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

Energy Technology Data Exchange (ETDEWEB)

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

1994-12-01

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

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.

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.

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.

Biomolecular structure refinement using the GROMOS simulation software

International Nuclear Information System (INIS)

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

2011-01-01

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

Biomolecular structure refinement using the GROMOS simulation software

Energy Technology Data Exchange (ETDEWEB)

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

2011-11-15

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

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.

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

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.

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

National Research Council Canada - National Science Library

Frazier, John; Chusak, Yaroslav; Foy, Brent

2008-01-01

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

A statistical nanomechanism of biomolecular patterning actuated by surface potential

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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.

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…

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.

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.

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.

Biomolecular condensates: organizers of cellular biochemistry.

Science.gov (United States)

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

2017-05-01

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

Programming in biomolecular computation

DEFF Research Database (Denmark)

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

2011-01-01

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

Smartphones for cell and biomolecular detection.

Science.gov (United States)

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

2014-11-01

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

Biomolecular 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.

An Overview of Biomolecular Event Extraction from Scientific Documents.

Science.gov (United States)

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

2015-01-01

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

An Overview of Biomolecular Event Extraction from Scientific Documents

Directory of Open Access Journals (Sweden)

Jorge A. Vanegas

2015-01-01

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

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

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.

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

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.

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.

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.

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.

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

restricted location of the enzyme's active site and that the geranylgeranyl diphosphate derived pyrophosphate moiety remains in the ACS active site thereby directing the cyclization process. Our cumulative data confirm that amino acids constituting the G-loop of diterpene synthases are involved in the open to the closed, catalytically active enzyme conformation. This study demonstrates that a simple and rapid biomolecular modeling procedure can predict catalytically relevant amino acids. The approach reduces computational and experimental screening efforts for diterpene synthase structure-function analyses.

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

the enzyme's active site and that the geranylgeranyl diphosphate derived pyrophosphate moiety remains in the ACS active site thereby directing the cyclization process. Our cumulative data confirm that amino acids constituting the G-loop of diterpene synthases are involved in the open to the closed, catalytically active enzyme conformation. This study demonstrates that a simple and rapid biomolecular modeling procedure can predict catalytically relevant amino acids. The approach reduces computational and experimental screening efforts for diterpene synthase structure-function analyses.

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

of the enzyme’s active site and that the geranylgeranyl diphosphate derived pyrophosphate moiety remains in the ACS active site thereby directing the cyclization process. Our cumulative data confirm that amino acids constituting the G-loop of diterpene synthases are involved in the open to the closed, catalytically active enzyme conformation. This study demonstrates that a simple and rapid biomolecular modelling procedure can predict catalytically relevant amino acids. The approach reduces computational and experimental screening efforts for diterpene synthase structure-function analyses.

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.

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

MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations.

Science.gov (United States)

Vergara-Perez, Sandra; Marucho, Marcelo

2016-01-01

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

MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations

Science.gov (United States)

Vergara-Perez, Sandra; Marucho, Marcelo

2016-01-01

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

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

NARCIS (Netherlands)

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

2013-01-01

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

Electrokinetic label-free screening chip: a marriage of multiplexing and high throughput analysis using surface plasmon resonance imaging

NARCIS (Netherlands)

Krishnamoorthy, G.; Carlen, Edwin; Bomer, Johan G.; Wijnperle, Daniël; de Boer, Hans L.; van den Berg, Albert; Schasfoort, Richardus B.M.

2010-01-01

We present an electrokinetic label-free biomolecular screening chip (Glass/PDMS) to screen up to 10 samples simultaneously using surface plasmon resonance imaging (iSPR). This approach reduces the duration of an experiment when compared to conventional experimental methods. This new device offers a

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.

Screens in ovoids of a Selectron cervix applicator

International Nuclear Information System (INIS)

Meertens, H.; Laarse, R. van der

1985-01-01

The addition of screens in the vaginal source holders of a cervix applicator for intracavitary brachytherapy reduces the dose to rectum and bladder and therefore diminishes the number of rectal and vesical complications. Shielding properties of tungsten rectal and bladder screens of a Selectron cervix applicator, loaded with spherical cesium sources, were determined for verification of dose calculations. The accuracy of the new screen correction algorithm of the Selectron Planning System was assessed by comparing measured and calculated dose rates and was found to be better than +-4%. The correction algorithm provides a method to analyse the efficacy of screens in the ovoids for various segment geometries and orientations without extensive phantom measurements. Isotransmission and isodose calculations were made for a typical clinical applicator set-up and source distribution. The dose reduction to rectum and bladder, near the bottom and top of the ovoids was analysed in detail. Shielding properties of a Selectron cervix applicator, provided with screens, were compared with those of some Fletcher-type applicators. Significant differences between the transmission ratios and shielded areas of the screens of both systems near rectum and bladder were observed. (Auth.)

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.

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

Directory of Open Access Journals (Sweden)

Clarisse Gravina Ricci

2018-02-01

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

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

Science.gov (United States)

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

2018-01-01

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

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

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

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.

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...

Perspective: Markov models for long-timescale biomolecular dynamics

International Nuclear Information System (INIS)

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

2014-01-01

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

Perspective: Markov models for long-timescale biomolecular dynamics

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-07

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

Field effect of screened charges: electrical detection of peptides and proteins by a thin-film resistor.

Science.gov (United States)

Lud, Simon Q; Nikolaides, Michael G; Haase, Ilka; Fischer, Markus; Bausch, Andreas R

2006-02-13

For many biotechnological applications the label-free detection of biomolecular interactions is becoming of outstanding importance. In this Article we report the direct electrical detection of small peptides and proteins by their intrinsic charges using a biofunctionalized thin-film resistor. The label-free selective and quantitative detection of small peptides and proteins is achieved using hydrophobized silicon-on-insulator (SOI) substrates functionalized with lipid membranes that incorporate metal-chelating lipids. The response of the nanometer-thin conducting silicon film to electrolyte screening effects is taken into account to determine quantitatively the charges of peptides. It is even possible to detect peptides with a single charge and to distinguish single charge variations of the analytes even in physiological electrolyte solutions. As the device is based on standard semiconductor technologies, parallelization and miniaturization of the SOI-based biosensor is achievable by standard CMOS technologies and thus a promising basis for high-throughput screening or biotechnological applications.

Review of MEMS differential scanning calorimetry for biomolecular study

Science.gov (United States)

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

2017-12-01

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

Integrated Spintronic Platforms for Biomolecular Recognition Detection

Science.gov (United States)

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

2008-06-01

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

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.

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.

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.

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.

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.

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

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

Directory of Open Access Journals (Sweden)

Giulio Caravagna

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

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

Science.gov (United States)

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

2013-01-01

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

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.

Applications of ambient mass spectrometry in high-throughput screening.

Science.gov (United States)

Li, Li-Ping; Feng, Bao-Sheng; Yang, Jian-Wang; Chang, Cui-Lan; Bai, Yu; Liu, Hu-Wei

2013-06-07

The development of rapid screening and identification techniques is of great importance for drug discovery, doping control, forensic identification, food safety and quality control. Ambient mass spectrometry (AMS) allows rapid and direct analysis of various samples in open air with little sample preparation. Recently, its applications in high-throughput screening have been in rapid progress. During the past decade, various ambient ionization techniques have been developed and applied in high-throughput screening. This review discusses typical applications of AMS, including DESI (desorption electrospray ionization), DART (direct analysis in real time), EESI (extractive electrospray ionization), etc., in high-throughput screening (HTS).

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.

Photonic crystal materials and their application in biomedicine.

Science.gov (United States)

Chen, Huadong; Lou, Rong; Chen, Yanxiao; Chen, Lili; Lu, Jingya; Dong, Qianqian

2017-11-01

Photonic crystal (PC) materials exhibit unique structural colors that originate from their intrinsic photonic band gap. Because of their highly ordered structure and distinct optical characteristics, PC-based biomaterials have advantages in the multiplex detection, biomolecular screening and real-time monitoring of biomolecules. In addition, PCs provide good platforms for drug loading and biomolecule modification, which could be applied to biosensors and biological carriers. A number of methods are now available to fabricate PC materials with variable structure colors, which could be applied in biomedicine. Emphasis is given to the description of various applications of PC materials in biomedicine, including drug delivery, biodetection and tumor screening. We believe that this article will promote greater communication among researchers in the fields of chemistry, material science, biology, medicine and pharmacy.

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

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

Science.gov (United States)

Papini, Christina; Royer, Catherine A

2018-02-01

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

GROMOS++Software for the Analysis of Biomolecular Simulation Trajectories

NARCIS (Netherlands)

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

2011-01-01

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

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

Science.gov (United States)

Shrot, Yoav; Frydman, Lucio

2011-04-01

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

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

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...

Biomolecular ligands screening using radiation damping difference WaterLOGSY spectroscopy

International Nuclear Information System (INIS)

Sun Peng; Jiang Xianwang; Jiang Bin; Zhang Xu; Liu Maili

2013-01-01

Water-ligand observed via gradient spectroscopy (WaterLOGSY) is a widely used nuclear magnetic resonance method for ligand screening. The crucial procedure for the effectiveness of WaterLOGSY is selective excitation of the water resonance. The selective excitation is conventionally achieved by using long selective pulse, which causes partial saturation of the water magnetization leading to reduction of sensitivity, in addition to time consuming and error prone. Therefore, many improvements have been made to enhance the sensitivity and robustness of the method. Here we propose an alternative selective excitation scheme for WaterLOGSY by utilizing radiation damping effect. The pulse scheme starts simply with a hard inversion pulse, instead of selective pulse or pulse train, followed by a pulse field gradient to control the radiation damping effect. The rest parts of the pulse scheme are similar to conventional WaterLOGSY. When the gradient pulse is applied immediately after the inversion pulse, the radiation damping effect is suppressed, and all of the magnetization is inversed. When the gradient pulse and the inversion pulse are about 10–20 ms apart, the radiation damping effect remains active and drives the water magnetization toward +z-axis, resulting in selective non-inversion of the water magnetization. By taking the differences of the spectra obtained under these two conditions, one should get the result of WaterLOGSY. The method is demonstrated to be simple, robust and sensitive for ligand screening

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...

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.

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

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.

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

Science.gov (United States)

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

2014-11-04

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

Affinity Capillary Electrophoresis – A Powerful Tool to Investigate Biomolecular Interactions

Czech Academy of Sciences Publication Activity Database

Kašička, Václav

2017-01-01

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

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.

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

Screening of synfuel processes for HTGR application

International Nuclear Information System (INIS)

1981-02-01

The aim of this study is to select for further study, the several synfuel processes which are the most attractive for application of HTGR heat and energy. In pursuing this objective, the Working Group identified 34 candidate synfuel processes, cut the number of processes to 16 in an initial screening, established 11 prime criteria with weighting factors for use in screening the remaining processes, developed a screening methodology and assumptions, collected process energy requirement information, and performed a comparative rating of the processes. As a result of this, three oil shale retorting processes, two coal liquefaction processes and one coal gasification process were selected as those of most interest for further study at this time

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.

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.

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

Peptide Binding to HLA Class I Molecules: Homogenous, High-Throughput Screening, and Affinity Assays

DEFF Research Database (Denmark)

Harndahl, Mikkel; Justesen, Sune Frederik Lamdahl; Lamberth, Kasper

2009-01-01

, better signal-to-background ratios, and a higher capacity. They also describe an efficient approach to screen peptides for binding to HLA molecules. For the occasional user, this will serve as a robust, simple peptide-HLA binding assay. For the more dedicated user, it can easily be performed in a high-throughput...... the luminescent oxygen channeling immunoassay technology (abbreviated LOCI and commercialized as AlphaScreen (TM)). Compared with an enzyme-linked immunosorbent assay-based peptide-HLA class I binding assay, the LOCI assay yields virtually identical affinity measurements, although having a broader dynamic range...... screening mode using standard liquid handling robotics and 384-well plates. We have successfully applied this assay to more than 60 different HLA molecules, leading to more than 2 million measurements. (Journal of Biomolecular Screening 2009: 173-180)...

Aptamer-Based Technologies in Foodborne Pathogen Detection.

Science.gov (United States)

Teng, Jun; Yuan, Fang; Ye, Yingwang; Zheng, Lei; Yao, Li; Xue, Feng; Chen, Wei; Li, Baoguang

2016-01-01

Aptamers are single stranded DNA or RNA ligands, which can be selected by a method called systematic evolution of ligands by exponential enrichment (SELEX); and they can specifically recognize and bind to their targets. These unique characteristics of aptamers offer great potentials in applications such as pathogen detection and biomolecular screening. Pathogen detection is the critical means in detecting and identifying the problems related to public health and food safety; and only the rapid, sensitive and efficient detection technologies can enable the users to make the accurate assessments on the risks of infections (humans and animals) or contaminations (foods and other commodities) caused by various pathogens. This article reviews the development in the field of the aptamer-based approaches for pathogen detection, including whole-cell SELEX and Genomic SELEX. Nowadays, a variety of aptamer-based biosensors have been developed for pathogen detection. Thus, in this review, we also cover the development in aptamer-based biosensors including optical biosensors for multiple pathogen detection by multiple-labeling or label-free models such as fluorescence detection and surface plasmon resonance, electrochemical biosensors and lateral chromatography test strips, and their applications in pathogen detection and biomolecular screening. While notable progress has been made in the field in the last decade, challenges or drawbacks in their applications such as pathogen detection and biomolecular screening remain to be overcome.

Aptamer-Based Technologies in Foodborne Pathogen Detection

Directory of Open Access Journals (Sweden)

Jun Teng

2016-09-01

Full Text Available Aptamers are single stranded DNA or RNA ligands, which can be selected by a method called systematic evolution of ligands by exponential enrichment (SELEX; and they can specifically recognize and bind to their targets. These unique characteristics of aptamers offer great potentials in applications such as pathogen detection and biomolecular screening. Pathogen detection is the first and critical means in detecting and identifying the problems related to public health and food safety; and only the rapid, sensitive and efficient detection technologies can enable the users to make to accurate assessments on the risk of infections (humans and animals or contaminations (foods and other commodities caused by various pathogens. This article reviews the developments in the field of the aptamer-based approaches for pathogen detection, including whole-cell SELEX and Genomic SELEX. Nowadays, a variety of aptamer-based biosensors have been developed for pathogen detection. Thus, in this review, we also cover the development of aptamer-based biosensors including optical biosensors for multiple pathogen detection in multiple-labeling or label-free models such as fluorescence detection and surface plasmon resonance, electrochemical biosensors, and lateral chromatography test strips, and their applications in the pathogen detection and biomolecular screening. While notable progress has been made in the field in the last decade, challenges or drawbacks in their applications such as pathogen detection and biomolecular screening, remain to be overcome.

Application of neural networks to waste site screening

International Nuclear Information System (INIS)

Dabiri, A.E.; Garrett, M.; Kraft, T.; Hilton, J.; VanHammersveld, M.

1993-02-01

Waste site screening requires knowledge of the actual concentrations of hazardous materials and rates of flow around and below the site with time. The present approach consists primarily of drilling boreholes near contaminated sites and chemically analyzing the extracted physical samples and processing the data. This is expensive and time consuming. The feasibility of using neural network techniques to reduce the cost of waste site screening was investigated. Two neural network techniques, gradient descent back propagation and fully recurrent back propagation were utilized. The networks were trained with data received from Westinghouse Hanford Corporation. The results indicate that the network trained with the fully recurrent technique shows satisfactory generalization capability. The predicted results are close to the results obtained from a mathematical flow prediction model. It is possible to develop a new tool to predict the waste plume, thus substantially reducing the number of the bore sites and samplings. There are a variety of applications for this technique in environmental site screening and remediation. One of the obvious applications would be for optimum well siting. A neural network trained from the existing sampling data could be utilized to decide where would be the best position for the next bore site. Other applications are discussed in the report

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.

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.

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...

Expression and Purification of PI3 Kinase {alpha} and Development of an ATP Depletion and an AlphaScreen PI3 Kinase Activity Assay

DEFF Research Database (Denmark)

Boldyreff, Brigitte; Rasmussen, Tine L; Jensen, Hans H

2008-01-01

Phosphoinositide-3-kinases are important targets for drug development because many proteins in the PI3 kinase signaling pathway are mutated, hyperactivated, or overexpressed in human cancers. Here, the authors coexpressed the human class Ia PI3 kinase p110alpha catalytic domain with an N-terminal....... In parallel, a second assay format using the AlphaScreen technology was optimized to measure PI3 kinase activity. Both assay formats used should be suitable for high-throughput screening for the identification of PI3 kinase inhibitors. (Journal of Biomolecular Screening XXXX:xx-xx)....

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

Directory of Open Access Journals (Sweden)

Hassan Taghipour

2013-01-01

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

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

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.

Fragment screening by SPR and advanced application to GPCRs.

Science.gov (United States)

Shepherd, Claire A; Hopkins, Andrew L; Navratilova, Iva

2014-01-01

Surface plasmon resonance (SPR) is one of the primary biophysical methods for the screening of low molecular weight 'fragment' libraries, due to its low protein consumption and 'label-free' methodology. SPR biosensor interaction analysis is employed to both screen and confirm the binding of compounds in fragment screening experiments, as it provides accurate information on the affinity and kinetics of molecular interactions. The most advanced application of the use of SPR for fragment screening is against membrane protein drug targets, such G-protein coupled receptors (GPCRs). Biophysical GPCR assays using SPR have been validated with pharmacological measurements approximate to cell-based methods, yet provide the advantage of biophysical methods in their ability to measure the weak affinities of low molecular weight fragments. A number of SPR fragment screens against GPCRs have now been disclosed in the literature. SPR fragment screening is proving versatile to screen both thermostabilised GPCRs and solubilised wild type receptors. In this chapter, we discuss the state-of-the-art in GPCR fragment screening by SPR and the technical considerations in performing such experiments. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Integrative NMR for biomolecular research

International Nuclear Information System (INIS)

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

2016-01-01

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

Integrative NMR for biomolecular research

Energy Technology Data Exchange (ETDEWEB)

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

2016-04-15

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

Climate risk screening tools and their application: A guide to the guidance

Energy Technology Data Exchange (ETDEWEB)

Traerup, S.; Olhoff, A.

2011-07-01

Climate risk screening is an integral part of efforts to ascertain current and future vulnerabilities and risks related to climate change. It is a prerequisite for identifying and designing adaptation measures, and an important element in the process of integrating, or mainstreaming, climate change adaptation into development project, planning and policy processes. There is an increasing demand and attention among national stakeholders in developing countries to take into account potential implications of climate variability and change for planning and prioritizing of development strategies and activities. Subsequently, there is a need for user friendly guidance on climate risk screening tools and their potentials for application that targets developing country stakeholders. This need is amplified by the sheer volume of climate change mainstreaming guidance documents and risk screening and assessment tools available and currently under development. Against this background, this paper sets out to provide potential users in developing countries, including project and programme developers and managers, with an informational entry point to climate risk screening tools. The emphasis in this report is on providing: 1) An overview of available climate risk screening and assessment tools along with indications of the tools available and relevant for specific purposes and contexts (Section 3). 2) Examples of application of climate risk screening and assessment tools along with links to further information (Section 4). Before turning to the respective sections on available climate risk screening tools and examples of their application, a delimitation of the tools included in this paper is included in Section 2. This section also provides a brief overview of how climate screening and related tools fit into decision making steps at various planning and decision making levels in conjunction with an outline of overall considerations to make when choosing a tool. The paper is

Application of chemical arrays in screening elastase inhibitors.

Science.gov (United States)

Gao, Feng; Du, Guan-Hua

2006-06-01

Protein chip technology provides a new and useful tool for high-throughput screening of drugs because of its high performance and low sample consumption. In order to screen elastase inhibitors on a large scale, we designed a composite microarray integrating enzyme chip containing chemical arrays on glass slides to screen for enzymatic inhibitors. The composite microarray includes an active proteinase film, screened chemical arrays distributed on the film, and substrate microarrays to demonstrate change of color. The detection principle is that elastase hydrolyzes synthetic colorless substrates and turns them into yellow products. Because yellow is difficult to detect, bromochlorophenol blue (BPB) was added into substrate solutions to facilitate the detection process. After the enzyme had catalyzed reactions for 2 h, effects of samples on enzymatic activity could be determined by detecting color change of the spots. When chemical samples inhibited enzymatic activity, substrates were blue instead of yellow products. If the enzyme retained its activity, the yellow color of the products combined with blue of BPB to make the spots green. Chromogenic differences demonstrated whether chemicals inhibited enzymatic activity or not. In this assay, 11,680 compounds were screened, and two valuable chemical hits were identified, which demonstrates that this assay is effective, sensitive and applicable for high-throughput screening (HTS).

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

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.

Biomolecular simulations on petascale: promises and challenges

International Nuclear Information System (INIS)

Agarwal, Pratul K; Alam, Sadaf R

2006-01-01

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

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

NARCIS (Netherlands)

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

2008-01-01

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

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

DEFF Research Database (Denmark)

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

2008-01-01

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

Adoption Applicants Screening: Characteristics and Challenges

Directory of Open Access Journals (Sweden)

رضا رزاقی

2018-03-01

Full Text Available Recently an increasing interest in studying and exploring the Iranian adoptive families has been evolved. Nevertheless, there are still frequent unknown factors about adoption in Iran. This study proceed to survey on characteristics of adoptive applicants due to programming and interventional needs in adoption counselling area. In this study, the descriptive survey method has been used and it involved all clients who referred to adoption counseling from March 2014 to March 2016. The clients were 411 adoptive applicants who ate-nded in semi-structured interview. Among the clients, 78% of them aimed at the adoption institutionally and 22% have followed the process illegally. Nearly half of the marriage life of infertile couples were spent to seek for infertility services. The findings indicated that nearly 27 percent of applicants are ready for adoption and other applicants require more preparation or canceling adoption process. Adoptive applicant screening process is critical and sensitive and consulting services facilitate this process; but the important point is the use of standard instrument and check-lists according to local and cultural conditions.

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

Science.gov (United States)

Sinitskiy, Anton V.; Pande, Vijay S.

2018-01-01

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

A review of current sleep screening applications for smartphones

International Nuclear Information System (INIS)

Behar, Joachim; Roebuck, Aoife; Domingos, João S; Gederi, Elnaz; Clifford, Gari D

2013-01-01

Sleep disorders are a common problem and contribute to a wide range of healthcare issues. The societal and financial costs of sleep disorders are enormous. Sleep-related disorders are often diagnosed with an overnight sleep test called a polysomnogram, or sleep study involving the measurement of brain activity through the electroencephalogram. Other parameters monitored include oxygen saturation, respiratory effort, cardiac activity (through the electrocardiogram), as well as video recording, sound and movement activity. Monitoring can be costly and removes the patients from their normal sleeping environment, preventing repeated unbiased studies. The recent increase in adoption of smartphones, with high quality on-board sensors has led to the proliferation of many sleep screening applications running on the phone. However, with the exception of simple questionnaires, no existing sleep-related application available for smartphones is based on scientific evidence. This paper reviews the existing smartphone applications landscape used in the field of sleep disorders and proposes possible advances to improve screening approaches. (topical review)

A review of current sleep screening applications for smartphones.

