecular properties. (invited comment)

  6. Combining an Elastic Network With a Coarse-Grained Molecular Force Field : Structure, Dynamics, and Intermolecular Recognition

    NARCIS (Netherlands)

    Periole, Xavier; Cavalli, Marco; Marrink, Siewert-Jan; Ceruso, Marco A.

    Structure-based and physics-based coarse-grained molecular force fields have become attractive approaches to gain mechanistic insight into the function of large biomolecular assemblies. Here, we study how both approaches can be combined into a single representation, that we term ELNEDIN. In this

  7. Interfacial force measurements using atomic force microscopy

    NARCIS (Netherlands)

    Chu, L.

    2018-01-01

    Atomic Force Microscopy (AFM) can not only image the topography of surfaces at atomic resolution, but can also measure accurately the different interaction forces, like repulsive, adhesive and lateral existing between an AFM tip and the sample surface. Based on AFM, various extended techniques have

  8. 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

  9. 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

  10. Considering space weather forces interaction on human health: the equilibrium paradigm in clinical cosmobiology - is it equal?

    Science.gov (United States)

    Stoupel, Eliyahu

    2015-03-01

    We are constantly affected by changes in space weather. The principal "players" are solar activity (SA), geomagnetic activity (GMA) and antagonistic to them, cosmic ray activity (CRA) and high energy proton flux. CRA is measured by neutron activity on the earth's surface in imp/min. SA and GMA are linked and serve as a shield for the earth from CRA. For a long time SA and GMA were the main areas of studies. The aim of this study was to compare some effects of the mentioned forces and discuss the temporal distribution of both groups of space weather, in relation to their effects on humans. The time distribution of GMA storms (daily) was compared with quiet (low) GMA, with higher CRA (neutron activity). Space weather data were obtained from the USA, Russia and Finland. A total of 4383 days were analyzed in the years 2000-2012. A total of 71 days (1.62%) of geomagnetic storms (GS) and 2753 days (63.8%) of quiet (I0) GMA were registered. A second study was provided including the years 1983-2007 (9131 days); here 3800 days (41.62%) were quiet GMA days and 400 storm days (4.38%). According to publications in the medical literature, many phenomena are connected with the extremes of space weather. Despite a great number of publications and the significant role of GS, it is a relatively rare event and most medical emergencies and deaths occur on days of low GMA, accompanied by higher CRA (neutron activity). High neutron activity deserves more attention when analyzing space effects on human health and their mechanism of action.

  11. Individual differences in the forced swimming test and the effect of environmental enrichment: searching for an interaction.

    Science.gov (United States)

    Sequeira-Cordero, A; Mora-Gallegos, A; Cuenca-Berger, P; Fornaguera-Trías, J

    2014-04-18

    Animals with low and high immobility in the forced swimming test (FST) differ in a number of neurobehavioral factors. A growing body of evidence suggests that the exposure to enriched environments mediates a number of changes in the brain. Therefore, we studied if animals' individuality can somehow modulate the response to environmental stimuli. Male rats were classified according to their immobility time scores in the FST test session as animals with low, medium or high immobility. Then, rats from groups with low and high immobility were randomly distributed in two groups to be reared in different housing conditions (i.e., enriched and standard conditions) during 8weeks. Animals were subjected to the open field test (OFT) before and 6weeks after the start of housing protocol. Rats with high immobility in the FST also showed high ambulation and high rearing time in the first OFT. Such findings were not observed in the second OFT. Conversely, an effect of environmental enrichment was found in the second OFT where enriched animals showed lower ambulation and higher grooming time than the standard control group. Rats were sacrificed after the housing protocol and neurochemical content and/or gene expression were studied in three different brain regions: the prefrontal cortex, the hippocampus and the nucleus accumbens. Rats with low immobility showed significantly higher accumbal 5-HT levels than animals with high immobility, whereas no neurochemical differences were observed between enriched and standard animals. Regarding expression data, however, an effect of enrichment on accumbal corticotropin-releasing factor (CRF) and its receptor 1 (CRFR1) levels was observed, and such effect depended on immobility levels. Thus, our results not only allowed us to identify a number of differences between animals with low and high immobility or animals housed in standard and enriched conditions, but also suggested that animals' individuality modulated in some way the response to

  12. On Interactions of Oscillation Modes for a Weakly Non-Linear Undamped Elastic Beam with AN External Force

    Science.gov (United States)

    BOERTJENS, G. J.; VAN HORSSEN, W. T.

    2000-08-01

    In this paper an initial-boundary value problem for the vertical displacement of a weakly non-linear elastic beam with an harmonic excitation in the horizontal direction at the ends of the beam is studied. The initial-boundary value problem can be regarded as a simple model describing oscillations of flexible structures like suspension bridges or iced overhead transmission lines. Using a two-time-scales perturbation method an approximation of the solution of the initial-boundary value problem is constructed. Interactions between different oscillation modes of the beam are studied. It is shown that for certain external excitations, depending on the phase of an oscillation mode, the amplitude of specific oscillation modes changes.