Science.gov (United States)

Behar, Joachim; Roebuck, Aoife; Domingos, João S; Gederi, Elnaz; Clifford, Gari D

2013-07-01

Sleep disorders are a common problem and contribute to a wide range of healthcare issues. The societal and financial costs of sleep disorders are enormous. Sleep-related disorders are often diagnosed with an overnight sleep test called a polysomnogram, or sleep study involving the measurement of brain activity through the electroencephalogram. Other parameters monitored include oxygen saturation, respiratory effort, cardiac activity (through the electrocardiogram), as well as video recording, sound and movement activity. Monitoring can be costly and removes the patients from their normal sleeping environment, preventing repeated unbiased studies. The recent increase in adoption of smartphones, with high quality on-board sensors has led to the proliferation of many sleep screening applications running on the phone. However, with the exception of simple questionnaires, no existing sleep-related application available for smartphones is based on scientific evidence. This paper reviews the existing smartphone applications landscape used in the field of sleep disorders and proposes possible advances to improve screening approaches.

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.

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.

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.

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

Science.gov (United States)

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

2017-08-01

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

Biomolecular 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

Estimation of the applicability domain of kernel-based machine learning models for virtual screening

Directory of Open Access Journals (Sweden)

Fechner Nikolas

2010-03-01

Full Text Available Abstract Background The virtual screening of large compound databases is an important application of structural-activity relationship models. Due to the high structural diversity of these data sets, it is impossible for machine learning based QSAR models, which rely on a specific training set, to give reliable results for all compounds. Thus, it is important to consider the subset of the chemical space in which the model is applicable. The approaches to this problem that have been published so far mostly use vectorial descriptor representations to define this domain of applicability of the model. Unfortunately, these cannot be extended easily to structured kernel-based machine learning models. For this reason, we propose three approaches to estimate the domain of applicability of a kernel-based QSAR model. Results We evaluated three kernel-based applicability domain estimations using three different structured kernels on three virtual screening tasks. Each experiment consisted of the training of a kernel-based QSAR model using support vector regression and the ranking of a disjoint screening data set according to the predicted activity. For each prediction, the applicability of the model for the respective compound is quantitatively described using a score obtained by an applicability domain formulation. The suitability of the applicability domain estimation is evaluated by comparing the model performance on the subsets of the screening data sets obtained by different thresholds for the applicability scores. This comparison indicates that it is possible to separate the part of the chemspace, in which the model gives reliable predictions, from the part consisting of structures too dissimilar to the training set to apply the model successfully. A closer inspection reveals that the virtual screening performance of the model is considerably improved if half of the molecules, those with the lowest applicability scores, are omitted from the screening

Estimation of the applicability domain of kernel-based machine learning models for virtual screening.

Science.gov (United States)

Fechner, Nikolas; Jahn, Andreas; Hinselmann, Georg; Zell, Andreas

2010-03-11

The virtual screening of large compound databases is an important application of structural-activity relationship models. Due to the high structural diversity of these data sets, it is impossible for machine learning based QSAR models, which rely on a specific training set, to give reliable results for all compounds. Thus, it is important to consider the subset of the chemical space in which the model is applicable. The approaches to this problem that have been published so far mostly use vectorial descriptor representations to define this domain of applicability of the model. Unfortunately, these cannot be extended easily to structured kernel-based machine learning models. For this reason, we propose three approaches to estimate the domain of applicability of a kernel-based QSAR model. We evaluated three kernel-based applicability domain estimations using three different structured kernels on three virtual screening tasks. Each experiment consisted of the training of a kernel-based QSAR model using support vector regression and the ranking of a disjoint screening data set according to the predicted activity. For each prediction, the applicability of the model for the respective compound is quantitatively described using a score obtained by an applicability domain formulation. The suitability of the applicability domain estimation is evaluated by comparing the model performance on the subsets of the screening data sets obtained by different thresholds for the applicability scores. This comparison indicates that it is possible to separate the part of the chemspace, in which the model gives reliable predictions, from the part consisting of structures too dissimilar to the training set to apply the model successfully. A closer inspection reveals that the virtual screening performance of the model is considerably improved if half of the molecules, those with the lowest applicability scores, are omitted from the screening. The proposed applicability domain formulations

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.

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.

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

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

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

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.

Biomolecular ions in superfluid helium nanodroplets

Energy Technology Data Exchange (ETDEWEB)

Gonzalez Florez, Ana Isabel

2016-07-01

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

Biomolecular ions in superfluid helium nanodroplets

International Nuclear Information System (INIS)

Gonzalez Florez, Ana Isabel

2016-01-01

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

Protein crystallization with microseed matrix screening: application to human germline antibody Fabs

International Nuclear Information System (INIS)

Obmolova, Galina; Malia, Thomas J.; Teplyakov, Alexey; Sweet, Raymond W.; Gilliland, Gary L.

2014-01-01

The power of microseed matrix screening is demonstrated in the crystallization of a panel of antibody Fab fragments. The crystallization of 16 human antibody Fab fragments constructed from all pairs of four different heavy chains and four different light chains was enabled by employing microseed matrix screening (MMS). In initial screening, diffraction-quality crystals were obtained for only three Fabs, while many Fabs produced hits that required optimization. Application of MMS, using the initial screens and/or refinement screens, resulted in diffraction-quality crystals of these Fabs. Five Fabs that failed to give hits in the initial screen were crystallized by cross-seeding MMS followed by MMS optimization. The crystallization protocols and strategies that resulted in structure determination of all 16 Fabs are presented. These results illustrate the power of MMS and provide a basis for developing future strategies for macromolecular crystallization

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)

Facilitating mental health screening of war-torn populations using mobile applications.

Science.gov (United States)

Hashemi, Bahar; Ali, Sara; Awaad, Rania; Soudi, Laila; Housel, Lawrence; Sosebee, Stephen J

2017-01-01

War-torn populations are often hard to screen for mental health disorders. Classical data collection approaches, such as paper-based, online, or SMS-operated, are either infeasible or lack accuracy due to a variety of challenges associated with dynamics and consequences of war. In this paper, we introduce a novel approach for accurate and fast screening using free open-source software, Open Data Kit (ODK) mobile application. This approach was developed by the Palestine Children's Relief Fund (PCRF) to assess the mental health symptoms of 986 Palestinian children (age 6-18) in the aftermath of Israel's Operation Protective Edge (OPE) in 2014. The organization developed assessment questionnaires and trained local field workers on the use of the mobile application, and on recruiting and interviewing war victims. War-affected children were found to suffer from several alarming symptoms associated with post-traumatic stress disorder (PTSD), depression, and somatic symptoms. Children with highest number of psychological symptoms were referred for further evaluation and treatment. The use of ODK mobile technologies facilitated efficient screening of affected children in war zones. The offline data collection capability was crucial for handling the difficult conditions associated with war-torn areas, enabling timely intervention for urgent cases. Further applications of the novel mobile technology are to be explored.

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

International Nuclear Information System (INIS)

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

2016-01-01

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

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

Science.gov (United States)

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

2016-02-22

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-05-15

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

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

Science.gov (United States)

Mailloux, Shay; Halámek, Jan; Katz, Evgeny

2014-03-07

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

[Application of liquid chromatography-high resolution mass spectrometry in toxicological screening].

Science.gov (United States)

Li, Xiao-Wen; Shen, Bao-Hua; Zhuo, Xian-Yi

2011-10-01

Due to the diversity of toxicologically relevant substances, the uncertainty of target compounds and the specificity of samples, toxicological screening techniques have always been valued by the forensic toxicologists. Depending on its powerful separation ability, superhigh resolution and accurate mass measurement, combined with the two levels spectrum database matching and abundance ratio of isotope ion, the liquid chromatography-high resolution mass spectrometry (LC-HRMS) analyzers have increasingly advantage in screening and identification of chemical compound. This review focuses on the applications of LC-HRMS in screening and identification of drug-of-abuse, prescription drugs, pesticide and stimulant. The prospect of LC-HRMS in forensic toxicology analysis is also included.

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.

Biomolecular Markers in Cancer of the Tongue

Directory of Open Access Journals (Sweden)

Daris Ferrari

2009-01-01

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

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

Science.gov (United States)

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

2017-09-01

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

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

Czech Academy of Sciences Publication Activity Database

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

2012-01-01

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

Integration of biomolecular logic gates with field-effect transducers

Energy Technology Data Exchange (ETDEWEB)

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

2011-11-01

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

Integration of biomolecular logic gates with field-effect transducers

International Nuclear Information System (INIS)

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

2011-01-01

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

Hazard screening application guide

International Nuclear Information System (INIS)

1992-06-01

The basic purpose of hazard screening is to group precesses, facilities, and proposed modifications according to the magnitude of their hazards so as to determine the need for and extent of follow on safety analysis. A hazard is defined as a material, energy source, or operation that has the potential to cause injury or illness in human beings. The purpose of this document is to give guidance and provide standard methods for performing hazard screening. Hazard screening is applied to new and existing facilities and processes as well as to proposed modifications to existing facilities and processes. The hazard screening process evaluates an identified hazards in terms of the effects on people, both on-site and off-site. The process uses bounding analyses with no credit given for mitigation of an accident with the exception of certain containers meeting DOT specifications. The process is restricted to human safety issues only. Environmental effects are addressed by the environmental program. Interfaces with environmental organizations will be established in order to share information

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.

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.

Application of Optical Biosensors in Small-Molecule Screening Activities

Directory of Open Access Journals (Sweden)

Wolfgang Knecht

2012-03-01

Full Text Available The last two decades have seen remarkable progress and improvements in optical biosensor systems such that those are currently seen as an important and value-adding component of modern drug screening activities. In particular the introduction of microplate-based biosensor systems holds the promise to match the required throughput without compromising on data quality thus representing a sought-after complement to traditional fluidic systems. This article aims to highlight the application of the two most prominent optical biosensor technologies, namely surface plasmon resonance (SPR and optical waveguide grating (OWG, in small-molecule screening and will present, review and discuss the advantages and disadvantages of different assay formats on these platforms. A particular focus will be on the specific advantages of the inhibition in solution assay (ISA format in contrast to traditional direct binding assays (DBA. Furthermore we will discuss different application areas for both fluidic as well as plate-based biosensor systems by considering the individual strength of the platforms.

Orientation of biomolecular assemblies in a microfluidic jet

International Nuclear Information System (INIS)

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

2010-01-01

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

ANCA: Anharmonic Conformational Analysis of Biomolecular Simulations.

Science.gov (United States)

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

2018-05-08

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

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

OpenAIRE

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

2017-01-01

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

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...

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

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

Health literacy screening instruments for eHealth applications: a systematic review.

Science.gov (United States)

Collins, Sarah A; Currie, Leanne M; Bakken, Suzanne; Vawdrey, David K; Stone, Patricia W

2012-06-01

To systematically review current health literacy (HL) instruments for use in consumer-facing and mobile health information technology screening and evaluation tools. The databases, PubMed, OVID, Google Scholar, Cochrane Library and Science Citation Index, were searched for health literacy assessment instruments using the terms "health", "literacy", "computer-based," and "psychometrics". All instruments identified by this method were critically appraised according to their reported psychometric properties and clinical feasibility. Eleven different health literacy instruments were found. Screening questions, such as asking a patient about his/her need for assistance in navigating health information, were evaluated in seven different studies and are promising for use as a valid, reliable, and feasible computer-based approach to identify patients that struggle with low health literacy. However, there was a lack of consistency in the types of screening questions proposed. There is also a lack of information regarding the psychometric properties of computer-based health literacy instruments. Only English language health literacy assessment instruments were reviewed and analyzed. Current health literacy screening tools demonstrate varying benefits depending on the context of their use. In many cases, it seems that a single screening question may be a reliable, valid, and feasible means for establishing health literacy. A combination of screening questions that assess health literacy and technological literacy may enable tailoring eHealth applications to user needs. Further research should determine the best screening question(s) and the best synthesis of various instruments' content and methodologies for computer-based health literacy screening and assessment. Copyright © 2012 Elsevier Inc. All rights reserved.

Health Literacy Screening Instruments for eHealth Applications: A Systematic Review

Science.gov (United States)

Collins, Sarah A.; Currie, Leanne M.; Bakken, Suzanne; Vawdrey, David K.; Stone, Patricia W.

2012-01-01

Objective To systematically review current health literacy (HL) instruments for use in consumer-facing and mobile health information technology screening and evaluation tools. Design The databases, PubMed, OVID, Google Scholar, Cochrane Library and Science Citation Index, were searched for health literacy assessment instruments using the terms “health”, “literacy”, “computer-based,” and “psychometrics”. All instruments identified by this method were critically appraised according to their reported psychometric properties and clinical feasibility. Results Eleven different health literacy instruments were found. Screening questions, such as asking a patient about his/her need for assistance in navigating health information, were evaluated in 7 different studies and are promising for use as a valid, reliable, and feasible computer-based approach to identify patients that struggle with low health literacy. However, there was a lack of consistency in the types of screening questions proposed. There is also a lack of information regarding the psychometric properties of computer-based health literacy instruments. Limitations Only English language health literacy assessment instruments were reviewed and analyzed. Conclusions Current health literacy screening tools demonstrate varying benefits depending on the context of their use. In many cases, it seems that a single screening question may be a reliable, valid, and feasible means for establishing health literacy. A combination of screening questions that assess health literacy and technological literacy may enable tailoring eHealth applications to user needs. Further research should determine the best screening question(s) and the best synthesis of various instruments’ content and methodologies for computer-based health literacy screening and assessment. PMID:22521719

Wastewater screening method for evaluating applicability of zero-valent iron to industrial wastewater

International Nuclear Information System (INIS)

Lee, J.W.; Cha, D.K.; Oh, Y.K.; Ko, K.B.; Jin, S.H.

2010-01-01

This study presents a screening protocol to evaluate the applicability of the ZVI pretreatment to various industrial wastewaters of which major constituents are not identified. The screening protocol consisted of a sequential analysis of UV-vis spectrophotometry, high-performance liquid chromatograph (HPLC), and bioassay. The UV-vis and HPLC analyses represented the potential reductive transformation of unknown constituents in wastewater by the ZVI. The UV-vis and HPLC results were quantified using principal component analysis (PCA) and Euclidian distance (ED). The short-term bioassay was used to assess the increased biodegradability of wastewater constituents after ZVI treatment. The screening protocol was applied to seven different types of real industrial wastewaters. After identifying one wastewater as the best candidate for the ZVI treatment, the benefit of ZVI pretreatment was verified through continuous operation of an integrated iron-sequencing batch reactor (SBR) resulting in the increased organic removal efficiency compared to the control. The iron pretreatment was suggested as an economical option to modify some costly physico-chemical processes in the existing wastewater treatment facility. The screening protocol could be used as a robust strategy to estimate the applicability of ZVI pretreatment to a certain wastewater with unknown composition.

Application of Plagiarism Screening Software in the Chemical Engineering Curriculum

Science.gov (United States)

Cooper, Matthew E.; Bullard, Lisa G.

2014-01-01

Plagiarism is an area of increasing concern for written ChE assignments, such as laboratory and design reports, due to ease of access to text and other materials via the internet. This study examines the application of plagiarism screening software to four courses in a university chemical engineering curriculum. The effectiveness of plagiarism…

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).

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

Directory of Open Access Journals (Sweden)

S. Iachettini

2015-10-01

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

A web-based application for initial screening of living kidney donors: development, implementation and evaluation.

Science.gov (United States)

Moore, D R; Feurer, I D; Zavala, E Y; Shaffer, D; Karp, S; Hoy, H; Moore, D E

2013-02-01

Most centers utilize phone or written surveys to screen candidates who self-refer to be living kidney donors. To increase efficiency and reduce resource utilization, we developed a web-based application to screen kidney donor candidates. The aim of this study was to evaluate the use of this web-based application. Method and time of referral were tabulated and descriptive statistics summarized demographic characteristics. Time series analyses evaluated use over time. Between January 1, 2011 and March 31, 2012, 1200 candidates self-referred to be living kidney donors at our center. Eight hundred one candidates (67%) completed the web-based survey and 399 (33%) completed a phone survey. Thirty-nine percent of donors accessed the application on nights and weekends. Postimplementation of the web-based application, there was a statistically significant increase (p web-based application as opposed to telephone contact. Also, there was a significant increase (p = 0.025) in the total number of self-referrals post-implementation from 61 to 116 per month. An interactive web-based application is an effective strategy for the initial screening of donor candidates. The web-based application increased the ability to interface with donors, process them efficiently and ultimately increased donor self-referral at our center. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

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.

Graphene Tribotronics for Electronic Skin and Touch Screen Applications.

Science.gov (United States)

Khan, Usman; Kim, Tae-Ho; Ryu, Hanjun; Seung, Wanchul; Kim, Sang-Woo

2017-01-01

Graphene tribotronics is introduced for touch-sensing applications such as electronic skins and touch screens. The devices are based on a coplanar coupling of triboelectrification and current transport in graphene transistors. The touch sensors are ultrasensitive, fast, and stable. Furthermore, they are transparent and flexible, and can spatially map touch stimuli such as movement of a ball, multi-touch, etc. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

Representability of algebraic topology for biomolecules in machine learning based scoring and virtual screening.

Science.gov (United States)

Cang, Zixuan; Mu, Lin; Wei, Guo-Wei

2018-01-01

This work introduces a number of algebraic topology approaches, including multi-component persistent homology, multi-level persistent homology, and electrostatic persistence for the representation, characterization, and description of small molecules and biomolecular complexes. In contrast to the conventional persistent homology, multi-component persistent homology retains critical chemical and biological information during the topological simplification of biomolecular geometric complexity. Multi-level persistent homology enables a tailored topological description of inter- and/or intra-molecular interactions of interest. Electrostatic persistence incorporates partial charge information into topological invariants. These topological methods are paired with Wasserstein distance to characterize similarities between molecules and are further integrated with a variety of machine learning algorithms, including k-nearest neighbors, ensemble of trees, and deep convolutional neural networks, to manifest their descriptive and predictive powers for protein-ligand binding analysis and virtual screening of small molecules. Extensive numerical experiments involving 4,414 protein-ligand complexes from the PDBBind database and 128,374 ligand-target and decoy-target pairs in the DUD database are performed to test respectively the scoring power and the discriminatory power of the proposed topological learning strategies. It is demonstrated that the present topological learning outperforms other existing methods in protein-ligand binding affinity prediction and ligand-decoy discrimination.

Representability of algebraic topology for biomolecules in machine learning based scoring and virtual screening

Science.gov (United States)

Mu, Lin

2018-01-01

This work introduces a number of algebraic topology approaches, including multi-component persistent homology, multi-level persistent homology, and electrostatic persistence for the representation, characterization, and description of small molecules and biomolecular complexes. In contrast to the conventional persistent homology, multi-component persistent homology retains critical chemical and biological information during the topological simplification of biomolecular geometric complexity. Multi-level persistent homology enables a tailored topological description of inter- and/or intra-molecular interactions of interest. Electrostatic persistence incorporates partial charge information into topological invariants. These topological methods are paired with Wasserstein distance to characterize similarities between molecules and are further integrated with a variety of machine learning algorithms, including k-nearest neighbors, ensemble of trees, and deep convolutional neural networks, to manifest their descriptive and predictive powers for protein-ligand binding analysis and virtual screening of small molecules. Extensive numerical experiments involving 4,414 protein-ligand complexes from the PDBBind database and 128,374 ligand-target and decoy-target pairs in the DUD database are performed to test respectively the scoring power and the discriminatory power of the proposed topological learning strategies. It is demonstrated that the present topological learning outperforms other existing methods in protein-ligand binding affinity prediction and ligand-decoy discrimination. PMID:29309403

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.

Screening Analysis of Criticality Features, Events, and Processes for License Application

International Nuclear Information System (INIS)

J.A. McClure

2004-01-01

This report documents the screening analysis of postclosure criticality features, events, and processes. It addresses the probability of criticality events resulting from degradation processes as well as disruptive events (i.e., seismic, rock fall, and igneous). Probability evaluations are performed utilizing the configuration generator described in ''Configuration Generator Model'', a component of the methodology from ''Disposal Criticality Analysis Methodology Topical Report''. The total probability per package of criticality is compared against the regulatory probability criterion for inclusion of events established in 10 CFR 63.114(d) (consider only events that have at least one chance in 10,000 of occurring over 10,000 years). The total probability of criticality accounts for the evaluation of identified potential critical configurations of all baselined commercial and U.S. Department of Energy spent nuclear fuel waste form and waste package combinations, both internal and external to the waste packages. This criticality screening analysis utilizes available information for the 21-Pressurized Water Reactor Absorber Plate, 12-Pressurized Water Reactor Absorber Plate, 44-Boiling Water Reactor Absorber Plate, 24-Boiling Water Reactor Absorber Plate, and the 5-Defense High-Level Radioactive Waste/U.S. Department of Energy Short waste package types. Where defensible, assumptions have been made for the evaluation of the following waste package types in order to perform a complete criticality screening analysis: 21-Pressurized Water Reactor Control Rod, 5-Defense High-Level Radioactive Waste/U.S. Department of Energy Long, and 2-Multi-Canister Overpack/2-Defense High-Level Radioactive Waste package types. The inputs used to establish probabilities for this analysis report are based on information and data generated for the Total System Performance Assessment for the License Application, where available. This analysis report determines whether criticality is to be

Initial Screening of Environmentally Sustainable Surface Pretreatments for Adhesive Bonding Applications

Science.gov (United States)

2017-05-17

13. SUPPLEMENTARY NOTES 14. ABSTRACT A methacrylate adhesive marketed for high-temperature applications was screened in combination with...conditioning = RT. Mode-of-failure = mixed - mode (MM). ........................................................................................ 26 Fig. B-3...moisture exposure conditions. Additionally, as environmental regulations force various chemicals from the commercial market , the pretreatments and

The Effect of Screen Size on Mobile Phone User Comprehension of Health Information and Application Structure: An Experimental Approach.

Science.gov (United States)

Al Ghamdi, Ebtisam; Yunus, Faisal; Da'ar, Omar; El-Metwally, Ashraf; Khalifa, Mohamed; Aldossari, Bakheet; Househ, Mowafa

2016-01-01

This research analyzes the impact of mobile phone screen size on user comprehension of health information and application structure. Applying experimental approach, we asked randomly selected users to read content and conduct tasks on a commonly used diabetes mobile application using three different mobile phone screen sizes. We timed and tracked a number of parameters, including correctness, effectiveness of completing tasks, content ease of reading, clarity of information organization, and comprehension. The impact of screen size on user comprehension/retention, clarity of information organization, and reading time were mixed. It is assumed on first glance that mobile screen size would affect all qualities of information reading and comprehension, including clarity of displayed information organization, reading time and user comprehension/retention of displayed information, but actually the screen size, in this experimental research, did not have significant impact on user comprehension/retention of the content or on understanding the application structure. However, it did have significant impact on clarity of information organization and reading time. Participants with larger screen size took shorter time reading the content with a significant difference in the ease of reading. While there was no significant difference in the comprehension of information or the application structures, there were a higher task completion rate and a lower number of errors with the bigger screen size. Screen size does not directly affect user comprehension of health information. However, it does affect clarity of information organization, reading time and user's ability to recall information.

A roadmap to directed enzyme evolution and screening systems for biotechnological applications

Directory of Open Access Journals (Sweden)

Ronny Martínez

2013-01-01

Full Text Available Enzymes have been long used in man-made biochemical processes, from brewing and fermentation to current industrial production of fine chemicals. The ever-growing demand for enzymes in increasingly specific applications requires tailoring naturally occurring enzymes to the non-natural conditions found in industrial processes. Relationships between enzyme sequence, structure and activity are far from understood, thus hindering the capacity to design tailored biocatalysts. In the field of protein engineering, directed enzyme evolution is a powerful algorithm to generate and identify novel and improved enzymes through iterative rounds of mutagenesis and screening applying a specific evolutive pressure. In practice, critical checkpoints in directed evolution are: selection of the starting point, generation of the mutant library, development of the screening assay and analysis of the output of the screening campaign. Each step in directed evolution can be performed using conceptually and technically different approaches, all having inherent advantages and challenges. In this article, we present and discuss in a general overview, challenges of designing and performing a directed enzyme evolution campaign, current advances in methods, as well as highlighting some examples of its applications in industrially relevant enzymes.

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

Science.gov (United States)

2017-01-01

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

web cellHTS2: A web-application for the analysis of high-throughput screening data

Directory of Open Access Journals (Sweden)

Boutros Michael

2010-04-01

Full Text Available Abstract Background The analysis of high-throughput screening data sets is an expanding field in bioinformatics. High-throughput screens by RNAi generate large primary data sets which need to be analyzed and annotated to identify relevant phenotypic hits. Large-scale RNAi screens are frequently used to identify novel factors that influence a broad range of cellular processes, including signaling pathway activity, cell proliferation, and host cell infection. Here, we present a web-based application utility for the end-to-end analysis of large cell-based screening experiments by cellHTS2. Results The software guides the user through the configuration steps that are required for the analysis of single or multi-channel experiments. The web-application provides options for various standardization and normalization methods, annotation of data sets and a comprehensive HTML report of the screening data analysis, including a ranked hit list. Sessions can be saved and restored for later re-analysis. The web frontend for the cellHTS2 R/Bioconductor package interacts with it through an R-server implementation that enables highly parallel analysis of screening data sets. web cellHTS2 further provides a file import and configuration module for common file formats. Conclusions The implemented web-application facilitates the analysis of high-throughput data sets and provides a user-friendly interface. web cellHTS2 is accessible online at http://web-cellHTS2.dkfz.de. A standalone version as a virtual appliance and source code for platforms supporting Java 1.5.0 can be downloaded from the web cellHTS2 page. web cellHTS2 is freely distributed under GPL.

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

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

Science.gov (United States)

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

2017-09-01

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

[Technology and prevention in the era of mobile health: applications for cancer screening programs].

Science.gov (United States)

Bert, Fabrizio; Gualano, Maria Rosaria; Clemente, Salvatore; Villa, Giulia; Siliquini, Roberta

2017-01-01

The Italian national health system provides screening to detect breast, colorecatal and cervical cancers, however, population adherence is not as high as expected. Smartphones and their applications (apps) could be used as a tool to communicate with the population and to help improve adherence. The aim of this study was to analyze the features and functions of smartphone applications aimed at secondary prevention of oncological diseases. In February 2016, we reviewed online app stores, using specific key-words, to search for available apps for cancer screening. We identified 32 apps meeting our inclusion criteria. The most frequent types of app are breast cancer (13/32) and cervical cancer (4/32) screening apps. We also found apps addressing secondary prevention of cancers for which screening is not provided to the Italian population (melanoma, prostate cancer and hepatocellular carcinoma). The most common features are: information providers (22/32), risk calculators (10/32), reminders for appointments and tests (7/32). Only one app has been validated for diagnostic accuracy or utility using established international certification (CE Marking). The results show a large potential for development and utilization of applications in secondary prevention. Despite their potential usefulness, there are also disadvantages such as language barriers (only 2 of 32 apps are in Italian), and the digital divide. Future efforts should focus on improving education regarding approaches to technologies, strengthen national and international regulations and monitoring inequalities in access to services.

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

Science.gov (United States)

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

2012-07-26

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

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

Science.gov (United States)

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

2013-01-01

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

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...

Virtual screening of electron acceptor materials for organic photovoltaic applications

International Nuclear Information System (INIS)

D Halls, Mathew; Giesen, David J; Goldberg, Alexander; Djurovich, Peter J; Sommer, Jonathan; McAnally, Eric; Thompson, Mark E

2013-01-01

Virtual screening involves the generation of structure libraries, automated analysis to predict properties related to application performance and subsequent screening to identify lead systems and estimate critical structure–property limits across a targeted chemical design space. This approach holds great promise for informing experimental discovery and development efforts for next-generation materials, such as organic semiconductors. In this work, the virtual screening approach is illustrated for nitrogen-substituted pentacene molecules to identify systems for development as electron acceptor materials for use in organic photovoltaic (OPV) devices. A structure library of tetra-azapentacenes (TAPs) was generated by substituting four nitrogens for CH at 12 sites on the pentacene molecular framework. Molecular properties (e.g. E LUMO , E g and μ) were computed for each candidate structure using hybrid DFT at the B3LYP/6-311G** level of theory. The resulting TAPs library was then analyzed with respect to intrinsic properties associated with OPV acceptor performance. Marcus reorganization energies for charge transport for the most favorable TAP candidates were then calculated to further determine suitability as OPV electron acceptors. The synthesis, characterization and OPV device testing of TAP materials is underway, guided by these results. (paper)

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

CERN Document Server

2014-01-01

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

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

International Nuclear Information System (INIS)

2016-01-01

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

Construction of RNA-Quantum Dot Chimera for Nanoscale Resistive Biomemory Application.

Science.gov (United States)

Lee, Taek; Yagati, Ajay Kumar; Pi, Fengmei; Sharma, Ashwani; Choi, Jeong-Woo; Guo, Peixuan

2015-07-28

RNA nanotechnology offers advantages to construct thermally and chemically stable nanoparticles with well-defined shape and structure. Here we report the development of an RNA-QD (quantum dot) chimera for resistive biomolecular memory application. Each QD holds two copies of the pRNA three-way junction (pRNA-3WJ) of the bacteriophage phi29 DNA packaging motor. The fixed quantity of two RNAs per QD was achieved by immobilizing the pRNA-3WJ with a Sephadex aptamer for resin binding. Two thiolated pRNA-3WJ serve as two feet of the chimera that stand on the gold plate. The RNA nanostructure served as both an insulator and a mediator to provide defined distance between the QD and gold. Immobilization of the chimera nanoparticle was confirmed with scanning tunneling microscopy. As revealed by scanning tunneling spectroscopy, the conjugated pRNA-3WJ-QD chimera exhibited an excellent electrical bistability signal for biomolecular memory function, demonstrating great potential for the development of resistive biomolecular memory and a nano-bio-inspired electronic device for information processing and computing.

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.

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.

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.

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.

Designer DNA Architectures: Applications in Nanomedicine

Directory of Open Access Journals (Sweden)

Arun Richard Chandrasekaran

2016-04-01

Full Text Available DNA has been used as a material for the construction of nanoscale objects. These nanostructures are programmable and allow the conjugation of biomolecular guests to improve their functionality. DNA nanostructures display a wide variety of characteristics, such as cellular permeabil‐ ity, biocompatibility and stability, and responsiveness to external stimuli, making them excellent candidates for applications in nanomedicine.

Ultrasound-mediated method for rapid delivery of nano-particles into cells for intracellular surface-enhanced Raman spectroscopy and cancer cell screening

International Nuclear Information System (INIS)

Feng, Shangyuan; Li, Zhihua; Chen, Guannan; Huang, Shaohua; Huang, Zufang; Li, Yongzeng; Lin, Juqiang; Chen, Rong; Lin, Duo; Zeng, Haishan

2015-01-01

Surface-enhanced Raman spectroscopy (SERS) is a powerful technology for providing finger-printing information of cells. A big challenge has been the long time duration and inefficient uptake of metal nano-particles into living cells as substrate for SERS analysis. Herein, a simple method (based on ultrasound) for the rapid transfer of silver nanoparticles (NPs) into living cells for intracellular SERS spectroscopy was presented. In this study, the ultrasound-mediated method for NP delivery overcame the shortcoming of ‘passive uptake’, and achieved quick acquisition of reproducible SERS spectra from living human nasopharyngeal carcinoma cell lines (C666 and CNE1) and normal nasopharyngeal cell line (NP69). Tentative assignment of the Raman bands in the measured SERS spectra showed cancer cell specific biomolecular differences, including significantly lower DNA concentrations and higher protein concentrations in cancerous nasopharyngeal cells as compared to those of normal cells. Combined with PCA–LDA multivariate analysis, ultrasound-mediated cell SERS spectroscopy differentiated the cancerous cells from the normal nasopharyngeal cells with high diagnostic accuracy (98.7%), demonstrating great potential for high-throughput cancer cell screening applications. (paper)

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

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...

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.

Mechanical evaluation of a new sand control screen for SAGD applications

Energy Technology Data Exchange (ETDEWEB)

Woiceshyn, G. [Society of Petroleum Engineers, Canadian Section, Calgary, AB (Canada)]|[Absolute Completion Technologies, Calgary, AB (Canada); Toffanin, E. [Society of Petroleum Engineers, Canadian Section, Calgary, AB (Canada)]|[Schlumberger Canada Ltd., Calgary, AB (Canada); Xie, J.; Wagg, B. [Society of Petroleum Engineers, Canadian Section, Calgary, AB (Canada)]|[C-FER Technologies, Edmonton, AB (Canada); Fan, C. [C-FER Technologies, Edmonton, AB (Canada)

2008-10-15

Steam assisted gravity drainage (SAGD) wells normally require the deployment of an open hole completion combining sand control with adequate mechanical strength to withstand aggressive installation loads and serve operational loads. Slotted liners have traditionally been used in western Canada, mainly because of low cost relative to wire-wrapped screen or premium mesh screens. However, slotting base pipe can weaken the mechanical strength. The slot width can also change as the liner deforms under certain load conditions. Operators are therefore interested in alternative technologies to reduce incidents of mechanical failure and loss of sand control of slotted liners in SAGD wells. This paper presented the flush absolute cartridge system (FACS), a newly developed sand screen onto which a 25.4 diameter fusion bonded metal laminate cartridge is directly mounted and secured directly into the base pipe wall. The paper discussed a finite element analysis study that was conducted in order to independently quantify its mechanical strength and integrity for use in SAGD operations. The paper described the liner, as well as the disc geometry, construction and properties. The paper also listed the potential applications for FACS screens and provided a description of the finite element analysis. It was concluded that although FACS satisfies the basic operational criteria, it has very limited ability to absorb additional strain at the end of the thermal cycle. 10 refs., 4 tabs., 22 figs.

Development of smartphone application that aids stroke screening and identifying nearby acute stroke care hospitals.

Science.gov (United States)

Nam, Hyo Suk; Heo, JoonNyung; Kim, Jinkwon; Kim, Young Dae; Song, Tae Jin; Park, Eunjeong; Heo, Ji Hoe

2014-01-01

The benefits of thrombolytic treatment are time-dependent. We developed a smartphone application that aids stroke patient self-screening and hospital selection, and may also decrease hospital arrival time. The application was developed for iPhone and Android smartphones. Map data for the application were adopted from the open map. For hospital registration, a web page (http://stroke119.org) was developed using PHP and MySQL. The Stroke 119 application includes a stroke screening tool and real-time information on nearby hospitals that provide thrombolytic treatment. It also provides information on stroke symptoms, thrombolytic treatment, and prescribed actions when stroke is suspected. The stroke screening tool was adopted from the Cincinnati Prehospital Stroke Scale and is displayed in a cartoon format. If the user taps a cartoon image that represents abnormal findings, a pop-up window shows that the user may be having a stroke, informs the user what to do, and directs the user to call emergency services. Information on nearby hospitals is provided in map and list views, incorporating proximity to the user's location using a Global Positioning System (a built-in function of smartphones). Users can search for a hospital according to specialty and treatment levels. We also developed a web page for hospitals to register in the system. Neurology training hospitals and hospitals that provide acute stroke care in Korea were invited to register. Seventy-seven hospitals had completed registration. This application may be useful for reducing hospital arrival times for thrombolytic candidates.

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

Science.gov (United States)

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

2016-06-01

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

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

Science.gov (United States)

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

2017-01-01

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

Surface-enhanced Raman spectroscopy bioanalytical, biomolecular and medical applications

CERN Document Server

Procházka, Marek

2016-01-01

This book gives an overview of recent developments in RS and SERS for sensing and biosensing considering also limitations, possibilities and prospects of this technique. Raman scattering (RS) is a widely used vibrational technique providing highly specific molecular spectral patterns. A severe limitation for the application of this spectroscopic technique lies in the low cross section of RS. Surface-enhanced Raman scattering (SERS) spectroscopy overcomes this problem by 6-11 orders of magnitude enhancement compared with the standard RS for molecules in the close vicinity of certain rough metal surfaces. Thus, SERS combines molecular fingerprint specificity with potential single-molecule sensitivity. Due to the recent development of new SERS-active substrates, labeling and derivatization chemistry as well as new instrumentations, SERS became a very promising tool for many varied applications, including bioanalytical studies and sensing. Both intrinsic and extrinsic SERS biosensing schemes have been employed to...

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

NARCIS (Netherlands)

Uusitalo, Jaakko Juhani

2016-01-01

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

Scintillation screen applications in a vacuum arc ion source with composite hydride cathode

Science.gov (United States)

Wang, X. H.; Tuo, X. G.; Yang, Z.; Peng, Y. F.; Li, J.; Lv, H. Y.; Li, J. H.; Long, J. D.

2018-05-01

Vacuum arc ion source with composite hydride cathode was developed to produce intense ion beams which can be applied in particle accelerator injections. Beam profile and beam composition are two fundamental parameters of the beam for the vacuum arc ion source in such specific applications. An aluminum-coated scintillation screen with an ICCD camera readout was used to show the space-time distribution of the beam directly. A simple magnetic analysis assembly with the scintillation screen shows the beam composition information of this kind ion source. Some physical and technical issues are discussed and analyzed in the text.

Development and applicability of a ready-to-use PCR system for GMO screening.

Science.gov (United States)

Rosa, Sabrina F; Gatto, Francesco; Angers-Loustau, Alexandre; Petrillo, Mauro; Kreysa, Joachim; Querci, Maddalena

2016-06-15

With the growing number of GMOs introduced to the market, testing laboratories have seen their workload increase significantly. Ready-to-use multi-target PCR-based detection systems, such as pre-spotted plates (PSP), reduce analysis time while increasing capacity. This paper describes the development and applicability to GMO testing of a screening strategy involving a PSP and its associated web-based Decision Support System. The screening PSP was developed to detect all GMOs authorized in the EU in one single PCR experiment, through the combination of 16 validated assays. The screening strategy was successfully challenged in a wide inter-laboratory study on real-life food/feed samples. The positive outcome of this study could result in the adoption of a PSP screening strategy across the EU; a step that would increase harmonization and quality of GMO testing in the EU. Furthermore, this system could represent a model for other official control areas where high-throughput DNA-based detection systems are needed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characterization of SPAD Array for Multifocal High-Content Screening Applications

Directory of Open Access Journals (Sweden)

Anthony Tsikouras

2016-10-01

Full Text Available Current instruments used to detect specific protein-protein interactions in live cells for applications in high-content screening (HCS are limited by the time required to measure the lifetime. Here, a 32 × 1 single-photon avalanche diode (SPAD array was explored as a detector for fluorescence lifetime imaging (FLIM in HCS. Device parameters and characterization results were interpreted in the context of the application to determine if the SPAD array could satisfy the requirements of HCS-FLIM. Fluorescence lifetime measurements were performed using a known fluorescence standard; and the recovered fluorescence lifetime matched literature reported values. The design of a theoretical 32 × 32 SPAD array was also considered as a detector for a multi-point confocal scanning microscope.

Use of a smartphone application to screen for depression and suicide in South Korea.

Science.gov (United States)

Jang, Seung-Ho; Woo, Young Sup; Hong, Jeong-Wan; Yoon, Bo-Hyun; Hwang, Tae-Yeon; Kim, Moon-Doo; Lee, Sang-Yeol; Bahk, Won-Myong

2017-05-01

This is a cross-sectional study using a free depression and suicide screening smartphone application, which contains the data from the Center for Epidemiological Studies-Depression (CES-D) and a Suicide Behaviors Questionnaire-Revised (SBQ-R). The free application was downloaded worldwide from Apple's App Store and Android Market, and the participants who downloaded the application were actively measured. The subjects totaled 208,683 men and women. 72.6% of the subjects were females, and 81.4% of the subjects were aged between 10 and 29years. In total, 25.7% of the participants were recorded CES-D positive, and there were differences among the groups based on sex (χ2=1065.82, psuicide were as follows: depression (OR 8.92, 95% CI: 8.71-9.13), female (OR 1.39, 95% CI: 1.36-1.43), 30-49 age group (OR 2.51, 95% CI: 2.29-2.72), 50 or older age group (OR 1.48, 95% CI: 1.35-1.61), and psychiatric history (OR 1.98, 95% CI: 1.89-2.06). The smartphone application may be a useful tool for screening depression and suicide. Copyright © 2017 Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

International Nuclear Information System (INIS)

Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan; Durmus, Naside Gozde

2011-01-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

Energy Technology Data Exchange (ETDEWEB)

Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan [Department of Medicine, Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Durmus, Naside Gozde, E-mail: udemirci@rics.bwh.harvard.edu [School of Engineering and Division of Biology and Medicine, Brown University, Providence, RI (United States)

2011-09-15

Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

The Role of Retinal Imaging and Portable Screening Devices in Tele-ophthalmology Applications for Diabetic Retinopathy Management.

Science.gov (United States)

DeBuc, Delia Cabrera

2016-12-01

In the years since its introduction, retinal imaging has transformed our capability to visualize the posterior pole of the eye. Increasing practical advances in mobile technology, regular monitoring, and population screening for diabetic retinopathy management offer the opportunity for further development of cost-effective applications through remote assessment of the diabetic eye using portable retinal cameras, smart-phone-based devices and telemedicine networks. Numerous retinal imaging methods and mobile technologies in tele-ophthalmology applications have been reported for diabetic retinopathy screening and management. They provide several advantages of automation, sensitivity, specificity, portability, and miniaturization for the development of point-of-care diagnostics for eye complications in diabetes. The aim of this paper is to review the role of retinal imaging and mobile technologies in tele-ophthalmology applications for diabetic retinopathy screening and management. At large, although improvements in current technology and telemedicine services are still needed, telemedicine has demonstrated to be a worthy tool to support health caregivers in the effective management and prevention of diabetes and its complications.

Benefits of an Android Based Tablet Application in Primary Screening for Eye Diseases in a Rural Population, India.

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Imtiaz, Sayed Ahmed; Krishnaiah, Sannapaneni; Yadav, Sunil Kumar; Bharath, Balasubramaniam; Ramani, Ramanathan V

2017-04-01

To investigate the effectiveness, efficiency and cost gains in collecting patient eye health information from remote rural villages of India by trained field investigators through an Android Based Tablet Application namely 'Sankara Electronic Remote Vision Information System (SERVIS)". During January and March 2016, a population based cross-sectional study was conducted in three Indian states employing SERVIS and manual method. The SERVIS application has a 48-items survey instrument programed into the application. Data on 281 individuals were collected for each of these methods as part of screening. The demographic details of individuals between both screening methods were comparable (P>0.05). The mean time (in minutes) to screen an individual by SERVIS was significantly less when compared to manual method (6.57±1.46 versus 11.93±1.53) (P<0.0001). The efficiency of SERVIS in screening was significantly evident as 26% (n = 73) of the patients screened have been referred to campsite and 69.8% (n = 51) of those referred were visited the campsite for a detailed eye examination by an ophthalmologist. The cost of screening through SERVIS is significantly less when compared to manual method; INR 7,633 (USD 113.9) Versus INR 24,780 (USD 370). SERVIS is an effective and efficient tool in terms of patients' referral conversion to the camp site leading to timely detection of potential blinding eye conditions and their appropriate treatment. This ensures timely prevention of avoidable blindness and visual impairment. In addition, the storage and access of eye health epidemiological quality data is helpful to plan appropriate blindness prevention initiatives in rural India.

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

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José Augusto R. Rodrigues

2010-01-01

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

Challenges for Super-Resolution Localization Microscopy and Biomolecular Fluorescent Nano-Probing in Cancer Research

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Ilić, Nataša; Pilarczyk, Götz; Lee, Jin-Ho; Logeswaran, Abiramy; Borroni, Aurora Paola; Krufczik, Matthias; Theda, Franziska; Waltrich, Nadine; Bestvater, Felix; Hildenbrand, Georg; Cremer, Christoph; Blank, Michael

2017-01-01

Understanding molecular interactions and regulatory mechanisms in tumor initiation, progression, and treatment response are key requirements towards advanced cancer diagnosis and novel treatment procedures in personalized medicine. Beyond decoding the gene expression, malfunctioning and cancer-related epigenetic pathways, investigations of the spatial receptor arrangements in membranes and genome organization in cell nuclei, on the nano-scale, contribute to elucidating complex molecular mechanisms in cells and tissues. By these means, the correlation between cell function and spatial organization of molecules or molecular complexes can be studied, with respect to carcinogenesis, tumor sensitivity or tumor resistance to anticancer therapies, like radiation or antibody treatment. Here, we present several new applications for bio-molecular nano-probes and super-resolution, laser fluorescence localization microscopy and their potential in life sciences, especially in biomedical and cancer research. By means of a tool-box of fluorescent antibodies, green fluorescent protein (GFP) tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors in membranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2) in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by radiation or antibody treatment. The main purpose of this article is to demonstrate how nano-scaled distance measurements between bio-molecules, tagged by appropriate nano-probes, can be applied to elucidate structures and conformations of molecular complexes which are characteristic of tumorigenesis and treatment responses. These applications open new avenues towards a better interpretation of the spatial organization and treatment responses of functionally relevant molecules, at the single cell level, in normal and cancer cells, offering new potentials for individualized medicine. PMID:28956810

Challenges for Super-Resolution Localization Microscopy and Biomolecular Fluorescent Nano-Probing in Cancer Research

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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.

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

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Seibert, Jakob; Bannwarth, Christoph; Grimme, Stefan

2017-08-30

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

The Baker system for nuclear access authorization screening: a psychologically developed system for access screening of vendor and owner applicants at nuclear power plants

International Nuclear Information System (INIS)

Baker, E.G.; Crouter, F.L.

1985-01-01

This paper presents a comprehensive screening program for unescorted access which has proven to be highly effective in determining the intergrity, trustworthiness, socialibility, behaviors and tendencies of an employee applicant--past, present and future. This procedure, designed specifically for the nuclear industry, can be used with owner or vendor applicants, and meets or exceeds all of the NRC's requirements. The Baker system has been used for nuclear selection since 1979

Combinatorial chemoenzymatic synthesis and high-throughput screening of sialosides.