  13. 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.

  14. 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

  15. Explicit polarization: a quantum mechanical framework for developing next generation force fields.

    Science.gov (United States)

    Gao, Jiali; Truhlar, Donald G; Wang, Yingjie; Mazack, Michael J M; Löffler, Patrick; Provorse, Makenzie R; Rehak, Pavel

    2014-09-16

    Conspectus Molecular mechanical force fields have been successfully used to model condensed-phase and biological systems for a half century. By means of careful parametrization, such classical force fields can be used to provide useful interpretations of experimental findings and predictions of certain properties. Yet, there is a need to further improve computational accuracy for the quantitative prediction of biomolecular interactions and to model properties that depend on the wave functions and not just the energy terms. A new strategy called explicit polarization (X-Pol) has been developed to construct the potential energy surface and wave functions for macromolecular and liquid-phase simulations on the basis of quantum mechanics rather than only using quantum mechanical results to fit analytic force fields. In this spirit, this approach is called a quantum mechanical force field (QMFF). X-Pol is a general fragment method for electronic structure calculations based on the partition of a condensed-phase or macromolecular system into subsystems ("fragments") to achieve computational efficiency. Here, intrafragment energy and the mutual electronic polarization of interfragment interactions are treated explicitly using quantum mechanics. X-Pol can be used as a general, multilevel electronic structure model for macromolecular systems, and it can also serve as a new-generation force field. As a quantum chemical model, a variational many-body (VMB) expansion approach is used to systematically improve interfragment interactions, including exchange repulsion, charge delocalization, dispersion, and other correlation energies. As a quantum mechanical force field, these energy terms are approximated by empirical functions in the spirit of conventional molecular mechanics. This Account first reviews the formulation of X-Pol, in the full variationally correct version, in the faster embedded version, and with systematic many-body improvements. We discuss illustrative examples

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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...

  1. Interactions of Histone Acetyltransferase p300 with the Nuclear Proteins Histone and HMGB1, As Revealed by Single Molecule Atomic Force Spectroscopy.

    Science.gov (United States)

    Banerjee, S; Rakshit, T; Sett, S; Mukhopadhyay, R

    2015-10-22

    One of the important properties of the transcriptional coactivator p300 is histone acetyltransferase (HAT) activity that enables p300 to influence chromatin action via histone modulation. p300 can exert its HAT action upon the other nuclear proteins too--one notable example being the transcription-factor-like protein HMGB1, which functions also as a cytokine, and whose accumulation in the cytoplasm, as a response to tissue damage, is triggered by its acetylation. Hitherto, no information on the structure and stability of the complexes between full-length p300 (p300FL) (300 kDa) and the histone/HMGB1 proteins are available, probably due to the presence of unstructured regions within p300FL that makes it difficult to be crystallized. Herein, we have adopted the high-resolution atomic force microscopy (AFM) approach, which allows molecularly resolved three-dimensional contour mapping of a protein molecule of any size and structure. From the off-rate and activation barrier values, obtained using single molecule dynamic force spectroscopy, the biochemical proposition of preferential binding of p300FL to histone H3, compared to the octameric histone, can be validated. Importantly, from the energy landscape of the dissociation events, a model for the p300-histone and the p300-HMGB1 dynamic complexes that HAT forms, can be proposed. The lower unbinding forces of the complexes observed in acetylating conditions, compared to those observed in non-acetylating conditions, indicate that upon acetylation, p300 tends to weakly associate, probably as an outcome of charge alterations on the histone/HMGB1 surface and/or acetylation-induced conformational changes. To our knowledge, for the first time, a single molecule level treatment of the interactions of HAT, where the full-length protein is considered, is being reported.

  2. A micromachined membrane-based active probe for biomolecular mechanics measurement

    Science.gov (United States)

    Torun, H.; Sutanto, J.; Sarangapani, K. K.; Joseph, P.; Degertekin, F. L.; Zhu, C.

    2007-04-01

    A novel micromachined, membrane-based probe has been developed and fabricated as assays to enable parallel measurements. Each probe in the array can be individually actuated, and the membrane displacement can be measured with high resolution using an integrated diffraction-based optical interferometer. To illustrate its application in single-molecule mechanics experiments, this membrane probe was used to measure unbinding forces between L-selectin reconstituted in a polymer-cushioned lipid bilayer on the probe membrane and an antibody adsorbed on an atomic force microscope cantilever. Piconewton range forces between single pairs of interacting molecules were measured from the cantilever bending while using the membrane probe as an actuator. The integrated diffraction-based optical interferometer of the probe was demonstrated to have floor for frequencies as low as 3 Hz with a differential readout scheme. With soft probe membranes, this low noise level would be suitable for direct force measurements without the need for a cantilever. Furthermore, the probe membranes were shown to have 0.5 µm actuation range with a flat response up to 100 kHz, enabling measurements at fast speeds.