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Chokhawala, Harshal A; Huang, Shengshu; Lau, Kam; Yu, Hai; Cheng, Jiansong; Thon, Vireak; Hurtado-Ziola, Nancy; Guerrero, Juan A; Varki, Ajit; Chen, Xi

2008-09-19

Although the vital roles of structures containing sialic acid in biomolecular recognition are well documented, limited information is available on how sialic acid structural modifications, sialyl linkages, and the underlying glycan structures affect the binding or the activity of sialic acid-recognizing proteins and related downstream biological processes. A novel combinatorial chemoenzymatic method has been developed for the highly efficient synthesis of biotinylated sialosides containing different sialic acid structures and different underlying glycans in 96-well plates from biotinylated sialyltransferase acceptors and sialic acid precursors. By transferring the reaction mixtures to NeutrAvidin-coated plates and assaying for the yields of enzymatic reactions using lectins recognizing sialyltransferase acceptors but not the sialylated products, the biotinylated sialoside products can be directly used, without purification, for high-throughput screening to quickly identify the ligand specificity of sialic acid-binding proteins. For a proof-of-principle experiment, 72 biotinylated alpha2,6-linked sialosides were synthesized in 96-well plates from 4 biotinylated sialyltransferase acceptors and 18 sialic acid precursors using a one-pot three-enzyme system. High-throughput screening assays performed in NeutrAvidin-coated microtiter plates show that whereas Sambucus nigra Lectin binds to alpha2,6-linked sialosides with high promiscuity, human Siglec-2 (CD22) is highly selective for a number of sialic acid structures and the underlying glycans in its sialoside ligands.

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

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

2010-09-20

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

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

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Mary E Prendergast

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

Marked Object Recognition Multitouch Screen Printed Touchpad for Interactive Applications.

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Nunes, Jivago Serrado; Castro, Nelson; Gonçalves, Sergio; Pereira, Nélson; Correia, Vitor; Lanceros-Mendez, Senentxu

2017-12-01

The market for interactive platforms is rapidly growing, and touchscreens have been incorporated in an increasing number of devices. Thus, the area of smart objects and devices is strongly increasing by adding interactive touch and multimedia content, leading to new uses and capabilities. In this work, a flexible screen printed sensor matrix is fabricated based on silver ink in a polyethylene terephthalate (PET) substrate. Diamond shaped capacitive electrodes coupled with conventional capacitive reading electronics enables fabrication of a highly functional capacitive touchpad, and also allows for the identification of marked objects. For the latter, the capacitive signatures are identified by intersecting points and distances between them. Thus, this work demonstrates the applicability of a low cost method using royalty-free geometries and technologies for the development of flexible multitouch touchpads for the implementation of interactive and object recognition applications.

Marked Object Recognition Multitouch Screen Printed Touchpad for Interactive Applications

Directory of Open Access Journals (Sweden)

Jivago Serrado Nunes

2017-12-01

Full Text Available The market for interactive platforms is rapidly growing, and touchscreens have been incorporated in an increasing number of devices. Thus, the area of smart objects and devices is strongly increasing by adding interactive touch and multimedia content, leading to new uses and capabilities. In this work, a flexible screen printed sensor matrix is fabricated based on silver ink in a polyethylene terephthalate (PET substrate. Diamond shaped capacitive electrodes coupled with conventional capacitive reading electronics enables fabrication of a highly functional capacitive touchpad, and also allows for the identification of marked objects. For the latter, the capacitive signatures are identified by intersecting points and distances between them. Thus, this work demonstrates the applicability of a low cost method using royalty-free geometries and technologies for the development of flexible multitouch touchpads for the implementation of interactive and object recognition applications.

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

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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.

Application of Suresight handheld auto-refractometer in refraction screening for infants in Community Health Service Center

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Li-Hua Guo

2014-08-01

Full Text Available AIM: To observe the application of Suresight handheld auto-refractometer in measuring diopter of infants in Community Health Service Center. METHODS:Totally 836 cases(1 672 eyesfrom June 2013 to December 2013 were examined diopter of infants by Suresight handheld auto-refractometer in Community Health Service Center. RESULTS: Within 1 672 eyes of 836 infants were examined, 202 eyes were diagnosed ametropia, 38 eyes were suspicious, 240 eyes were transferred to the department of ophthalmology, the referral rate was 14.35%; 172 eyes were diagnosed ametropia, and the diagnosis rate of the referral patients was 71.67%. Among 172 eyes, 46 eyes were provided with corrected glasses, accounting for 2.75% of the number of screening, and 126 eyes were given intensive monitoring, accounting for 7.54% of the number of screening.CONCLUSION: Application of Suresight handheld auto-refractometer in refraction screening for infants in Community Health Service Center is convenient and effective. With two-way referral between community health service center and department of ophthalmology can monitor and intervene vision development of infants much earlier.

Screening applications in drug discovery based on microfluidic technology

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Eribol, P.; Uguz, A. K.; Ulgen, K. O.

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

Screening applications in drug discovery based on microfluidic technology.

Science.gov (United States)

Eribol, P; Uguz, A K; Ulgen, K O

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

Application of ultrasound in fetal cardiac abnormalitis screening and analyzing of influencing factors

International Nuclear Information System (INIS)

Wu Wei; Chen Hui; Guo Hua; Fu Lijuan

2009-01-01

Objective: To identify the application value of ultrasound in the screening of fetal cardiac abnormalities and to reduce its affecting factors, in order to maximally decrease the birth of oaf. Methods: Adopting the method of four chamber hearts cross-section and sound beam plane head laterodeviation, 3821 fetal hearts were screened by ultrasonocardiography in middle and late fetal period. The influencing factors were also analyzed. Screening results were compared with the autopsy following induced labor and the ultrasonocardiogram after borne. Results: Total 23 cases of the cardiac anomalies were confirmed by odinopoeia or after borned, 21 cases were diagnosed by antepartum ultrasonocardiography, the detectable rate were 91.3%(21/23). And the complex cardiac anomalies were 19 cases, accounted for 82.61%(19/23), the general malformation were 4 cases, accounted for 17.39%(4/23). In 19 cases of the complex anomalies, 17 cases were diagnosed by antepartum examination in the first time, 2 cases were diagnosed by reexamination, the total detectable rate were 100%(19/19). Conclusion: Ultrasonography is not only non-invasive but also unique method in detecting fetal heart defects. It will help to diagnose definitely the vast majority of congenital malformation in the fetal heart, especially complex malformation in the middle and later fetal period. There are some limitations and chronergy in ultrasonography for the screening of fetal heart defects, which should be followed-up when the fetal appeared 'normal' in the early screening. (authors)

HERCA WG Medical Applications / Sub WG 'Exposure of Asymptomatic Individuals in Health Care' - 'Position Paper on Screening'

International Nuclear Information System (INIS)

Griebel, Juergen; Ebdon-Jackson, Steve

2012-05-01

Over the course of several meetings the HERCA-Working Group (WG) 'Medical Applications' has discussed the exposure of asymptomatic individuals in health care. In particular, the discussions focused on the issue of the early detection of severe diseases, by use of X-rays, for those who do not present with symptoms. An important and established example is the use of X-ray mammography to detect early breast cancer and this has traditionally been referred to as screening. An emerging application is the use of computed tomography in a range of circumstances, some of which may be better described as a separate category of medical exposure as they are neither diagnostic nor screening in the accepted sense. The discussions have indicated that it is pivotal to clearly define the relevant terms generally applied and to clearly differentiate these terms from diagnostic examinations used in health care. In this context, it is important to note, that the revision of the Euratom Basic Safety Standards (Euratom BSS) Directive is under way and addresses in particular medical radiological procedures on asymptomatic individuals, intended to be performed for early detection of disease (Draft Proposal 29 September 2011 Article 54). Hereby, two types of examinations of asymptomatic individuals, (that in some cases have both been referred to as screening) are addressed: (1) exposures as part of screening programmes and (2) exposures associated with individual health assessment. On adoption, this directive will have significant implications for and a substantial impact on the work of the radiation protection authorities in Europe. In this position paper the WG 'Medical Applications' proposes a clear distinction between screening and radiological procedures as part of an individual health assessment and highlights special requirements for the latter. Finally, the impact on the work of radiation protection authorities in Europe is addressed

Single-molecule experiments in biological physics: methods and applications.

Science.gov (United States)

Ritort, F

2006-08-16

I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

Single-molecule experiments in biological physics: methods and applications

International Nuclear Information System (INIS)

Ritort, F

2006-01-01

I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives. (topical review)

Automated Groundwater Screening

International Nuclear Information System (INIS)

Taylor, Glenn A.; Collard, Leonard B.

2005-01-01

The Automated Intruder Analysis has been extended to include an Automated Ground Water Screening option. This option screens 825 radionuclides while rigorously applying the National Council on Radiation Protection (NCRP) methodology. An extension to that methodology is presented to give a more realistic screening factor for those radionuclides which have significant daughters. The extension has the promise of reducing the number of radionuclides which must be tracked by the customer. By combining the Automated Intruder Analysis with the Automated Groundwater Screening a consistent set of assumptions and databases is used. A method is proposed to eliminate trigger values by performing rigorous calculation of the screening factor thereby reducing the number of radionuclides sent to further analysis. Using the same problem definitions as in previous groundwater screenings, the automated groundwater screening found one additional nuclide, Ge-68, which failed the screening. It also found that 18 of the 57 radionuclides contained in NCRP Table 3.1 failed the screening. This report describes the automated groundwater screening computer application

Discoveries and application of prostate-specific antigen, and some proposals to optimize prostate cancer screening

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Tokudome S

2016-05-01

Full Text Available Shinkan Tokudome,1 Ryosuke Ando,2 Yoshiro Koda,3 1Department of Nutritional Epidemiology, National Institute of Health and Nutrition, Shinjuku-ku, Tokyo, 2Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, 3Department of Forensic Medicine and Human Genetics, Kurume University School of Medicine, Kurume, Japan Abstract: The discoveries and application of prostate-specific antigen (PSA have been much appreciated because PSA-based screening has saved millions of lives of prostate cancer (PCa patients. Historically speaking, Flocks et al first identified antigenic properties in prostate tissue in 1960. Then, Barnes et al detected immunologic characteristics in prostatic fluid in 1963. Hara et al characterized γ-semino-protein in semen in 1966, and it has been proven to be identical to PSA. Subsequently, Ablin et al independently reported the presence of precipitation antigens in the prostate in 1970. Wang et al purified the PSA in 1979, and Kuriyama et al first applied an enzyme-linked immunosorbent assay for PSA in 1980. However, the positive predictive value with a cutoff figure of 4.0 ng/mL appeared substantially low (~30%. There are overdiagnoses and overtreatments for latent/low-risk PCa. Controversies exist in the PCa mortality-reducing effects of PSA screening between the European Randomized Study of Screening for Prostate Cancer (ERSPC and the US Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening Trial. For optimizing PCa screening, PSA-related items may require the following: 1 adjustment of the cutoff values according to age, as well as setting limits to age and screening intervals; 2 improving test performance using doubling time, density, and ratio of free: total PSA; and 3 fostering active surveillance for low-risk PCa with monitoring by PSA value. Other items needing consideration may include the following: 1 examinations of cell proliferation and cell cycle markers

On various metrics used for validation of predictive QSAR models with applications in virtual screening and focused library design.

Science.gov (United States)

Roy, Kunal; Mitra, Indrani

2011-07-01

Quantitative structure-activity relationships (QSARs) have important applications in drug discovery research, environmental fate modeling, property prediction, etc. Validation has been recognized as a very important step for QSAR model development. As one of the important objectives of QSAR modeling is to predict activity/property/toxicity of new chemicals falling within the domain of applicability of the developed models and QSARs are being used for regulatory decisions, checking reliability of the models and confidence of their predictions is a very important aspect, which can be judged during the validation process. One prime application of a statistically significant QSAR model is virtual screening for molecules with improved potency based on the pharmacophoric features and the descriptors appearing in the QSAR model. Validated QSAR models may also be utilized for design of focused libraries which may be subsequently screened for the selection of hits. The present review focuses on various metrics used for validation of predictive QSAR models together with an overview of the application of QSAR models in the fields of virtual screening and focused library design for diverse series of compounds with citation of some recent examples.

Biomolecular strategies for cell surface engineering

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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

Mathematical Models of the Sinusoidal Screen Family

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Tajana Koren

2011-06-01

Full Text Available In this paper we will define a family of sinusoidal screening elements and explore the possibilities of their application in graphic arts, securities printing and design solutions in photography and typography editing. For this purpose mathematical expressions of sinusoidal families were converted into a Postscript language. The introduction of a random variable results in a countless number of various mutations which cannot be repeated without knowing the programming code itself. The use of the family of screens in protection of securities is thus of great importance. Other possible application of modulated sinusoidal screens is related to the large format color printing. This paper will test the application of sinusoidal screens in vector graphics, pixel graphics and typography. The development of parameters in the sinusoidal screen element algorithms gives new forms defined within screening cells with strict requirements of coverage implementation. Individual solutions include stochastic algorithms, as well as the autonomy of screening forms in regard to multicolor printing channels.

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.

Screening for the optimal induction parameters for periplasmic ...

African Journals Online (AJOL)

ONOS

2010-09-20

Sep 20, 2010 ... 3Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, ... induce protein expression can be varied to adjust the ..... disruption in high pressure homogenizer.

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)

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

Science.gov (United States)

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

2009-10-15

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

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

Science.gov (United States)

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

2012-07-01

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

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.

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.

Application of ToxCast High-Throughput Screening and ...

Science.gov (United States)

Slide presentation at the SETAC annual meeting on High-Throughput Screening and Modeling Approaches to Identify Steroidogenesis Distruptors Slide presentation at the SETAC annual meeting on High-Throughput Screening and Modeling Approaches to Identify Steroidogenssis Distruptors

[Clinical application of M-CHAT and CHAT-23 for autism screening].

Science.gov (United States)

Ren, Shuang; Ma, Hong-Wei; Hu, Man; Wang, Li-Bo; Wang, Lin; Li, Fang; Song, Ying; Tan, Ying-Hua

2012-12-01

To analyze and compare Modified Checklist for Autism in Toddlers (M-CHAT) and Checklist for Autism in Toddlers-23 (CHAT-23) in terms of clinical applicability, and to provide a basis for the understanding of early specific clinical manifestations of children with autism. A total of 350 children aged 18-36 months who visited the Department of Developmental Pediatrics of Shengjing Hospital of China Medical University were enrolled as subjects. Of the 350 children, 284 who had not been previously diagnosed with autism were screened according to the two checklists. Sixty-eight confirmed cases of autism (including two of the 284 screening subjects diagnosed with autism) were assigned to the autism group, and 278 of the 284 screening subjects (except six children diagnosed with autism, mental retardation or cerebral palsy) were assigned to the control group. The two groups were compared with respect to the positive rate for each item in the checklists. The efficacy of the M-CHAT and CHAT-23 assessment criteria was evaluated by comparative analysis. The autism group showed the highest positive rate for Item 9. There were significant differences between the two groups in terms of the positive rates for all items except Item 16 (PCHAT showed the lowest rate of missed diagnosis (0%); when the assessment criterion was that autism was confirmed if there were positive results for at least 6 of a total of 23 items, CHAT-23 showed the lowest rate of misdiagnosis (1.77%). The specificity of M-CHAT is lower than that of CHAT-23 (P0.05). CHAT-23 is more suitable than M-CHAT for clinical autism screening due to higher specificity, as well as having the advantages of low cost, easy completion,high efficiency and easy result judgment.

MOCVD ZnO/Screen Printed Ag Back Reflector for Flexible Thin Film Silicon Solar Cell Application

Directory of Open Access Journals (Sweden)

Amornrat Limmanee

2014-01-01

Full Text Available We have prepared Ag back electrode by screen printing technique and developed MOCVD ZnO/screen printed Ag back reflector for flexible thin film silicon solar cell application. A discontinuity and poor contact interface between the MOCVD ZnO and screen printed Ag layers caused poor open circuit voltage (Voc and low fill factor (FF; however, an insertion of a thin sputtered ZnO layer at the interface could solve this problem. The n type hydrogenated amorphous silicon (a-Si:H film is preferable for the deposition on the surface of MOCVD ZnO film rather than the microcrystalline film due to its less sensitivity to textured surface, and this allowed an improvement in the FF. The n-i-p flexible amorphous silicon solar cell using the MOCVD ZnO/screen printed Ag back reflector showed an initial efficiency of 6.2% with Voc=0.86 V, Jsc=12.4 mA/cm2, and FF = 0.58 (1 cm2. The identical quantum efficiency and comparable performance to the cells using conventional sputtered Ag back electrode have verified the potential of the MOCVD ZnO/screen printed Ag back reflector and possible opportunity to use the screen printed Ag thick film for flexible thin film silicon solar cells.

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

Science.gov (United States)

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

2011-11-01

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

TOPICAL REVIEW: Single-molecule experiments in biological physics: methods and applications

Science.gov (United States)

Ritort, F.

2006-08-01

I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

Screening Criteria and Considerations of Offshore Enhanced Oil Recovery

Directory of Open Access Journals (Sweden)

Pan-Sang Kang

2016-01-01

Full Text Available The application of enhanced oil recovery (EOR in offshore oil fields has received significant attention due to the potentially enormous amount of recoverable oil. However, EOR application offshore is in its very early stage due to conditions that are more complex than onshore oil fields, owing to the unique parameters present offshore. Therefore, successful EOR applications in offshore oil fields require different screening criteria than those for conventional onshore applications. A comprehensive database for onshore applications of EOR processes together with a limited offshore EOR application database are analyzed in this paper, and the important parameters for successful offshore application are incorporated into the new EOR screening criteria. In this paper, screening criteria to determine acceptable EOR processes for offshore fields, including hydrocarbon gas miscible, CO2 miscible, and polymer processes, are presented. Suggested screening criteria for these EOR processes comprise quantitative boundaries and qualitative considerations. Quantitative screening criteria are predominantly based on quantifiable data, such as oil and reservoir properties. Qualitative screening considerations mainly focus on the operational issues present offshore, including platform space constraints, limited disposal options, injectant availability, and flow assurance matters (including hydrate formation and difficulties in emulsion separation.

Screening sensitivity theory

International Nuclear Information System (INIS)

Oblow, E.M.; Perey, F.G.

1984-01-01

A comprehensive rigorous theory is developed for screening sensitivity coefficients in largescale modeling applications. The theory uses Bayesian inference and group theory to establish a probabilistic framework for solving an underdetermined system of linear equations. The underdetermined problem is directly related to statistical screening sensitivity theory as developed in recent years. Several examples of the new approach to screening are worked out in detail and comparisons are made with statistical approaches to the problem. The drawbacks of these latter methods are discussed at some length

Low-dosage helical CT applications for chest medical checkup and lung cancer screening

International Nuclear Information System (INIS)

Wang Ping; Cui Fa; Liang Huanqing; Zheng Minfei

2005-01-01

Objective: A discussion on low-dosage helical CT applications on chest medical checkup and lung cancer screening. Methods: On the 100 chest medical check up with three different of protocols, including standard-dosage (the tube current was 230 mAs) were compared with low-dose (tube current was 50 mAs or 30 mAs). Results: Low-dosage helical CT scan provides excellent images. In 100 chest medical checkup, 39 nodules or masses were revealed, enlarged lymph node was noted in 1 case; emphysema or bullae was demonstrated in 3 segments; thickening of bronchial wall was shown in 2 cases; and localized pleural thickening was found in 1 case. Conclusion: In chest checkup or lung cancer screening low-dosage helical CT (tube current 30 mAs) will not only guarantee image quality but also reduce the radiation dose during the examination. (authors)

An experience of qualified preventive screening: shiraz smart screening software.

Science.gov (United States)

Islami Parkoohi, Parisa; Zare, Hashem; Abdollahifard, Gholamreza

2015-01-01

Computerized preventive screening software is a cost effective intervention tool to address non-communicable chronic diseases. Shiraz Smart Screening Software (SSSS) was developed as an innovative tool for qualified screening. It allows simultaneous smart screening of several high-burden chronic diseases and supports reminder notification functionality. The extent in which SSSS affects screening quality is also described. Following software development, preventive screening and annual health examinations of 261 school staff (Medical School of Shiraz, Iran) was carried out in a software-assisted manner. To evaluate the quality of the software-assisted screening, we used quasi-experimental study design and determined coverage, irregular attendance and inappropriateness proportions in relation with the manual and software-assisted screening as well as the corresponding number of requested tests. In manual screening method, 27% of employees were covered (with 94% irregular attendance) while by software-assisted screening, the coverage proportion was 79% (attendance status will clear after the specified time). The frequency of inappropriate screening test requests, before the software implementation, was 41.37% for fasting plasma glucose, 41.37% for lipid profile, 0.84% for occult blood, 0.19% for flexible sigmoidoscopy/colonoscopy, 35.29% for Pap smear, 19.20% for mammography and 11.2% for prostate specific antigen. All of the above were corrected by the software application. In total, 366 manual screening and 334 software-assisted screening tests were requested. SSSS is an innovative tool to improve the quality of preventive screening plans in terms of increased screening coverage, reduction in inappropriateness and the total number of requested tests.

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

Science.gov (United States)

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

2009-01-01

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

Mobile applications for handheld devices to screen and randomize acute stroke patients in clinical trials.

Science.gov (United States)

Qureshi, Ai; Connelly, B; Abbott, Ei; Maland, E; Kim, J; Blake, J

2012-08-01

The availability of internet connectivity and mobile application software used by low-power handheld devices makes smart phones of unique value in time-sensitive clinical trials. Trial-specific applications can be downloaded by investigators from various mobile software distribution platforms or web applications delivered over HTTP. The Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) II investigators in collaboration with MentorMate released the ATACH-II Patient Recruitment mobile application available on iPhone, Android, and Blackberry in 2011. The mobile application provides tools for pre-screening, assessment of eligibility, and randomization of patients. Since the release of ATACH-II mobile application, the CLEAR-IVH (Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage) trial investigators have also adopted such a mobile application. The video-conferencing capabilities of the most recent mobile devices open up additional opportunities to involve central coordinating centers in the recruitment process in real time.

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

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

2017-05-31

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

76 FR 23817 - Statement of Organization, Functions, and Delegations of Authority; National Institutes of Health

Science.gov (United States)

2011-04-28

... and approaches to allow an integrated assessment of high throughput screening endpoints and... development contracts, cooperative agreements, and other support mechanisms. Biomolecular Screening Branch (N V52, formerly HN V52). (1) Develops research and testing activities in high and medium throughput...

Development and Implementation of a Smartphone Application to Promote Physical Activity and Reduce Screen-Time in Adolescent Boys

OpenAIRE

Lubans, David R.; Smith, Jordan J.; Skinner, Geoff; Morgan, Philip J.

2014-01-01

Purpose: The primary aim is to describe the development and implementation of a smartphone application (app) designed to promote physical activity and reduce screen-time in adolescent boys ‘at risk’ of obesity from low-income communities.Methods: An app was developed to support the delivery of a face-to-face school-based obesity prevention program known as the ‘Active Teen Leaders Avoiding Screen-time’ (ATLAS) program. ATLAS was guided by self-determination theory and social cognitive theory ...

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.

Fast Enrichment Screening for Safeguards Applications

International Nuclear Information System (INIS)

Simpson, A.; McElhaney, S.

2010-01-01

Methods for rapid non-destructive uranium enrichment classification of large containers are of importance to safeguards and counter-terrorism agencies. There is a need to quickly categorize and segregate suspect items as 'depleted' or 'enriched' on a 'Go/No Go' basis. Recent improvements in gamma spectroscopy technologies have provided the capability to perform rapid field analysis using portable and hand-held devices such as battery-operated medium and high resolution detectors (including lanthanum halide and high purity germanium). Furthermore a new generation of portal monitors are currently under development with advanced spectroscopic capabilities. Instruments and technologies that were previously the domain of complex lab systems are now widely available as touch-screen 'off-the-shelf' units. Despite such advances, the task of enrichment analysis remains a complex exercise. This is particularly so when surveying large items such as drums and crates containing debris of unknown density and composition contaminated with uranium. The challenge is equally applicable to safeguards inspectors evaluating large items and for interdiction of illicit special nuclear materials in mass transport e.g. shipping containers at ports and borders. The variable shielding, container size, lack of matrix knowledge, wall thickness and self-shielding compound this problem. Performing an accurate assessment within the short count time window demanded of the field operative, leads to the need for a reliable method that can adapt to such conditions and is robust to a wide dynamic range of counting statistics. Several methods are evaluated with reference to the performance metrics defined in applicable standards. The primary issue is to minimize the bias that can result from attenuation effects, particularly as the gamma emissions from U235 are low energy and therefore highly susceptible to absorption in large containers with metal scrap. Use of other radiometric signatures such as

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

OpenAIRE

Henry Heberle

2014-01-01

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

Affinity selection-mass spectrometry and its emerging application to the high throughput screening of G protein-coupled receptors.

Science.gov (United States)

Whitehurst, Charles E; Annis, D Allen

2008-07-01

Advances in combinatorial chemistry and genomics have inspired the development of novel affinity selection-based screening techniques that rely on mass spectrometry to identify compounds that preferentially bind to a protein target. Of the many affinity selection-mass spectrometry techniques so far documented, only a few solution-based implementations that separate target-ligand complexes away from unbound ligands persist today as routine high throughput screening platforms. Because affinity selection-mass spectrometry techniques do not rely on radioactive or fluorescent reporters or enzyme activities, they can complement traditional biochemical and cell-based screening assays and enable scientists to screen targets that may not be easily amenable to other methods. In addition, by employing mass spectrometry for ligand detection, these techniques enable high throughput screening of massive library collections of pooled compound mixtures, vastly increasing the chemical space that a target can encounter during screening. Of all drug targets, G protein coupled receptors yield the highest percentage of therapeutically effective drugs. In this manuscript, we present the emerging application of affinity selection-mass spectrometry to the high throughput screening of G protein coupled receptors. We also review how affinity selection-mass spectrometry can be used as an analytical tool to guide receptor purification, and further used after screening to characterize target-ligand binding interactions, enabling the classification of orthosteric and allosteric binders.

Toward standardizing and reporting colorectal cancer screening indicators on an international level: The International Colorectal Cancer Screening Network

NARCIS (Netherlands)

Benson, Victoria S.; Atkin, Wendy S.; Green, Jane; Nadel, Marion R.; Patnick, Julietta; Smith, Robert A.; Villain, Patricia; Patnick, J.; Atkin, W. S.; Altenhofen, L.; Ancelle-Park, R.; Benson, V. S.; Green, J.; Levin, T. R.; Moss, S. M.; Nadel, M.; Ransohoff, D.; Segnan, N.; Smith, R. A.; Villain, P.; Weller, D.; Koukari, A.; Young, G.; López-Kostner, F.; Antoljak, N.; Suchánek, S.; Zavoral, M.; Holten, I.; Malila, N.; Salines, E.; Brenner, G.; Herszényi, L.; Tulassay, Z.; Rennert, G.; Senore, C.; Zappa, M.; Zorzi, M.; Saito, H.; Leja, M.; Dekker, E.; Jansen, J.; Hol, L.; Kuipers, E.; Kaminski, M. F.; Regula, J.; Sfarti, C.; Trifan, A.; Tang, C.-L.; Hrcka, R.; Binefa, G.; Espinàs, J. A.; Peris, M.; Chen, T. H.; Steele, R.; Pou, G.; Bisges, D.; Dwyer, D.; Groves, C.; Courteau, S.; Kramer, R.; Siegenthaler, K.; Lane, D.; Herrera, C.; Rogers, J.; Rojewski, M.; Wolf, Holly; Sung, J. J.; Ling, K.; Bryant, H.; Rabeneck, L.; Dale, J.; Sware, L.; Yang, H.; Viguier, J.; Von Karsa, L.; Kupcinskas, L.; Deutekom, M.; Törnberg, S.; Austoker, J.; Beral, V.; Monk, C.; Valori, R.; Watson, J.; Kobrin, S.; Pignone, M.; Taplin, S.

2012-01-01

The International Colorectal Cancer Screening Network was established in 2003 to promote best practice in the delivery of organized colorectal cancer screening programs. To facilitate evaluation of such programs, we defined a set of universally applicable colorectal cancer screening measures and

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

KAUST Repository

Sobhy, M. A.

2011-11-07

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

Printable Electrochemical Biosensors: A Focus on Screen-Printed Electrodes and Their Application

Directory of Open Access Journals (Sweden)

Keiichiro Yamanaka

2016-10-01

Full Text Available In this review we present electrochemical biosensor developments, focusing on screen-printed electrodes (SPEs and their applications. In particular, we discuss how SPEs enable simple integration, and the portability needed for on-field applications. First, we briefly discuss the general concept of biosensors and quickly move on to electrochemical biosensors. Drawing from research undertaken in this area, we cover the development of electrochemical DNA biosensors in great detail. Through specific examples, we describe the fabrication and surface modification of printed electrodes for sensitive and selective detection of targeted DNA sequences, as well as integration with reverse transcription-polymerase chain reaction (RT-PCR. For a more rounded approach, we also touch on electrochemical immunosensors and enzyme-based biosensors. Last, we present some electrochemical devices specifically developed for use with SPEs, including USB-powered compact mini potentiostat. The coupling demonstrates the practical use of printable electrode technologies for application at point-of-use. Although tremendous advances have indeed been made in this area, a few challenges remain. One of the main challenges is application of these technologies for on-field analysis, which involves complicated sample matrices.

New generation expandable sand screens

OpenAIRE

Syltøy, Christer

2014-01-01

Master's thesis in Petroleum engineering This thesis aims to give a general insight into sand control and various sorts of sand control measures and applications of sand control tools. Special focus will be given to expandable sand screens – a technology which came about in the late 1990’s through the use of flexible, expandable tubulars as base pipe in sand screens. More specifically Darcy’s Hydraulic Endurance Screens, a compliant sand screen system using hydraulic activation, and the fu...

Immobilization Techniques for Microarray: Challenges and Applications

Directory of Open Access Journals (Sweden)

Satish Balasaheb Nimse

2014-11-01

Full Text Available The highly programmable positioning of molecules (biomolecules, nanoparticles, nanobeads, nanocomposites materials on surfaces has potential applications in the fields of biosensors, biomolecular electronics, and nanodevices. However, the conventional techniques including self-assembled monolayers fail to position the molecules on the nanometer scale to produce highly organized monolayers on the surface. The present article elaborates different techniques for the immobilization of the biomolecules on the surface to produce microarrays and their diagnostic applications. The advantages and the drawbacks of various methods are compared. This article also sheds light on the applications of the different technologies for the detection and discrimination of viral/bacterial genotypes and the detection of the biomarkers. A brief survey with 115 references covering the last 10 years on the biological applications of microarrays in various fields is also provided.

New intensifying screens in clinical radiology. Pt. 2

International Nuclear Information System (INIS)

Freyschmidt, J.; Saure, D.; Hagemann, G.

1976-01-01

A clinically applicable procedure for testing new intensifying rare earth screens, as well as the special Siemens' screen is described. The results are related to universal screeens. The film-screen combination α 4XD (gadolinium oxysulphide with normal, green sensitive film) results in a reduction of radiation dose to half with detail comparable with universal screens. The Siemens' special screen has similar advantages. Screens with a higher intensification factor and reduction of the mAs to one sixth results in loss of detail. This does not necessarily reduce their clinical use if they are used for appropriate purposes. The results of this clinically orientated technique agreed well with physically objective methods using lead grids. The advantages of the new screens are discussed in terms of their practical application. (orig.) [de

Screening for novel laccase-producing microbes.

Science.gov (United States)

Kiiskinen, L-L; Rättö, M; Kruus, K

2004-01-01

To discover novel laccases potential for industrial applications. Fungi were cultivated on solid media containing indicator compounds that enabled the detection of laccases as specific colour reactions. The indicators used were Remazol Brilliant Blue R (RBBR), Poly R-478, guaiacol and tannic acid. The screening work resulted in isolation of 26 positive fungal strains. Liquid cultivations of positive strains confirmed that four efficient laccase producers were found in the screening. Biochemical characteristics of the four novel laccases were typical for fungal laccases in terms of molecular weight, pH optima and pI. The laccases showed good thermal stability at 60 degrees C. Plate-test screening based on polymeric dye compounds, guaiacol and tannic acid is an efficient way to discover novel laccase producers. The results indicated that screening for laccase activity can be performed with guaiacol and RBBR or Poly R-478. Laccases have many potential industrial applications including textile dye decolourization, delignification of pulp and effluent detoxification. It is essential to find novel, efficient enzymes to further develop these applications. This study showed that relatively simple plate test screening method can be used for discovery of novel laccases. Copyright 2004 The Society for Applied Microbiology

Fabrication and characterization of pixelated Gd{sub 2}O{sub 2}S:Tb scintillator screens for digital X-ray imaging applications

Energy Technology Data Exchange (ETDEWEB)

Kim, Jongyul, E-mail: kjongyul@kaist.ac.kr [Korea Advanced Institute of Science and Technology, 335 Gwahangno, Daejeon 305-701 (Korea, Republic of); Kyoung Cha, Bo; Hyung Bae, Jun; Lee, Chae-hun; Kim, Hyungtaek; Chang, Sungho; Cho, Gyuseong [Korea Advanced Institute of Science and Technology, 335 Gwahangno, Daejeon 305-701 (Korea, Republic of); Sim, Cheulmuu; Kim, Taejoo [Korea Atomic Energy Research Institute, 150 Deokjin-dong, Daejeon 305-353 (Korea, Republic of)

2011-05-15

X-ray imaging detectors in combination with scintillator screens have been widely used in digital X-ray imaging applications. Gd{sub 2}O{sub 2}S:Tb was used as scintillation material for pixelated scintillator screens based on silicon substrates (wafer) with a micropore array of various dimensions fabricated using the photolithography and deep reactive ion etching (DRIE) process. The relative light output and the modulation transfer function (MTF) of each fabricated scintillator screen were measured by a cooled CCD and compared with those of Lanex screens. The spatial resolution of our scintillator screens was higher but their light outputs were lower than those of Lanex screen probably due to the loss of light at the wall surfaces. Therefore further treatment of the wall surface, such as reflective coating, seems necessary to compensate the light loss.

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

Directory of Open Access Journals (Sweden)

Noji Hiroyuki

2009-01-01

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

Application of First Trimester Screening in the Prognostication of Small for Gestational Age

Directory of Open Access Journals (Sweden)

Reza Saeidi

2018-05-01

Full Text Available Background: Fetal growth restriction is defined as the failure of the fetus to achieve its full growth potential. The present study aimed to investigate the application of first trimester screening in the prediction of small for gestational age (SGA.Methods: This cohort study was conducted on the consecutive and unselected women with singleton pregnancies undergoing routine first-trimester examinations in a health center affiliated to Neyshabur University of Medical Sciences in Razavi Khorasan Iran during February 2014-March 2016. Subjects received a first-trimester visit by a physician, which included the entry of basic maternal characteristics, medical history, measurement of maternal weight and height, ultrasound examination for fetal anatomy, and measurement of crown-rump length to assess gestational age.Results: SGA was significantly correlated with maternal age, parity, and body mass index. Furthermore, a significant association was observed between SGA and smoking habits in the mothers.Conclusion: According to the results, first trimester screening was a useful method for the prediction of SGA.

Application of neural networks to waste site screening

Energy Technology Data Exchange (ETDEWEB)

Dabiri, A.E.; Kraft, T.; Hilton, J.M. [Science Applications International Corp., San Diego, CA (United States)

1993-03-01

Waste site screening requires knowledge of the actual concentrations of hazardous materials and rates of flow around and below the site with time. The present approach to site screening consists primarily of drilling, boreholes near contaminated site and chemically analyzing the extracted physical samples and processing the data. In addition, hydraulic and geochemical soil properties are obtained so that numerical simulation models can be used to interpret and extrapolate the field data. The objective of this work is to investigate the feasibility of using neural network techniques to reduce the cost of waste site screening. A successful technique may lead to an ability to reduce the number of boreholes and the number of samples analyzed from each borehole to properly screen the waste site. The analytic tool development described here is inexpensive because it makes use of neural network techniques that can interpolate rapidly and which can learn how to analyze data rather than having to be explicitly programmed. In the following sections, data collection and data analyses will be described, followed by a section on different neural network techniques used. The results will be presented and compared with mathematical model. Finally, the last section will summarize the research work performed and make several recommendations for future work.

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

Science.gov (United States)

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

2011-06-28

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

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

Directory of Open Access Journals (Sweden)

Katherina Petrou

2018-03-01

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

Feature Screening for Ultrahigh Dimensional Categorical Data with Applications.

Science.gov (United States)

Huang, Danyang; Li, Runze; Wang, Hansheng

2014-01-01

Ultrahigh dimensional data with both categorical responses and categorical covariates are frequently encountered in the analysis of big data, for which feature screening has become an indispensable statistical tool. We propose a Pearson chi-square based feature screening procedure for categorical response with ultrahigh dimensional categorical covariates. The proposed procedure can be directly applied for detection of important interaction effects. We further show that the proposed procedure possesses screening consistency property in the terminology of Fan and Lv (2008). We investigate the finite sample performance of the proposed procedure by Monte Carlo simulation studies, and illustrate the proposed method by two empirical datasets.

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.

Assessment of critical minerals: Updated application of an early-warning screening methodology

Science.gov (United States)

McCullough, Erin A.; Nassar, Nedal

2017-01-01

Increasing reliance on non-renewable mineral resources reinforces the need for identifying potential supply constraints before they occur. The US National Science and Technology Council recently released a report that outlines a methodology for screening potentially critical minerals based on three indicators: supply risk (R), production growth (G), and market dynamics (M). This early-warning screening was initially applied to 78 minerals across the years 1996 to 2013 and identified a subset of minerals as “potentially critical” based on the geometric average of these indicators—designated as criticality potential (C). In this study, the screening methodology has been updated to include data for 2014, as well as to incorporate revisions and modifications to the data, where applicable. Overall, C declined in 2014 for the majority of minerals examined largely due to decreases in production concentration and price volatility. However, the results vary considerably across minerals, with some minerals, such as gallium, recording increases for all three indicators. In addition to assessing magnitudinal changes, this analysis also examines the significance of the change relative to historical variation for each mineral. For example, although mined nickel’s R declined modestly in 2014 in comparison to that of other minerals, it was by far the largest annual change recorded for mined nickel across all years examined and is attributable to Indonesia’s ban on the export of unprocessed minerals. Based on the 2014 results, 20 minerals with the highest C values have been identified for further study including the rare earths, gallium, germanium, rhodium, tantalum, and tungsten.

Screening from the epidemiological point of view

International Nuclear Information System (INIS)

Becker, N.

2002-01-01

The scope of screening is to identify disease in a clinically inapparent stage in order to treat more effectively. However, the required application of a test to large subsets of the population implies risks which cannot be ignored. Thus, the introduction of a test for use in screening without previously established evidence of a benefit which exceeds potential harm by far cannot be justified. With regard to cancer, evidence of effectiveness has been proven for screening on cervical (Papsmear), breast (mammography) and colorectal (faecal occult blood test) cancer. The routine application of a screening procedure which has been proven effective provides the benefit in terms of mortality reduction seen in the trials only if the entire screening chain, from the test over potentially required assessment to treatment, is offered with highest quality and is under permanent quality control. (orig.) [de

78 FR 76860 - Contraband Screening for Criminal Justice Applications

Science.gov (United States)

2013-12-19

... for the detection of contraband. Screening technology is widely used by criminal justice practitioners...: 1. Model Number and Name of the screening system/device. 2. Technology used by the system/device for... container or bag), Plastic, Wood, Ceramic, Powder (in a small packet), and/or Paper (e.g., folded currency...

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

Science.gov (United States)

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

2017-11-26

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

Application of Shape Similarity in Pose Selection and Virtual Screening in CSARdock2014 Exercise.

Science.gov (United States)

Kumar, Ashutosh; Zhang, Kam Y J

2016-06-27

To evaluate the applicability of shape similarity in docking-based pose selection and virtual screening, we participated in the CSARdock2014 benchmark exercise for identifying the correct docking pose of inhibitors targeting factor XA, spleen tyrosine kinase, and tRNA methyltransferase. This exercise provides a valuable opportunity for researchers to test their docking programs, methods, and protocols in a blind testing environment. In the CSARdock2014 benchmark exercise, we have implemented an approach that uses ligand 3D shape similarity to facilitate docking-based pose selection and virtual screening. We showed here that ligand 3D shape similarity between bound poses could be used to identify the native-like pose from an ensemble of docking-generated poses. Our method correctly identified the native pose as the top-ranking pose for 73% of test cases in a blind testing environment. Moreover, the pose selection results also revealed an excellent correlation between ligand 3D shape similarity scores and RMSD to X-ray crystal structure ligand. In the virtual screening exercise, the average RMSD for our pose prediction was found to be 1.02 Å, and it was one of the top performances achieved in CSARdock2014 benchmark exercise. Furthermore, the inclusion of shape similarity improved virtual screening performance of docking-based scoring and ranking. The coefficient of determination (r(2)) between experimental activities and docking scores for 276 spleen tyrosine kinase inhibitors was found to be 0.365 but reached 0.614 when the ligand 3D shape similarity was included.

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.

Balancing Fairness and Efficiency: The Impact of Identity-Blind and Identity-Conscious Accountability on Applicant Screening

Science.gov (United States)

Self, William T.; Mitchell, Gregory; Mellers, Barbara A.; Tetlock, Philip E.; Hildreth, J. Angus D.

2015-01-01

This study compared two forms of accountability that can be used to promote diversity and fairness in personnel selections: identity-conscious accountability (holding decision makers accountable for which groups are selected) versus identity-blind accountability (holding decision makers accountable for making fair selections). In a simulated application screening process, undergraduate participants (majority female) sorted applicants under conditions of identity-conscious accountability, identity-blind accountability, or no accountability for an applicant pool in which white males either did or did not have a human capital advantage. Under identity-conscious accountability, participants exhibited pro-female and pro-minority bias, particularly in the white-male-advantage applicant pool. Under identity-blind accountability, participants exhibited no biases and candidate qualifications dominated interview recommendations. Participants exhibited greater resentment toward management under identity-conscious accountability. PMID:26660723

Selection and Specification of Rear-Projection Screens.

Science.gov (United States)

Vlahos, Petro

1961-01-01

The characteristics of the rear-projection screen are examined in detail. Numerical constants are provided that define these characteristics for practical screens and convert foot-candles to footlamberts. A procedure is given by which an optimum screen may be specified for a specific application. Contents include--(1) introduction, (2) projection…

Hazard screening application guide. Safety Analysis Report Update Program

Energy Technology Data Exchange (ETDEWEB)

None

1992-06-01

The basic purpose of hazard screening is to group precesses, facilities, and proposed modifications according to the magnitude of their hazards so as to determine the need for and extent of follow on safety analysis. A hazard is defined as a material, energy source, or operation that has the potential to cause injury or illness in human beings. The purpose of this document is to give guidance and provide standard methods for performing hazard screening. Hazard screening is applied to new and existing facilities and processes as well as to proposed modifications to existing facilities and processes. The hazard screening process evaluates an identified hazards in terms of the effects on people, both on-site and off-site. The process uses bounding analyses with no credit given for mitigation of an accident with the exception of certain containers meeting DOT specifications. The process is restricted to human safety issues only. Environmental effects are addressed by the environmental program. Interfaces with environmental organizations will be established in order to share information.

Application of PET and PET/CT imaging for cancer screening

International Nuclear Information System (INIS)

Chen Yenkung; Hu Fenglan; Shen Yehyou; Liao, A.C.; Hung, T.Z.; Su, Chentau; Chen Liangkuang

2004-01-01

The aim of this study was to evaluate the potential application of 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) and PET/CT for cancer screening in asymptomatic individuals. Methods: The subjects consisted of 3631 physical check up examinees (1947 men, 1684 women; mean age ±SD, 52.1±8.2 y) with non-specific medical histories. Whole-body FDG PET (or PET/CT), ultrasound and tumor markers were performed on all patients. Focal hypermetabolic areas with intensities equal to or exceeding the level of FDG uptake in the brain and bladder were considered abnormal and interpreted as neoplasia. Follow-up periods were longer than one year. Results: Among the 3631 FDG PET (including 1687 PET/CT), ultrasound and tumor markers examinations, malignant tumors were discovered in 47 examinees (1.29%). PET findings were true-positive in 38 of the 47 cancers (80.9%). In addition, 32 of the 47 cancers were performed with the PET-CT scan. PET detected cancer lesions in 28 of the 32 examinees. However, the CT detected cancer lesions in only 15 of 32 examinees. Conclusion: The sensitivity of FDG PET in the detection of a wide variety of cancers is high. Most cancer can be detected with FDG PET in a resectable stage. CT of the PET/CT for localization and characteristics of the lesion shows an increased specificity of the PET scan. Using ultrasound and tumor markers may complement the PET scan in cancer screening for hepatic and urologic neoplasms. (authors)

Hierarchical virtual screening approaches in small molecule drug discovery.

Science.gov (United States)

Kumar, Ashutosh; Zhang, Kam Y J

2015-01-01

Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery. Copyright © 2014 Elsevier Inc. All rights reserved.

Practical application of in silico fragmentation based residue screening with ion mobility high-resolution mass spectrometry.

Science.gov (United States)

Kaufmann, Anton; Butcher, Patrick; Maden, Kathry; Walker, Stephan; Widmer, Mirjam

2017-07-15

A screening concept for residues in complex matrices based on liquid chromatography coupled to ion mobility high-resolution mass spectrometry LC/IMS-HRMS is presented. The comprehensive four-dimensional data (chromatographic retention time, drift time, mass-to-charge and ion abundance) obtained in data-independent acquisition (DIA) mode was used for data mining. An in silico fragmenter utilizing a molecular structure database was used for suspect screening, instead of targeted screening with reference substances. The utilized data-independent acquisition mode relies on the MS E concept; where two constantly alternating HRMS scans (low and high fragmentation energy) are acquired. Peak deconvolution and drift time alignment of ions from the low (precursor ion) and high (product ion) energy scan result in relatively clean product ion spectra. A bond dissociation in silico fragmenter (MassFragment) supplied with mol files of compounds of interest was used to explain the observed product ions of each extracted candidate component (chromatographic peak). Two complex matrices (fish and bovine liver extract) were fortified with 98 veterinary drugs. Out of 98 screened compounds 94 could be detected with the in silico based screening approach. The high correlation among drift time and m/z value of equally charged ions was utilized for an orthogonal filtration (ranking). Such an orthogonal ion mobility based filter removes multiply charged ions (e.g. peptides and proteins from the matrix) as well as noise and artefacts. Most significantly, this filtration dramatically reduces false positive findings but hardly increases false negative findings. The proposed screening approach may offer new possibilities for applications where reference compounds are hardly or not at all commercially available. Such areas may be the analysis of metabolites of drugs, pyrrolizidine alkaloids, marine toxins, derivatives of sildenafil or novel designer drugs (new psychoactive substances

Cathode material for lithium ion accumulators prepared by screen printing for Smart Textile applications

Science.gov (United States)

Syrový, T.; Kazda, T.; Syrová, L.; Vondrák, J.; Kubáč, L.; Sedlaříková, M.