  3. Antidepressant-like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with fluoxetine [correction of flouxetine].

    Science.gov (United States)

    Vázquez-Palacios, G; Bonilla-Jaime, H; Velázquez-Moctezuma, J

    2004-05-01

    An antidepressant action of nicotine (NIC) has recently been suggested. Flouxetine, a selective serotonin reuptake inhibitor, is currently the most widely used antidepressant. In the present study, we analyzed the effects of the administration of NIC, fluoxetine (FLX), and the combination of both drugs given acutely, subchronically, and chronically as well as 7 days after chronic administration of these drugs on the forced swim test. Results showed that NIC induced a significant reduction of the time in immobility during the forced swim test (antidepressant effect), with a concomitant increase in swimming activity (serotonergic activation), after acute administration. These effects remain the same after subchronic and chronic administration. FLX failed to induce any effect after acute administration but did induce a significant decrease of immobility and an increase of swimming after subchronic administration. The effect of the chronic administration was significantly larger compared to subchronic administration. The combination of both drugs induced a larger effect than that observed after a single administration but only after subchronic treatment. No effect was observed after the end of the 7-day treatments. Data suggest that NIC has an antidepressant action that is expressed faster than FLX but remains the same later. Thus, cholinergic-serotonergic interactions could play an important role in the treatment of depression.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-15

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

  5. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions ...

  6. Electro-optic deflectors deliver advantages over acousto-optical deflectors in a high resolution, ultra-fast force-clamp optical trap.

    Science.gov (United States)

    Woody, Michael S; Capitanio, Marco; Ostap, E Michael; Goldman, Yale E

    2018-04-30

    We characterized experimental artifacts arising from the non-linear response of acousto-optical deflectors (AODs) in an ultra-fast force-clamp optical trap and have shown that using electro-optical deflectors (EODs) instead eliminates these artifacts. We give an example of the effects of these artifacts in our ultra-fast force clamp studies of the interaction of myosin with actin filaments. The experimental setup, based on the concept of Capitanio et al. [Nat. Methods 9, 1013-1019 (2012)] utilizes a bead-actin-bead dumbbell held in two force-clamped optical traps which apply a load to the dumbbell to move it at a constant velocity. When myosin binds to actin, the filament motion stops quickly as the total force from the optical traps is transferred to the actomyosin attachment. We found that in our setup, AODs were unsuitable for beam steering due to non-linear variations in beam intensity and deflection angle as a function of driving frequency, likely caused by low-amplitude standing acoustic waves in the deflectors. These aberrations caused instability in the force feedback loops leading to artifactual jumps in the trap position. We demonstrate that beam steering with EODs improves the performance of our instrument. Combining the superior beam-steering capability of the EODs, force acquisition via back-focal-plane interferometry, and dual high-speed FPGA-based feedback loops, we apply precise and constant loads to study the dynamics of interactions between actin and myosin. The same concept applies to studies of other biomolecular interactions.

  7. Numerical Simulations of Turbulent Molecular Clouds Regulated by Radiation Feedback Forces. II. Radiation-Gas Interactions and Outflows

    Science.gov (United States)

    Raskutti, Sudhir; Ostriker, Eve C.; Skinner, M. Aaron

    2017-12-01

    Momentum deposition by radiation pressure from young, massive stars may help to destroy molecular clouds and unbind stellar clusters by driving large-scale outflows. We extend our previous numerical radiation hydrodynamic study of turbulent star-forming clouds to analyze the detailed interaction between non-ionizing UV radiation and the cloud material. Our simulations trace the evolution of gas and star particles through self-gravitating collapse, star formation, and cloud destruction via radiation-driven outflows. These models are idealized in that we include only radiation feedback and adopt an isothermal equation of state. Turbulence creates a structure of dense filaments and large holes through which radiation escapes, such that only ˜50% of the radiation is (cumulatively) absorbed by the end of star formation. The surface density distribution of gas by mass as seen by the central cluster is roughly lognormal with {σ }{ln{{Σ }}}=1.3{--}1.7, similar to the externally projected surface density distribution. This allows low surface density regions to be driven outwards to nearly 10 times their initial escape speed {v}{esc}. Although the velocity distribution of outflows is broadened by the lognormal surface density distribution, the overall efficiency of momentum injection to the gas cloud is reduced because much of the radiation escapes. The mean outflow velocity is approximately twice the escape speed from the initial cloud radius. Our results are also informative for understanding galactic-scale wind driving by radiation, in particular, the relationship between velocity and surface density for individual outflow structures and the resulting velocity and mass distributions arising from turbulent sources.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.