2016-03-01

The presented study is focused on the development of LiFePO4 based cathode for thin and flexible screen printed secondary lithium based accumulators. An ink formulation was developed for the screen printing technique, which enabled mass production of accumulator's cathode for Smart Label and Smart Textile applications. The screen printed cathode was compared with an electrode prepared by the bar coating technique using an ink formulation based on the standard approach of ink composition. Obtained LiFePO4 cathode layers were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS) and galvanostatic charge/discharge measurements at different loads. The discharge capacity, capacity retention and stability at a high C rate of the LiFePO4 cathode were improved when Super P and PVDF were replaced by conductive polymers PEDOT:PSS. The achieved capacity during cycling at various C rates was approximately the same at the beginning and at the end, and it was about 151 mAh/g for cycling under 1C. The obtained results of this novelty electrode layer exceed the parameters of several electrode layers based on LiFePO4 published in literature in terms of capacity, cycling stability and overcomes them in terms of simplicity/industrial process ability of cathode layer fabrication and electrode material preparation.

Providing floating capabilities in latest-generation sand screens

Energy Technology Data Exchange (ETDEWEB)

Bowen, E.G.; Coronado, M.P. [Society of Petroleum Engineers, Richardson, TX (United States)]|[Baker Hughes, Houston, TX (United States)

2008-10-15

Alternative production methods are needed for the massive reserves located in the bitumen region of Canada's tar sands. The area has over 100 installations of sand screens/slotted liners in both injection and production legs using steam-assisted gravity drainage (SAGD) technology. Multiple wells must be drilled from a single pad because of the sensitive nature of the environment. With significant depths of these wells, a floating sand screen provides assurance that the sand screen will reach the desired depth. Paraffin is generally used to plug the flow access of the screen during installation. This paper discussed a new technology that has been developed to allow for sand screen installations without relying on paraffin wax to withstand differential pressure. The new technology uses a hydro-mechanical valving system incorporated into the screen design to temporarily close off the screen while being run in the hole. The paper described how the technology could provide a reliable, time-saving solution for SAGD installations when floating sand control screens are needed. The paper discussed current technology and its limitations, sand screen installation, screen design for floating applications, and additional applications. It was concluded that this technology solution provides a unique alternative to the methods currently used to install sand screens with SAGD technology in the fast growing Canadian market for bitumen recovery. 2 refs., 5 figs.

High-throughput screening (HTS) and modeling of the retinoid ...

Science.gov (United States)

Presentation at the Retinoids Review 2nd workshop in Brussels, Belgium on the application of high throughput screening and model to the retinoid system Presentation at the Retinoids Review 2nd workshop in Brussels, Belgium on the application of high throughput screening and model to the retinoid system

"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.

Virtual screening applications: a study of ligand-based methods and different structure representations in four different scenarios.

Science.gov (United States)

Hristozov, Dimitar P; Oprea, Tudor I; Gasteiger, Johann

2007-01-01

Four different ligand-based virtual screening scenarios are studied: (1) prioritizing compounds for subsequent high-throughput screening (HTS); (2) selecting a predefined (small) number of potentially active compounds from a large chemical database; (3) assessing the probability that a given structure will exhibit a given activity; (4) selecting the most active structure(s) for a biological assay. Each of the four scenarios is exemplified by performing retrospective ligand-based virtual screening for eight different biological targets using two large databases--MDDR and WOMBAT. A comparison between the chemical spaces covered by these two databases is presented. The performance of two techniques for ligand--based virtual screening--similarity search with subsequent data fusion (SSDF) and novelty detection with Self-Organizing Maps (ndSOM) is investigated. Three different structure representations--2,048-dimensional Daylight fingerprints, topological autocorrelation weighted by atomic physicochemical properties (sigma electronegativity, polarizability, partial charge, and identity) and radial distribution functions weighted by the same atomic physicochemical properties--are compared. Both methods were found applicable in scenario one. The similarity search was found to perform slightly better in scenario two while the SOM novelty detection is preferred in scenario three. No method/descriptor combination achieved significant success in scenario four.

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Application of Adverse Outcome Pathways to U.S. EPA's Endocrine Disruptor Screening Program.

Science.gov (United States)

Browne, Patience; Noyes, Pamela D; Casey, Warren M; Dix, David J

2017-09-01

The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. This review describes the EDSP's use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. Pathway frameworks can facilitate a weight of evidence determination of a chemical's potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304.

Caribbean marine biodiversity as a source of new compounds of biomedical interest and others industrial applications

OpenAIRE

Nuñez, R.; Garateix, A.; Laguna, A.; Fernández, M.D.; Ortiz, E.; Llanio, M.; Valdés, O.; Rodríguez, A.; Menéndez, R.

2006-01-01

The Cuban marine flora and fauna is characterized by its richness in species that represents an extraordinary natural source of unexplored biomolecular diversity. Many of those biomolecules could represent important tools for industrial applications. For this reason, in our Centre the main aim was focused on the isolation, purification and characterization of bioactive compounds present in marine invertebrates with particular emphasis on sponges, cnidarians, seaweeds and marine...

The Nonmydriatic Fundus Camera in Diabetic Retinopathy Screening: A Cost-Effective Study with Evaluation for Future Large-Scale Application

Directory of Open Access Journals (Sweden)

Giuseppe Scarpa

2016-01-01

Full Text Available Aims. The study aimed to present the experience of a screening programme for early detection of diabetic retinopathy (DR using a nonmydriatic fundus camera, evaluating the feasibility in terms of validity, resources absorption, and future advantages of a potential application, in an Italian local health authority. Methods. Diabetic patients living in the town of Ponzano, Veneto Region (Northern Italy, were invited to be enrolled in the screening programme. The “no prevention strategy” with the inclusion of the estimation of blindness related costs was compared with screening costs in order to evaluate a future extensive and feasible implementation of the procedure, through a budget impact approach. Results. Out of 498 diabetic patients eligible, 80% was enrolled in the screening programme. 115 patients (34% were referred to an ophthalmologist and 9 cases required prompt treatment for either proliferative DR or macular edema. Based on the pilot data, it emerged that an extensive use of the investigated screening programme, within the Greater Treviso area, could prevent 6 cases of blindness every year, resulting in a saving of €271,543.32 (−13.71%. Conclusions. Fundus images obtained with a nonmydriatic fundus camera could be considered an effective, cost-sparing, and feasible screening tool for the early detection of DR, preventing blindness as a result of diabetes.

Application of health behavior theories to breast cancer screening among Asian women.

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Ahmadian, Maryam; Samah, Asnarulkhadi Abu

2013-01-01

Although breast cancer is a major public health worry among Asian women, adherence to screening for the disease remains an obstacle to its prevention. A variety of psycho-social and cultural factors predispose women to delay or avoidance of screening for breast cancer symptoms at the early stages when cure is most likely to be successful. Yet few interventions implemented to date to address this condition in this region have drawn on health behavior theory. This paper reviews the existing literature on several cognitive theories and models associated with breast cancer screening, with an emphasis on the work that has been done in relation to Asian women. To conduct this review, a number of electronic databases were searched with context-appropriate inclusion criteria. Little empirical work was found that specifically addressed the applicability of health theories in promoting adherence to the current breast cancer prevention programs Among Asian women. However, a few studies were found that addressed individual cognitive factors that are likely to encourage women's motivation to protect themselves against breast cancer in this region of the world. The findings suggest that multi-level, socio-cultural interventions that focus on cognitive factors have much promise with this issue. Interventions are needed that effectively and efficiently target the personal motivation of at-risk Asian women to seek out and engage in breast cancer prevention. Concerning implications, personal motivation to seek out and engage in individual preventive actions for breast cancer prevention among Asian women is a timely, high priority target with practical implications for community development and health promotion. Further studies using qualitative, anthropologic approaches shaped for implementation in multi-ethnic Asian settings are needed to inform and guide these interventions.

Development and application of a general plasmid reference material for GMO screening.

Science.gov (United States)

Wu, Yuhua; Li, Jun; Wang, Yulei; Li, Xiaofei; Li, Yunjing; Zhu, Li; Li, Jun; Wu, Gang

The use of analytical controls is essential when performing GMO detection through screening tests. Additionally, the presence of taxon-specific sequences is analyzed mostly for quality control during GMO detection. In this study, 11 commonly used genetic elements involving three promoters (P-35S, P-FMV35S and P-NOS), four marker genes (Bar, NPTII, HPT and Pmi), and four terminators (T-NOS, T-35S, T-g7 and T-e9), together with the reference gene fragments from six major crops of maize, soybean, rapeseed, rice, cotton and wheat, were co-integrated into the same single plasmid to construct a general reference plasmid pBI121-Screening. The suitability test of pBI121-Screening plasmid as reference material indicated that the non-target sequence on the pBI121-Screening plasmid did not affect the PCR amplification efficiencies of screening methods and taxon-specific methods. The sensitivity of screening and taxon-specific assays ranged from 5 to 10 copies of pBI121-Screening plasmid, meeting the sensitivity requirement of GMO detection. The construction of pBI121-Screening solves the lack of a general positive control for screening tests, thereby reducing the workload and cost of preparing a plurality of the positive control. Copyright © 2016 Elsevier B.V. All rights reserved.

[New intensifying screens in clinical radiology. II. Examinations in clinical practice].

Science.gov (United States)

Freyschmidt, J; Saure, D; Hagemann, G

1976-09-01

A clinically applicable procedure for testing new intensifying rare earth screens, as well as the special Siemens' screen is described. The results are related to universal screens. The film-screen combination alpha 4XD (gadolinium oxysulphide with normal, green sensitive film) results in a reduction of radiation dose to half with detail comparable with universal screens. The Siemens' special screen has similar advantages. Screens with a higher intensification factor and reduction of the mAs to one sixth results in loss of detail. This does not necessarily reduce their clinical use if they are used for appropriate purposes. The results of this clinically orientated technique agreed well with physically objective methods using lead grids. The advantages of the new screens are discussed in terms of their practical application.

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.

Organic-resistant screen-printed graphitic electrodes: Application to on-site monitoring of liquid fuels

International Nuclear Information System (INIS)

Almeida, Eduardo S.; Silva, Luiz A.J.; Sousa, Raquel M.F.; Richter, Eduardo M.; Foster, Christopher W.; Banks, Craig E.; Munoz, Rodrigo A.A.

2016-01-01

This work presents the potential application of organic-resistant screen-printed graphitic electrodes (SPGEs) for fuel analysis. The required analysis of the antioxidant 2,6-di-tert-butylphenol (2,6-DTBP) in biodiesel and jet fuel is demonstrated as a proof-of-concept. The screen-printing of graphite, Ag/AgCl and insulator inks on a polyester substrate (250 μm thickness) resulted in SPGEs highly compatible with liquid fuels. SPGEs were placed on a batch-injection analysis (BIA) cell, which was filled with a hydroethanolic solution containing 99% v/v ethanol and 0.1 mol L −1 HClO 4 (electrolyte). An electronic micropipette was connected to the cell to perform injections (100 μL) of sample or standard solutions. Over 200 injections can be injected continuously without replacing electrolyte and SPGE strip. Amperometric detection (+1.1 V vs. Ag/AgCl) of 2,6-DTBP provided fast (around 8 s) and precise (RSD = 0.7%, n = 12) determinations using an external calibration curve. The method was applied for the analysis of biodiesel and aviation jet fuel samples and comparable results with liquid and gas chromatographic analyses, typically required for biodiesel and jet fuel samples, were obtained. Hence, these SPGE strips are completely compatible with organic samples and their combination with the BIA cell shows great promise for routine and portable analysis of fuels and other organic liquid samples without requiring sophisticated sample treatments. - Highlights: • Organic-resistant screen-printed graphitic electrodes (SPGE) for (bio)fuels. • Screen-printing of conductive and insulator inks on thin polyester substrate. • Continuous detection of antioxidants in electrolyte with 99% v/v ethanol. • SPGE coupled with batch-injection analysis allows over 200 injections (100 μL). • Similar results to GC and HPLC analyses of biodiesel and aviation jet fuels.

Vibrational spectroscopy in diagnosis and screening

CERN Document Server

Severcan, F

2012-01-01

In recent years there has been a tremendous growth in the use of vibrational spectroscopic methods for diagnosis and screening. These applications range from diagnosis of disease states in humans, such as cancer, to rapid identification and screening of microorganisms. The growth in such types of studies has been possible thanks to advances in instrumentation and associated computational and mathematical tools for data processing and analysis. This volume of Advances in Biomedical Spectroscopy contains chapters from leading experts who discuss the latest advances in the application of Fourier

Automated microscopy for high-content RNAi screening

Science.gov (United States)

2010-01-01

Fluorescence microscopy is one of the most powerful tools to investigate complex cellular processes such as cell division, cell motility, or intracellular trafficking. The availability of RNA interference (RNAi) technology and automated microscopy has opened the possibility to perform cellular imaging in functional genomics and other large-scale applications. Although imaging often dramatically increases the content of a screening assay, it poses new challenges to achieve accurate quantitative annotation and therefore needs to be carefully adjusted to the specific needs of individual screening applications. In this review, we discuss principles of assay design, large-scale RNAi, microscope automation, and computational data analysis. We highlight strategies for imaging-based RNAi screening adapted to different library and assay designs. PMID:20176920

Applications of self-organizing neural networks in virtual screening and diversity selection.

Science.gov (United States)

Selzer, Paul; Ertl, Peter

2006-01-01

Artificial neural networks provide a powerful technique for the analysis and modeling of nonlinear relationships between molecular structures and pharmacological activity. Many network types, including Kohonen and counterpropagation, also provide an intuitive method for the visual assessment of correspondence between the input and output data. This work shows how a combination of neural networks and radial distribution function molecular descriptors can be applied in various areas of industrial pharmaceutical research. These applications include the prediction of biological activity, the selection of screening candidates (cherry picking), and the extraction of representative subsets from large compound collections such as combinatorial libraries. The methods described have also been implemented as an easy-to-use Web tool, allowing chemists to perform interactive neural network experiments on the Novartis intranet.

Prenatal Screening Using Maternal Markers

Directory of Open Access Journals (Sweden)

Howard Cuckle

2014-05-01

Full Text Available Maternal markers are widely used to screen for fetal neural tube defects (NTDs, chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening.

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

Directory of Open Access Journals (Sweden)

Yoshiyuki Ogata

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

Effects of "Like Type" Sex Pairings between Applicants-Principals and Type of Focal Position Considered at the Screening Stage of the Selection Process

Science.gov (United States)

Young, I. Phillip

2005-01-01

This study addresses the screening decisions for a national random sample of high school principals as viewed from the attraction-similarity theory of interpersonal perceptions. Independent variables are the sex of principals, sex of applicants, and the type of focal positions sought by hypothetical job applicants (teacher or counselor). Dependent…

Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis

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Mads S. Bergholt

2017-12-01

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

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

Science.gov (United States)

Naujoks, Nicola; Stemmer, Andreas

2006-08-01

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

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

International Nuclear Information System (INIS)

Manil, B.

2007-11-01

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

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

International Nuclear Information System (INIS)

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

2009-07-01

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

High-throughput molecular binding analysis on open-microfluidic platform

OpenAIRE

Pan, Yuchen

2016-01-01

Biomolecular binding interactions underpin life sciences tools that are essential to fields as diverse as molecular biology and clinical chemistry. Merging needs in life science research entail fast, robust and quantitative binding reaction characterization, such as antibody selection, gene regulation screening and drug screening. Identification, characterization, and optimization of these diverse molecular binding reactions demands the availability of powerful, quantitative analytical tools....

Virtual screening of compound libraries.

Science.gov (United States)

Cerqueira, Nuno M F S A; Sousa, Sérgio F; Fernandes, Pedro A; Ramos, Maria João

2009-01-01

During the last decade, Virtual Screening (VS) has definitively established itself as an important part of the drug discovery and development process. VS involves the selection of likely drug candidates from large libraries of chemical structures by using computational methodologies, but the generic definition of VS encompasses many different methodologies. This chapter provides an introduction to the field by reviewing a variety of important aspects, including the different types of virtual screening methods, and the several steps required for a successful virtual screening campaign within a state-of-the-art approach, from target selection to postfilter application. This analysis is further complemented with a small collection important VS success stories.

Intensifying screens in transaxial tomography

International Nuclear Information System (INIS)

Debelder, M.H.; Bollen, R.H.

1981-01-01

This patent claim by Agfa-Gevaert relates to a method for the production of transaxial tomographs, a combination of materials therefor and X-ray intensifying screens incorporating at least one reflecting element for use in transaxial tomography, wherein the exposure of a photographic silver halide emulsion material proceeds at an angle within the range of 2 0 to 10 0 in conjunction with an X-ray fluorescent intensifying screen including an ultra-violet and/or visible radiation reflective coating or sheet to increase the radiation output of the screen and to reduce the exposure time and radiation dose e.g. in medical X-ray applications. (author)

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

Directory of Open Access Journals (Sweden)

Alexander Gust

2014-09-01

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

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

Science.gov (United States)

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

2017-03-01

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

Development of wall thinning screening system and its application to a commercial nuclear power plant

International Nuclear Information System (INIS)

Ryu, Kyung Ha; Hwang, Il Soon; Kim, Ji Hyun

2013-01-01

Highlights: • Wall loss screening system (WalSS) has been developed based on ES-DCPD method. • Screening criteria was established based on the thinning of the actual shape that occur in the power plant. • With the criteria, the WalSS gives priority of the need for inspection. • This technique was successfully applied to commercial nuclear power plant. - Abstract: A new non-destructive evaluation (NDE) method has been developed for metal pipes for the detection wall thinning. The method has been showed to be suitable for applications to electric power generation plants where flow accelerated corrosion (FAC) of carbon steel piping is a significant cause of increased maintenance and plant personnel casualty. The wall thinning screening system (WalSS) was developed in two major phases. In the first phase, the equipotential switching direct current potential drop (ES-DCPD) method was developed for piping wall (Ryu et al., 2008a, 2010). In the second phase, in this paper, a quantitative detection criteria was developed. The relative ES-DCPD change of 3.8% has been defined as the screening criteria for wall thinning schematization. This criteria means that the component with measured ES-DCPD change greater than 3.8% is called for a more comprehensive examination. In the criteria development, all variables were taken into consideration based on commercial plant piping inspection data such as initial thickness distributions, wall thinning shape and nominal thickness. The developed WalSS based on ES-DCPD was applied to a moisture separator reheater (MSR) drain line of a commercial nuclear power plant (NPP) during a scheduled overhaul. The measured ES-DCPD change was 2.16%, which is lower than the ES-DCPD criteria, identifying the pipe having adequate wall thickness. This is confirmed by site thickness inspection using ultrasonic technique (UT)

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

Science.gov (United States)

Bronstein, Leo; Koeppl, Heinz

2018-01-01

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

Retinopathy of prematurity screening criteria in Iran: new screening guidelines.

Science.gov (United States)

Roohipoor, Ramak; Karkhaneh, Reza; Farahani, Afsar; Ebrahimiadib, Nazanin; Modjtahedi, Bobeck; Fotouhi, Akbar; Yaseri, Mehdi; Khodabande, Alireza; Zarei, Mohammad; Imani Fuladi, Marjan; Taheri, Arash; Riazi Esfahani, Mohammad; Loewenstein, John

2016-07-01

To test the applicability of existing retinopathy of prematurity (ROP) guidelines on Iranian patients and to develop novel ROP screening criteria in Iran. Both eyes of 1932 infants born ≤37 weeks of gestation and/or weighting ≤3000 g were included in this prospective cohort study that was conducted across nine neonatal intensive care units and a tertiary eye hospital ROP clinic. The patients were examined for ROP and the need for treatment (type 1 ROP or worse). All the patients were screened 4 weeks after birth or at 31 weeks of postmenstrual age, whichever was later. The patients were followed until retinal vascularisation was completed or the patients reached 50 weeks of gestational age (GA) without prethreshold ROP. A receiver operating characteristic curve was used to determine the best screening criteria for ROP. Screening criteria from other countries were applied to our patient data to determine their ability to appropriately detect ROP. Patients with ROP requiring treatment. The mean GA±SD and birth weight (BW)±SD of the screened patients were 32±2.7 weeks and 1713±516 g, respectively. Using criteria of GA≤32 weeks or BW ≤2000 yielded sensitivity and specificity of 100% and 26.7%, respectively, for treatment requiring ROP regardless of clinical comorbidities. Using screening recommendations of American Academy of Pediatrics would miss 25.4% of ROP and 8.4%ROP requiring treatment in our cohort. Other countries screening recommendations would result in a significant amount of missed cases of treatment requiring ROP when applied to Iran. As a result, we have proposed new guidelines for premature babies in Iran. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Organic-resistant screen-printed graphitic electrodes: Application to on-site monitoring of liquid fuels

Energy Technology Data Exchange (ETDEWEB)

Almeida, Eduardo S.; Silva, Luiz A.J.; Sousa, Raquel M.F.; Richter, Eduardo M. [Universidade Federal de Uberlândia, Universidade Federal de Uberlândia, Av. João Naves de Ávila, 2121, Uberlândia, MG, 38408100 (Brazil); Foster, Christopher W.; Banks, Craig E. [Manchester Metropolitan University, Faculty of Science and the Environment, School of Science and the Environment, Division of Chemistry and Environmental Science, Manchester, M1 5GD, England (United Kingdom); Munoz, Rodrigo A.A., E-mail: raamunoz@iqufu.ufu.br [Universidade Federal de Uberlândia, Universidade Federal de Uberlândia, Av. João Naves de Ávila, 2121, Uberlândia, MG, 38408100 (Brazil)

2016-08-31

This work presents the potential application of organic-resistant screen-printed graphitic electrodes (SPGEs) for fuel analysis. The required analysis of the antioxidant 2,6-di-tert-butylphenol (2,6-DTBP) in biodiesel and jet fuel is demonstrated as a proof-of-concept. The screen-printing of graphite, Ag/AgCl and insulator inks on a polyester substrate (250 μm thickness) resulted in SPGEs highly compatible with liquid fuels. SPGEs were placed on a batch-injection analysis (BIA) cell, which was filled with a hydroethanolic solution containing 99% v/v ethanol and 0.1 mol L{sup −1} HClO{sub 4} (electrolyte). An electronic micropipette was connected to the cell to perform injections (100 μL) of sample or standard solutions. Over 200 injections can be injected continuously without replacing electrolyte and SPGE strip. Amperometric detection (+1.1 V vs. Ag/AgCl) of 2,6-DTBP provided fast (around 8 s) and precise (RSD = 0.7%, n = 12) determinations using an external calibration curve. The method was applied for the analysis of biodiesel and aviation jet fuel samples and comparable results with liquid and gas chromatographic analyses, typically required for biodiesel and jet fuel samples, were obtained. Hence, these SPGE strips are completely compatible with organic samples and their combination with the BIA cell shows great promise for routine and portable analysis of fuels and other organic liquid samples without requiring sophisticated sample treatments. - Highlights: • Organic-resistant screen-printed graphitic electrodes (SPGE) for (bio)fuels. • Screen-printing of conductive and insulator inks on thin polyester substrate. • Continuous detection of antioxidants in electrolyte with 99% v/v ethanol. • SPGE coupled with batch-injection analysis allows over 200 injections (100 μL). • Similar results to GC and HPLC analyses of biodiesel and aviation jet fuels.

QSAR Methods to Screen Endocrine Disruptors

Directory of Open Access Journals (Sweden)

Nicola Porta

2016-08-01

Full Text Available The identification of endocrine disrupting chemicals (EDCs is one of the important goals of environmental chemical hazard screening. We report on in silico methods addressing toxicological studies about EDCs with a special focus on the application of QSAR models for screening purpose. Since Estrogen-like (ER activity has been extensively studied, the majority of the available models are based on ER-related endpoints. Some of these models are here reviewed and described. As example for their application, we screen an assembled dataset of candidate substitutes for some known EDCs belonging to the chemical classes of phthalates, bisphenols and parabens, selected considering their toxicological relevance and broad application, with the general aim of preliminary assessing their ED potential. The goal of the substitution processes is to advance inherently safer chemicals and products, consistent with the principles of green chemistry. Results suggest that the integration of a family of different models accounting for different endpoints can be a convenient way to describe ED as properly as possible and allow also both to increase the confidence of the predictions and to maximize the probability that most active compounds are correctly found.

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

The design of light pipe with microstructures for touch screen

Science.gov (United States)

Yang, Bo; Lu, Kan; Liu, Pengfei; Wei, Xiaona

2010-11-01

Touch screen has a very wide range of applications. Most of them are used in public information inquiries, for instance, service inquiries in telecommunication bureau, tax bureau, bank system, electric department, etc...Touch screen can also be used for entertainment and virtual reality applications too. Traditionally, touch screen was composed of pairs of infrared LED and correspondent receivers which were all installed in the screen frame. Arrays of LED were set in the adjacent sides of the frame of an infrared touch screen while arrays of the infrared receivers were fixed in each opposite side, so that the infrared detecting network was formed. While the infrared touch screen has some technical limitations nowadays such as the low resolution, limitations of touching methods and fault response due to environmental disturbances. The plastic material has a relatively high absorption rate for infrared light, which greatly limits the size of the touch screen. Our design uses laser diode as source and change the traditional inner structure of touch screen by using a light pipe with microstructures. The geometric parameters of the light pipe and the microstructures were obtained through equation solving. Simulation results prove that the design method for touch screen proposed in this paper could achieve high resolution and large size of touch screen.

Nafion® modified-screen printed gold electrodes and their carbon nanostructuration for electrochemical sensors applications.

Science.gov (United States)

García-González, Raquel; Fernández-Abedul, M Teresa; Costa-García, Agustín

2013-03-30

Screen printed electrodes are frequently used in electroanalytical applications because of their properties such as small size, low detection limit, fast response time, high reproducibility and disposable nature. On the other hand, since the discovery of carbon nanotubes there has been enormous interest in exploring and exploiting their properties, especially for their use in chemical (bio)sensors and nanoscale electronic devices. This paper reports the characterization of gold screen printed electrodes, modified with Nafion(®) and nanostructured with carbon nanotubes and carbon nanofibers dispersed on Nafion(®). The dispersing agent and the nanostructure have a marked effect on the analytical signal that, in turn depends on the intrinsic characteristics of the analyte. Several model analytes have been employed in this study. Anionic, cationic and neutral species such as methylene blue, dopamine, iron (III) sulfate, potassium ferrycianide and urea were considered. The importance for the development of nanostructured sensors relies on the fact that depending on these factors the situation may vary from a notorious enhancement of the signal to a blocking or even decrease. Copyright © 2013 Elsevier B.V. All rights reserved.

DG-AMMOS: a new tool to generate 3d conformation of small molecules using distance geometry and automated molecular mechanics optimization for in silico screening.

Science.gov (United States)

Lagorce, David; Pencheva, Tania; Villoutreix, Bruno O; Miteva, Maria A

2009-11-13

Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

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.

Solid-state NMR spectroscopy on complex biomolecules

NARCIS (Netherlands)

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

2010-01-01

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

Effects of the application of ankle functional rehabilitation exercise on the ankle joint functional movement screen and isokinetic muscular function in patients with chronic ankle sprain.

Science.gov (United States)

Ju, Sung-Bum; Park, Gi Duck

2017-02-01

[Purpose] This study was conducted to investigate the effects of ankle functional rehabilitation exercise on ankle joint functional movement screen results and isokinetic muscular function in patients with chronic ankle sprain patients. [Subjects and Methods] In this study, 16 patients with chronic ankle sprain were randomized to an ankle functional rehabilitation exercise group (n=8) and a control group (n=8). The ankle functional rehabilitation exercise centered on a proprioceptive sense exercise program, which was applied 12 times for 2 weeks. To verify changes after the application, ankle joint functional movement screen scores and isokinetic muscular function were measured and analyzed. [Results] The ankle functional rehabilitation exercise group showed significant improvements in all items of the ankle joint functional movement screen and in isokinetic muscular function after the exercise, whereas the control group showed no difference after the application. [Conclusion] The ankle functional rehabilitation exercise program can be effectively applied in patients with chronic ankle sprain for the improvement of ankle joint functional movement screen score and isokinetic muscular function.

Current status and application of fine screening technology in China

Science.gov (United States)

Chernova, E. V.; Chernov, D. V.

2017-10-01

The paper presents data on the design and technical parameters of high frequency vibrating screens, which are produced by Chinese manufacturer - company Landsky Tech Ltd. The technology of high frequency vibration is widely used at mining and metallurgical industries to separate fine and ultra-fine particles from the flow of dry material or pulp. The paper contains different types of screening systems, description, advantages and disadvantages of equipment and test results from mineral processing plants.

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.

Revisions of the Fish Invasiveness Screening Kit (FISK) for its application in warmer climatic zones, with particular reference to peninsular Florida.

Science.gov (United States)

Lawson, Larry L; Hill, Jeffrey E; Vilizzi, Lorenzo; Hardin, Scott; Copp, Gordon H

2013-08-01

The initial version (v1) of the Fish Invasiveness Scoring Kit (FISK) was adapted from the Weed Risk Assessment of Pheloung, Williams, and Halloy to assess the potential invasiveness of nonnative freshwater fishes in the United Kingdom. Published applications of FISK v1 have been primarily in temperate-zone countries (Belgium, Belarus, and Japan), so the specificity of this screening tool to that climatic zone was not noted until attempts were made to apply it in peninsular Florida. To remedy this shortcoming, the questions and guidance notes of FISK v1 were reviewed and revised to improve clarity and extend its applicability to broader climatic regions, resulting in changes to 36 of the 49 questions. In addition, upgrades were made to the software architecture of FISK to improve overall computational speed as well as graphical user interface flexibility and friendliness. We demonstrate the process of screening a fish species using FISK v2 in a realistic management scenario by assessing the Barcoo grunter Scortum barcoo (Terapontidae), a species whose management concerns are related to its potential use for aquaponics in Florida. The FISK v2 screening of Barcoo grunter placed the species into the lower range of medium risk (score = 5), suggesting it is a permissible species for use in Florida under current nonnative species regulations. Screening of the Barcoo grunter illustrates the usefulness of FISK v2 as a proactive tool serving to inform risk management decisions, but the low level of confidence associated with the assessment highlighted a dearth of critical information on this species. © 2012 Society for Risk Analysis.

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

Science.gov (United States)

Chiang, Howard Hsueh-hao

2009-01-01

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

Smartphone-based audiometric test for screening hearing loss in the elderly.

Science.gov (United States)

Abu-Ghanem, Sara; Handzel, Ophir; Ness, Lior; Ben-Artzi-Blima, Miri; Fait-Ghelbendorf, Karin; Himmelfarb, Mordechai

2016-02-01

Hearing loss is widespread among the elderly. One of the main obstacles to rehabilitation is identifying individuals with potentially correctable hearing loss. Smartphone-based hearing tests can be administered at home, thus greatly facilitating access to screening. This study evaluates the use of a smartphone application as a screening tool for hearing loss in individuals aged ≥ 65 years. Twenty-six subjects aged 84.4 ± 6.73 years (mean ± SD) were recruited. Pure-tone audiometry was administered by both a smartphone application (uHear for iPhone, v1.0 Unitron, Canada) and a standard portable audiometer by trained personnel. Participants also completed a questionnaire on their hearing. Pure-tone thresholds were compared between the two testing modalities and correlated with the questionnaire results. The cutoff point for failing screening tests was a pure tone average of 40 dB for the frequencies 250-6,000 Hz. The smartphone application's pure tone thresholds were higher (poorer hearing) than the audiometric thresholds, with a significant difference in all frequencies but 2,000 Hz. The application and the audiometric values were in agreement for 24 subjects (92 %). The application had a sensitivity of 100 % and specificity of 60 % for screening compared with the audiometer. The questionnaire was significantly less accurate, having assigned a passing score to three participants who failed both the application and audiometric tests. While a smartphone application may not be able to accurately determine the level of hearing impairment, it is useful as a highly accessible portable audiometer substitute for screening for hearing loss in elderly populations.

Intelligent Screening Systems for Cervical Cancer

Directory of Open Access Journals (Sweden)

Yessi Jusman

2014-01-01

Full Text Available Advent of medical image digitalization leads to image processing and computer-aided diagnosis systems in numerous clinical applications. These technologies could be used to automatically diagnose patient or serve as second opinion to pathologists. This paper briefly reviews cervical screening techniques, advantages, and disadvantages. The digital data of the screening techniques are used as data for the computer screening system as replaced in the expert analysis. Four stages of the computer system are enhancement, features extraction, feature selection, and classification reviewed in detail. The computer system based on cytology data and electromagnetic spectra data achieved better accuracy than other data.

Clinical comparison of high-speed rare-earth screen and par-speed screen for diagnostic efficacy and radiation dosage

International Nuclear Information System (INIS)

Robinson, T.; Becker, J.A.; Olson, A.P.

1982-01-01

One hundred patients underwent excretory urography and a comparison was made of ten-minute, well-collimated images that were obtained with both par-speed and rare-earth screens, the latter being 6.5 times faster than the par-speed calcium tungstate screens. Radiation dose was greatly reduced with the rare-earth screens. There were fewer inferior examinations, even though fine detail was imaged poorly, and there was a slightly increased quantum mottle, which was only a minor problem at this low 65 kVp. Since quantum mottle increases with kVp, however, our results are not applicable to higher kVp examinations. Despite reduced detail and increased mottle, the overall image quality obtained with the rare-earth screen was superior to the image quality obtained with the par-speed screen

Automated screening for retinopathy

Directory of Open Access Journals (Sweden)

A. S. Rodin

2014-07-01

Full Text Available Retinal pathology is a common cause of an irreversible decrease of central vision commonly found amongst senior population. Detection of the earliest signs of retinal diseases can be facilitated by viewing retinal images available from the telemedicine networks. To facilitate the process of retinal images, screening software applications based on image recognition technology are currently on the various stages of development.Purpose: To develop and implement computerized image recognition software that can be used as a decision support technologyfor retinal image screening for various types of retinopathies.Methods: The software application for the retina image recognition has been developed using C++ language. It was tested on dataset of 70 images with various types of pathological features (age related macular degeneration, chorioretinitis, central serous chorioretinopathy and diabetic retinopathy.Results: It was shown that the system can achieve a sensitivity of 73 % and specificity of 72 %.Conclusion: Automated detection of macular lesions using proposed software can significantly reduce manual grading workflow. In addition, automated detection of retinal lesions can be implemented as a clinical decision support system for telemedicine screening. It is anticipated that further development of this technology can become a part of diagnostic image analysis system for the electronic health records.

HealthNavigator: a mobile application for chronic disease screening and linkage to services at an urban Primary Health Network.

Science.gov (United States)

Seneviratne, Martin G; Hersch, Fred; Peiris, David P

2018-03-26

Mobile applications (apps) are promising tools to support chronic disease screening and linkage to health services. They have the potential to increase healthcare access for vulnerable populations. The HealthNavigator app was developed to provide chronic disease risk assessments, linkage to local general practitioners (GPs) and lifestyle programs, and a personalised health report for discussion with a GP. Assessments were either self-administered or facilitated by community health workers through a Primary Health Network (PHN) initiative targeting ethnically diverse communities. In total, 1492 assessments (80.4% self-administered, 19.6% facilitated) were conducted over a 12-month period in Queensland, Australia. Of these, 26% of people screened came from postcodes representing the lowest quartile of socioeconomic disadvantage. When compared against self-administered assessments, subjects screened by the facilitated program were more likely to be born outside Australia (80.5 v. 33.2%, P<0.001), and to fall within a high risk category based on cardiovascular risk scores (19.8 v. 13.7%, P<0.01) and type 2 diabetes mellitus risk scores (58.0 v. 40.1%, P<0.001). Mobile apps embedded into PHN programs may be a useful adjunct for the implementation of community screening programs. Further research is needed to determine their effect on health service access and health outcomes.

PET in cancer screening: a controversial imaging

International Nuclear Information System (INIS)

Su Minggang; Tan Tianzhi

2012-01-01

Malignancy has been one of the most dangerous threats to human health. Early diagnosis and treatment are key factors for improving prognosis. Cancer screening is an important way to detect early stage cancer and precancerous lesion. PET has been used increasingly in cancer screening in accordance with the requirement of the public. Though a great number of data show that PET can find some subclinical malignancy, yet as a cancer screening modality, PET is still controversial in contemporary medical practice. The aim of this article is to review the application status and existing problem of PET in cancer screening, and to offer some recognition and view about cancer srceening. (authors)

Inkjet and screen printing for electronic applications

OpenAIRE

Medina Rodríguez, Beatriz

2016-01-01

Printed electronics (PE) is a set of printing methods used to create electrical devices on various substrates. Printing typically uses common printing equipment suitable for defining patterns on material, such as screen printing, flexography, gravure, offset lithography, and inkjet. Electrically functional, electronic or optical inks are deposited on the substrate, creating active or passive devices. PE offers a great advantage when compared to traditional processes or microelectronics du...

The urgent need for universally applicable simple screening procedures and diagnostic criteria for gestational diabetes mellitus – lessons from projects funded by the World Diabetes Foundation

Directory of Open Access Journals (Sweden)

Maximilian de Courten

2012-07-01

Full Text Available Background: To address the risks of adverse pregnancy outcomes and future type 2 diabetes associated with gestational diabetes mellitus (GDM, its early detection and timely treatment is essential. In the absence of an international consensus, multiple different guidelines on screening and diagnosis of GDM have existed for a long time. This may be changing with the publication of the recommendations by the International Association of Diabetes and Pregnancy Study Groups. However, none of these guidelines take into account evidence from or ground realities of resource-poor settings. Objective: This study aimed to investigate whether GDM projects supported by the World Diabetes Foundation in developing countries utilize any of the internationally recommended guidelines for screening and diagnosis of GDM, explore experiences on applicability and usefulness of the guidelines and barriers if any, in implementing the guidelines. These projects have reached out to thousands of pregnant women through capacity building and improvement of access to GDM screening and diagnosis in the developing world and therefore provide a rich field experience on the applicability of the guidelines in resource-poor settings. Design: A mixed methods approach using questionnaires and interviews was utilised to review 11 GDM projects. Two projects were conducted by the same partner; interviews were conducted in person or via phone by the first author with nine project partners and one responded via email. The interviews were analysed using content analysis. Results: The projects use seven different screening procedures and diagnostic criteria and many do not completely adhere to one guideline alone. Various challenges in adhering to the recommendations emerged in the interviews, including problems with screening women during the recommended time period, applicability of some of the listed risk factors used for (pre-screening, difficulties with reaching women for testing in

Screening applicants for risk of poor academic performance: a novel scoring system using preadmission grade point averages and graduate record examination scores.

Science.gov (United States)

Luce, David

2011-01-01

The purpose of this study was to develop an effective screening tool for identifying physician assistant (PA) program applicants at highest risk for poor academic performance. Prior to reviewing applications for the class of 2009, a retrospective analysis of preadmission data took place for the classes of 2006, 2007, and 2008. A single composite score was calculated for each student who matriculated (number of subjects, N=228) incorporating the total undergraduate grade point average (UGPA), the science GPA (SGPA), and the three component Graduate Record Examination (GRE) scores: verbal (GRE-V), quantitative (GRE-Q), analytical (GRE-A). Individual applicant scores for each of the five parameters were ranked in descending quintiles. Each applicant's five quintile scores were then added, yielding a total quintile score ranging from 25, which indicated an excellent performance, to 5, which indicated poorer performance. Thirteen of the 228 students had academic difficulty (dismissal, suspension, or one-quarter on academic warning or probation). Twelve of the 13 students having academic difficulty had a preadmission total quintile score 12 (range, 6-14). In response to this descriptive analysis, when selecting applicants for the class of 2009, the admissions committee used the total quintile score for screening applicants for interviews. Analysis of correlations in preadmission, graduate, and postgraduate performance data for the classes of 2009-2013 will continue and may help identify those applicants at risk for academic difficulty. Establishing a threshold total quintile score of applicant GPA and GRE scores may significantly decrease the number of entering PA students at risk for poor academic performance.

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

International Nuclear Information System (INIS)

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

2016-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-11-01

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

Photoactivated bioconjugation between ortho-azidophenols and anilines: a facile approach to biomolecular photopatterning.

Science.gov (United States)

El Muslemany, Kareem M; Twite, Amy A; ElSohly, Adel M; Obermeyer, Allie C; Mathies, Richard A; Francis, Matthew B

2014-09-10

Methods for the surface patterning of small molecules and biomolecules can yield useful platforms for drug screening, synthetic biology applications, diagnostics, and the immobilization of live cells. However, new techniques are needed to achieve the ease, feature sizes, reliability, and patterning speed necessary for widespread adoption. Herein, we report an easily accessible and operationally simple photoinitiated reaction that can achieve patterned bioconjugation in a highly chemoselective manner. The reaction involves the photolysis of 2-azidophenols to generate iminoquinone intermediates that couple rapidly to aniline groups. We demonstrate the broad functional group compatibility of this reaction for the modification of proteins, polymers, oligonucleotides, peptides, and small molecules. As a specific application, the reaction was adapted for the photolithographic patterning of azidophenol DNA on aniline glass substrates. The presence of the DNA was confirmed by the ability of the surface to capture living cells bearing the sequence complement on their cell walls or cytoplasmic membranes. Compared to other light-based DNA patterning methods, this reaction offers higher speed and does not require the use of a photoresist or other blocking material.

Machine Learning-based Virtual Screening and Its Applications to Alzheimer's Drug Discovery: A Review.

Science.gov (United States)

Carpenter, Kristy A; Huang, Xudong

2018-06-07

Virtual Screening (VS) has emerged as an important tool in the drug development process, as it conducts efficient in silico searches over millions of compounds, ultimately increasing yields of potential drug leads. As a subset of Artificial Intelligence (AI), Machine Learning (ML) is a powerful way of conducting VS for drug leads. ML for VS generally involves assembling a filtered training set of compounds, comprised of known actives and inactives. After training the model, it is validated and, if sufficiently accurate, used on previously unseen databases to screen for novel compounds with desired drug target binding activity. The study aims to review ML-based methods used for VS and applications to Alzheimer's disease (AD) drug discovery. To update the current knowledge on ML for VS, we review thorough backgrounds, explanations, and VS applications of the following ML techniques: Naïve Bayes (NB), k-Nearest Neighbors (kNN), Support Vector Machines (SVM), Random Forests (RF), and Artificial Neural Networks (ANN). All techniques have found success in VS, but the future of VS is likely to lean more heavily toward the use of neural networks - and more specifically, Convolutional Neural Networks (CNN), which are a subset of ANN that utilize convolution. We additionally conceptualize a work flow for conducting ML-based VS for potential therapeutics of for AD, a complex neurodegenerative disease with no known cure and prevention. This both serves as an example of how to apply the concepts introduced earlier in the review and as a potential workflow for future implementation. Different ML techniques are powerful tools for VS, and they have advantages and disadvantages albeit. ML-based VS can be applied to AD drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Overview of guidelines on breast screening

DEFF Research Database (Denmark)

Juhl Jørgensen, Karsten; Kalager, Mette; Barratt, Alexandra

2017-01-01

Updated guidelines on breast cancer screening have been published by several major organisations over the past five years. Recommendations vary regarding both age range, screening interval, and even on whether breast screening should be offered at all. The variation between recommendations reflects....... The estimates vary according to the methodology of the randomised trials, and the design of the observational studies. Guideline recommendations reflect the choice of evidence informing them. While there are well-developed tools to deal with randomised trials in guideline work, these are not always used......, or they may not be followed as recommended. Further, results of trials performed decades ago may no longer be applicable. For observational studies, the framework for inclusion in guidelines is not similarly well-developed and there are methodological concerns specific to screening interventions...

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.

Imaging-Based Screen Identifies Laminin 411 as a Physiologically Relevant Niche Factor with Importance for i-Hep Applications

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John Ong

2018-03-01

Full Text Available Summary: Use of hepatocytes derived from induced pluripotent stem cells (i-Heps is limited by their functional differences in comparison with primary cells. Extracellular niche factors likely play a critical role in bridging this gap. Using image-based characterization (high content analysis; HCA of freshly isolated hepatocytes from 17 human donors, we devised and validated an algorithm (Hepatocyte Likeness Index; HLI for comparing the hepatic properties of cells against a physiological gold standard. The HLI was then applied in a targeted screen of extracellular niche factors to identify substrates driving i-Heps closer to the standard. Laminin 411, the top hit, was validated in two additional induced pluripotent stem cell (iPSC lines, primary tissue, and an in vitro model of α1-antitrypsin deficiency. Cumulatively, these data provide a reference method to control and screen for i-Hep differentiation, identify Laminin 411 as a key niche protein, and underscore the importance of combining substrates, soluble factors, and HCA when developing iPSC applications. : Rashid and colleagues demonstrate the utility of a high-throughput imaging platform for identification of physiologically relevant extracellular niche factors to advance i-Heps closer to their primary tissue counterparts. The extracellular matrix (ECM protein screen identified Laminin 411 as an important niche factor facilitating i-Hep-based disease modeling in vitro. Keywords: iPS hepatocytes, extracellular niche, image-based screening, disease modeling, laminin

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

Directory of Open Access Journals (Sweden)

Judiono J

2014-08-01

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

Applicability of Screening Tests for Oxytetracycline in the Milk of Three Breeds of Goats.

Science.gov (United States)

Attaie, Rahmat; Bsharat, Mohammed; Mora-Gutierrez, Adela

2016-06-01

Antibiotics are widely used in animal husbandry, and the presence of antibiotic residues in milk is a health hazard. The objectives of this study were to determine residual amounts of oxytetracycline in the milk of three breeds of goats using high-pressure liquid chromatography (HPLC) analysis and screening tests. It was also essential to explore the safe withdrawal period of oxytetracycline in lactating goats and examine the applicability of Charm ROSA and SNAP screening tests. The qualitative results of these tests were compared with the quantitative results of the HPLC method. Fifteen milking does, five each from the Alpine, LaMancha, and Nubian breeds, were selected from the herd at Prairie View A&M University. Milk samples containing antibiotic residues were deproteinized by HCl and acetonitrile, and then oxytetracycline was extracted from the supernatant. The residues of oxytetracycline in goat's milk up to 110 h after injection were qualitatively detected using the Charm ROSA test. Similarly, the SNAP test detected the antibiotic residues in milk up to 110 h after treatment. The HPLC results indicated that oxytetracycline residues in milk from Alpine goats were below the tolerance level (300 ng/ml) 82 h after drug treatment (72 h for LaManchas, 58 h for Nubians); however, the results of the screening tests would indicate longer withdrawal periods for milk from the breeds of goats studied, which would result in economic losses to goat's milk producers. The results of this study also indicated that oxytetracycline was not stable in raw goat's milk at refrigeration temperature or during pasteurization and that the concentrations decreased significantly. Commercial goat's milk is usually exposed to several hours of refrigeration and then to pasteurization. The results of this study indicated that, if oxytetracycline was present in raw goat's milk, the concentration would decrease significantly before it was marketed.

Effects of Application of Social Marketing Theory and the Health Belief Model in Promoting Cervical Cancer Screening among Targeted Women in Sisaket Province, Thailand.

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Wichachai, Suparp; Songserm, Nopparat; Akakul, Theerawut; Kuasiri, Chanapong

2016-01-01

Cervical cancer is a major public health problem in Thailand, being ranked second only to breast cancer. Thai women have been reported to have a low rate of cervical cancer screening (27.7% of the 80% goal of WHO). We therefore aimed to apply the social marketing theory and health belief model in promoting cervical cancer screening in Kanthararom District, Sisaket Province. A total of 92 from 974 targeted women aged 3060 years were randomly divided into two groups. The experimental group underwent application of social marketing theory and a health belief model program promoting cervical cancer screening while the control group received normal services. Two research tools were used: (1) application of social marketing theory and health belief model program and (2) questionnaire used to evaluate perceptions of cervical cancer. Descriptive and inferential statistics including paired sample ttest and independent ttest were used to analyze the data. After the program had been used, the mean score of perception of cervical cancer of experimental group was at a higher level (x=4.09; S.D. =0.30), than in the control group (x=3.82; S.D. =0.20) with statistical significance (psocial marketing and the health belief model be used to promote cervical cancer screening in targeted women and it can be promoted as a guideline for other health services, especially in health promotion and disease prevention.

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

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Mairet, Francis

2018-02-01

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

Cancer screening in patients infected with HIV.

Science.gov (United States)

Sigel, Keith; Dubrow, Robert; Silverberg, Michael; Crothers, Kristina; Braithwaite, Scott; Justice, Amy

2011-09-01

Non-AIDS-defining cancers are a rising health concern among HIV-infected patients. Cancer screening is now an important component of health maintenance in HIV clinical practice. The decision to screen an HIV-infected patient for cancer should include an assessment of individualized risk for the particular cancer, life expectancy, and the harms and benefits associated with the screening test and its potential outcome. HIV-infected patients are at enhanced risk of several cancers compared to the general population; anal cancer, hepatocellular carcinoma, Hodgkin's lymphoma, and lung cancer all have good evidence demonstrating an enhanced risk in HIV-infected persons. A number of cancer screening interventions have shown benefit for specific cancers in the general population, but data on the application of these tests to HIV-infected persons are limited. Here we review the epidemiology and background literature relating to cancer screening interventions in HIV-infected persons. We then use these data to inform a conceptual model for evaluating HIV-infected patients for cancer screening.

Discussion: Comparison of slope instability screening tools following a large storm event and application to forest management and policy

Science.gov (United States)

Lingley, Leslie; Slaughter, Stephen L.; Sarikhan, Isabelle Y.; Norman, David K.

2013-02-01

This discussion is in response to the article entitled "Comparison of slope stability screening tools following a large storm event and application to forest management and policy" by Kara Whittaker and Dan McShane (Geomorphology 145-146 (2012) 115-122). The discussion is coauthored by several geologists at the Washington Department of Natural Resources (WDNR) including those from the research and policy sections of the state agency.

Development and application of a universal Hemoplasma screening assay based on the SYBR green PCR principle.

Science.gov (United States)

Willi, Barbara; Meli, Marina L; Lüthy, Ruedi; Honegger, Hanspeter; Wengi, Nicole; Hoelzle, Ludwig E; Reusch, Claudia E; Lutz, Hans; Hofmann-Lehmann, Regina

2009-12-01

Hemotropic mycoplasmas (hemoplasmas) are the causative agents of infectious anemia in several mammalian species. Their zoonotic potential has recently been substantiated by the identification of a feline hemoplasma isolate in an immunocompromised human patient. Although species-specific diagnostic molecular methods have been developed, their application as screening tools is limited due to the species diversity of hemoplasmas. The goals of this study were to develop a universal hemoplasma screening assay with broad specificity based on the SYBR green PCR principle, to compare the assay with hemoplasma-specific TaqMan PCR, and to analyze potential tick vectors and human blood samples to address the zoonotic potential. The newly developed PCR assay based on the 16S rRNA gene amplified feline, canine, bovine, porcine, camelid, and murine hemoplasmas, as well as Mycoplasma penetrans and Mycoplasma pneumoniae. The lower detection limit for feline and canine hemoplasmas was 1 to 10 copies/PCR. The assay exhibited 98.2% diagnostic sensitivity and 92.1% diagnostic specificity for feline hemoplasmas. All 1,950 Ixodes ticks were PCR negative, suggesting that Ixodes ticks are not relevant vectors for the above-mentioned hemoplasma species in Switzerland. None of the 414 blood samples derived from anemic or immunocompromised human patients revealed a clear positive result. The SYBR green PCR assay described here is a suitable tool to screen for known and so-far-undiscovered hemoplasma species. Positive results should be confirmed by specific TaqMan PCR or sequencing.

DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening

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Villoutreix Bruno O

2009-11-01

Full Text Available Abstract Background Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Results Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. Conclusion DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

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

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

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

Patterned direct-write and screen-printing of NIR-to-visible upconverting inks for security applications.

Science.gov (United States)

Blumenthal, Tyler; Meruga, Jeevan; Stanley May, P; Kellar, Jon; Cross, William; Ankireddy, Krishnamraju; Vunnam, Swathi; Luu, Quocanh N

2012-05-11

Two methods of direct-write printing for producing highly resolved features of a polymer impregnated with luminescent upconversion phosphors for security applications are presented. The printed polymer structures range in shape from features to text. The thin polymer features were deposited by direct-write printing of atomized material as well as by screen-printing techniques. These films contain highly luminescent lanthanide-doped, rare-earth nanocrystals, β-NaYF₄:3%Er, 17%Yb, which are capped with oleic acid. This capping agent allows the nanocrystals to disperse throughout the films for full detailing of printed features. Upconversion of deposited features was obtained using a 980 nm wavelength laser with emission of upconverted light in the visible region at both 540 and 660 nm. Features were deposited onto high bond paper, Kapton®, and glass to demonstrate possible covert and forensic security printing applications, as they are printed in various features and invisible to 'naked-eye' viewing at low concentrations of nanocrystals.

Patterned direct-write and screen-printing of NIR-to-visible upconverting inks for security applications

International Nuclear Information System (INIS)

Blumenthal, Tyler; Meruga, Jeevan; Kellar, Jon; Cross, William; Ankireddy, Krishnamraju; Vunnam, Swathi; Stanley May, P; Luu, QuocAnh N

2012-01-01

Two methods of direct-write printing for producing highly resolved features of a polymer impregnated with luminescent upconversion phosphors for security applications are presented. The printed polymer structures range in shape from features to text. The thin polymer features were deposited by direct-write printing of atomized material as well as by screen-printing techniques. These films contain highly luminescent lanthanide-doped, rare-earth nanocrystals, β-NaYF 4 :3%Er, 17%Yb, which are capped with oleic acid. This capping agent allows the nanocrystals to disperse throughout the films for full detailing of printed features. Upconversion of deposited features was obtained using a 980 nm wavelength laser with emission of upconverted light in the visible region at both 540 and 660 nm. Features were deposited onto high bond paper, Kapton ® , and glass to demonstrate possible covert and forensic security printing applications, as they are printed in various features and invisible to ‘naked-eye’ viewing at low concentrations of nanocrystals. (paper)

Patterned direct-write and screen-printing of NIR-to-visible upconverting inks for security applications

Science.gov (United States)

Blumenthal, Tyler; Meruga, Jeevan; May, P. Stanley; Kellar, Jon; Cross, William; Ankireddy, Krishnamraju; Vunnam, Swathi; Luu, QuocAnh N.

2012-05-01

Two methods of direct-write printing for producing highly resolved features of a polymer impregnated with luminescent upconversion phosphors for security applications are presented. The printed polymer structures range in shape from features to text. The thin polymer features were deposited by direct-write printing of atomized material as well as by screen-printing techniques. These films contain highly luminescent lanthanide-doped, rare-earth nanocrystals, β-NaYF4:3%Er, 17%Yb, which are capped with oleic acid. This capping agent allows the nanocrystals to disperse throughout the films for full detailing of printed features. Upconversion of deposited features was obtained using a 980 nm wavelength laser with emission of upconverted light in the visible region at both 540 and 660 nm. Features were deposited onto high bond paper, Kapton®, and glass to demonstrate possible covert and forensic security printing applications, as they are printed in various features and invisible to ‘naked-eye’ viewing at low concentrations of nanocrystals.

Preliminary results from a novel CVD diamond detector system for molecular imaging applications

International Nuclear Information System (INIS)

Mahon, A.R.

1996-01-01

A novel biomolecular imaging system incorporating a Chemical Vapour Deposition diamond detector is in development. The synthetic diamond is used as a UV detector to image nucleic acids in electrophoresis gels. The microstrip diamond detector currently has a spatial resolution of 30 μm. Preliminary results are presented which include: QE measurements of diamond detectors, detector time response, detector UV response and current detection limits of biomolecules in gel. The potential applications of the technology, and its significant advantages in speed and sensitivity over the current systems are discussed

SEMIAUTOMATED SOLID-PHASE EXTRACTION PROCEDURE FOR DRUG SCREENING IN BIOLOGICAL-FLUIDS USING THE ASPEC SYSTEM IN COMBINATION WITH CLEAN SCREEN DAU COLUMNS

NARCIS (Netherlands)

CHEN, XH; FRANKE, JP; ENSING, K; WIJSBEEK, J; DEZEEUW, RA

1993-01-01

The use of a semi-automated solid-phase extraction system (ASPEC) for the screening of drugs in plasma and urine on a single mixed-mode column (Clean Screen DAU) is described. The processes of column preconditioning, sample application, column wash, pH adjustment and elution of the drugs were

Computer-Aided Solvent Screening for Biocatalysis

DEFF Research Database (Denmark)

Abildskov, Jens; Leeuwen, M.B. van; Boeriu, C.G.

2013-01-01

constrained properties related to chemical reaction equilibrium, substrate and product solubility, water solubility, boiling points, toxicity and others. Two examples are provided, covering the screening of solvents for lipase-catalyzed transesterification of octanol and inulin with vinyl laurate....... Esterification of acrylic acid with octanol is also addressed. Solvents are screened and candidates identified, confirming existing experimental results. Although the examples involve lipases, the method is quite general, so there seems to be no preclusion against application to other biocatalysts....

Screening length in dusty plasma crystals

International Nuclear Information System (INIS)

Nikolaev, V S; Timofeev, A V

2016-01-01

Particles interaction and value of the screening length in dusty plasma systems are of great interest in dusty plasma area. Three inter-particle potentials (Debye potential, Gurevich potential and interaction potential in the weakly collisional regime) are used to solve equilibrium equations for two dusty particles suspended in a parabolic trap. The inter-particle distance dependence on screening length, trap parameter and particle charge is obtained. The functional form of inter-particle distance dependence on ion temperature is investigated and compared with experimental data at 200-300 K in order to test used potentials applicability to dusty plasma systems at room temperatures. The preference is given to the Yukawa-type potential including effective values of particle charge and screening length. The estimated effective value of the screening length is 5-15 times larger than the Debye length. (paper)

Small Screen Use and Driving Safety.

Science.gov (United States)

Atchley, Paul; Strayer, David L

2017-11-01

The increased availability of "small screens," wireless devices with Internet-enabled connections, and their associated applications has almost overnight changed the way that we interact with our phones. The current work outlines some of the aspects of this problem as it relates to the influence of small screens on driving safety. Small screens are highly compelling to drivers, both for the information they convey and because the ability to ignore them while driving is impaired by cognitive resources used by the driving task itself. However, much is unknown about why people make choices to multitask while driving. Given the safety risks, it is recommended that parents, the public, and regulators take a stand against the use of Internet-enabled small screens unrelated to driving when the vehicle is in motion. Copyright © 2017 by the American Academy of Pediatrics.

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

Directory of Open Access Journals (Sweden)

Zheng Yang

2009-04-01

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

Iterative Cellular Screening System for Nanoparticle Safety Testing

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Franziska Sambale

2015-01-01

Full Text Available Nanoparticles have the potential to exhibit risks to human beings and to the environment; due to the wide applications of nanoproducts, extensive risk management must not be neglected. Therefore, we have constructed a cell-based, iterative screening system to examine a variety of nanoproducts concerning their toxicity during development. The sensitivity and application of various cell-based methods were discussed and proven by applying the screening to two different nanoparticles: zinc oxide and titanium dioxide nanoparticles. They were used as benchmarks to set up our methods and to examine their effects on mammalian cell lines. Different biological processes such as cell viability, gene expression of interleukin-8 and heat shock protein 70, as well as morphology changes were investigated. Within our screening system, both nanoparticle suspensions and coatings can be tested. Electric cell impedance measurements revealed to be a good method for online monitoring of cellular behavior. The implementation of three-dimensional cell culture is essential to better mimic in vivo conditions. In conclusion, our screening system is highly efficient, cost minimizing, and reduces the need for animal studies.

Compression force behaviours: An exploration of the beliefs and values influencing the application of breast compression during screening mammography

International Nuclear Information System (INIS)

Murphy, Fred; Nightingale, Julie; Hogg, Peter; Robinson, Leslie; Seddon, Doreen; Mackay, Stuart

2015-01-01

This research project investigated the compression behaviours of practitioners during screening mammography. The study sought to provide a qualitative understanding of ‘how’ and ‘why’ practitioners apply compression force. With a clear conflict in the existing literature and little scientific evidence base to support the reasoning behind the application of compression force, this research project investigated the application of compression using a phenomenological approach. Following ethical approval, six focus group interviews were conducted at six different breast screening centres in England. A sample of 41 practitioners were interviewed within the focus groups together with six one-to-one interviews of mammography educators or clinical placement co-ordinators. The findings revealed two broad humanistic and technological categories consisting of 10 themes. The themes included client empowerment, white-lies, time for interactions, uncertainty of own practice, culture, power, compression controls, digital technology, dose audit-safety nets, numerical scales. All of these themes were derived from 28 units of significant meaning (USM). The results demonstrate a wide variation in the application of compression force, thus offering a possible explanation for the difference between practitioner compression forces found in quantitative studies. Compression force was applied in many different ways due to individual practitioner experiences and behaviour. Furthermore, the culture and the practice of the units themselves influenced beliefs and attitudes of practitioners in compression force application. The strongest recommendation to emerge from this study was the need for peer observation to enable practitioners to observe and compare their own compression force practice to that of their colleagues. The findings are significant for clinical practice in order to understand how and why compression force is applied

Screening specifications for Gulf Coast salt domes

International Nuclear Information System (INIS)

Brunton, G.D.; Laughon, R.B.; McClain, W.C.

1978-01-01

A reconnaissance survey of the salt domes of Mississippi, Louisiana, and east Texas is being planned to identify study areas for potential sites for radioactive waste disposal. Preliminary screening specifications were derived for each of the geological evaluation criteria by application of the significant factors that will have an impact on the reconnaissance survey. The procedure for the derivation of each screening specification is discussed. The screening specifications are the official OWI values to be used for the first-cut acceptance for salt dome study areas along the Gulf Coast. The derivation of the screening specifications is illustrated by (1) a statement of the geological evaluation criterion, (2) a discussion of the pertinent factors affecting the criterion, and (3) the evaluation of the value of the specification

Premarital HIV screening in Johor--(2002-2004).

Science.gov (United States)

Khebir, B V; Adam, M A; Daud, A R; Shahrom, C M D

2007-03-01

A descriptive study was conducted on premarital HIV screening programme in Johor over a three year period. HIV screenings were done at government clinics and confirmed by accredited laboratories. As a result, 123 new HIV cases were detected (0.17%) from 74,210 respondents. In 2004, 24 cases (64.9%) advanced to marriage (n = 37) after they underwent counselling and six of them married among themselves. Positivity rate from this programme (0.17%) is higher than antenatal screening (0.05%). Despite the implementation of the premarital HIV screening programme, marriage application in Johor rose 2.8% in 2004 compared with 2002. This programme had partly contributed to public awareness against HIV and provides another option in early detection of the disease.

Application of polyaniline dispersions by means of screen printing

Czech Academy of Sciences Publication Activity Database

Držková, M.; Peřinka, N.; Hajná, Milena; Kaplanová, M.; Stejskal, Jaroslav

2013-01-01

Roč. 19, č. 2013 (2013), s. 257-268 ISSN 1211-5541 R&D Projects: GA TA ČR TE01020022 Institutional support: RVO:61389013 Keywords : polyaniline * colloids * screen printing Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

Building a virtual ligand screening pipeline using free software: a survey.

Science.gov (United States)

Glaab, Enrico

2016-03-01

Virtual screening, the search for bioactive compounds via computational methods, provides a wide range of opportunities to speed up drug development and reduce the associated risks and costs. While virtual screening is already a standard practice in pharmaceutical companies, its applications in preclinical academic research still remain under-exploited, in spite of an increasing availability of dedicated free databases and software tools. In this survey, an overview of recent developments in this field is presented, focusing on free software and data repositories for screening as alternatives to their commercial counterparts, and outlining how available resources can be interlinked into a comprehensive virtual screening pipeline using typical academic computing facilities. Finally, to facilitate the set-up of corresponding pipelines, a downloadable software system is provided, using platform virtualization to integrate pre-installed screening tools and scripts for reproducible application across different operating systems. © The Author 2015. Published by Oxford University Press.

Virtual screening methods as tools for drug lead discovery from large chemical libraries.

Science.gov (United States)

Ma, X H; Zhu, F; Liu, X; Shi, Z; Zhang, J X; Yang, S Y; Wei, Y Q; Chen, Y Z

2012-01-01

Virtual screening methods have been developed and explored as useful tools for searching drug lead compounds from chemical libraries, including large libraries that have become publically available. In this review, we discussed the new developments in exploring virtual screening methods for enhanced performance in searching large chemical libraries, their applications in screening libraries of ~ 1 million or more compounds in the last five years, the difficulties in their applications, and the strategies for further improving these methods.

Non-visit-based cancer screening using a novel population management system.

Science.gov (United States)

Atlas, Steven J; Zai, Adrian H; Ashburner, Jeffrey M; Chang, Yuchiao; Percac-Lima, Sanja; Levy, Douglas E; Chueh, Henry C; Grant, Richard W

2014-01-01

Advances in information technology (IT) now permit population-based preventive screening, but the best methods remain uncertain. We evaluated whether involving primary care providers (PCPs) in a visit-independent population management IT application led to more effective cancer screening. We conducted a cluster-randomized trial involving 18 primary care practice sites and 169 PCPs from June 15, 2011, to June 14, 2012. Participants included adults eligible for breast, cervical, and/or colorectal cancer screening. In practices randomized to the intervention group, PCPs reviewed real-time rosters of their patients overdue for screening and provided individualized contact (via a letter, practice delegate, or patient navigator) or deferred screening (temporarily or permanently). In practices randomized to the comparison group, overdue patients were automatically sent reminder letters and transferred to practice delegate lists for follow-up. Intervention patients without PCP action within 8 weeks defaulted to the automated control version. The primary outcome was adjusted average cancer screening completion rates over 1-year follow-up, accounting for clustering by physician or practice. Baseline cancer screening rates (80.8% vs 80.3%) were similar among patients in the intervention (n = 51,071) and comparison group (n = 52,799). Most intervention providers used the IT application (88 of 101, 87%) and users reviewed 7984 patients overdue for at least 1 cancer screening (73% sent reminder letter, 6% referred directly to a practice delegate or patient navigator, and 21% deferred screening). In addition, 6128 letters were automatically sent to patients in the intervention group (total of 12,002 letters vs 16,378 letters in comparison practices; P management IT application resulted in similar cancer screening rates compared with an automated reminder system, but fewer patients were sent reminder letters. This suggests that PCPs were able to identify and exclude from contact

Electromagnetic radiation screening of semiconductor devices for long life applications

Science.gov (United States)

Hall, T. C.; Brammer, W. G.

1972-01-01

A review is presented of the mechanism of interaction of electromagnetic radiation in various spectral ranges, with various semiconductor device defects. Previous work conducted in this area was analyzed as to its pertinence to the current problem. The task was studied of implementing electromagnetic screening methods in the wavelength region determined to be most effective. Both scanning and flooding type stimulation techniques are discussed. While the scanning technique offers a considerably higher yield of useful information, a preliminary investigation utilizing the flooding approach is first recommended because of the ease of implementation, lower cost and ability to provide go-no-go information in semiconductor screening.

Molecular theory of partial molar volume and its applications to biomolecular systems

Directory of Open Access Journals (Sweden)

T.Imai

2007-09-01

Full Text Available The paial molar volume (PMV is a thermodynamic quantity which contains important information about the solute-solvent interactions as well as the solute structure in solution.Additionally, the PMV is the most essential quantity in the analysis of the pressure effect on chemical reactions. This aicle reviews the recent developments in molecular theories of the PMV, especially the reference interaction site model (RISMtheory of molecular liquids and its three-dimensional generalization version (3D-RISM, which are combined with the Kirkwood-Buff solution theory to calculate the PMV. This aicle also introduces our recent applications of the theory to some interesting issues concerning the PMV of biomolecules. In addition, theoretical representations of the effects of intramolecular fluctuation on the PMV, which are significant for biomacromolecules, are briefly discussed.

Electron screening in molecular fusion reactions

International Nuclear Information System (INIS)

Shoppa, T.D.

1996-01-01

Recent laboratory experiments have measured fusion cross sections at center-of-mass energies low enough for the effects of atomic and molecular electrons to be important. To extract the cross section for bare nuclei from these data (as required for astrophysical applications), it is necessary to understand these screening effects. We study electron screening effects in the low-energy collisions of Z=1 nuclei with hydrogen molecules. Our model is based on a dynamical evolution of the electron wave functions within the TDHF scheme, while the motion of the nuclei is treated classically. We find that at the currently accessible energies the screening effects depend strongly on the molecular orientation. The screening is found to be larger for molecular targets than for atomic targets, due to the reflection symmetry in the latter. The results agree fairly well with data measured for deuteron collisions on molecular deuterium and tritium targets. (orig.)

Batch fabrication of disposable screen printed SERS arrays.

Science.gov (United States)

Qu, Lu-Lu; Li, Da-Wei; Xue, Jin-Qun; Zhai, Wen-Lei; Fossey, John S; Long, Yi-Tao

2012-03-07

A novel facile method of fabricating disposable and highly reproducible surface-enhanced Raman spectroscopy (SERS) arrays using screen printing was explored. The screen printing ink containing silver nanoparticles was prepared and printed on supporting materials by a screen printing process to fabricate SERS arrays (6 × 10 printed spots) in large batches. The fabrication conditions, SERS performance and application of these arrays were systematically investigated, and a detection limit of 1.6 × 10(-13) M for rhodamine 6G could be achieved. Moreover, the screen printed SERS arrays exhibited high reproducibility and stability, the spot-to-spot SERS signals showed that the intensity variation was less than 10% and SERS performance could be maintained over 12 weeks. Portable high-throughput analysis of biological samples was accomplished using these disposable screen printed SERS arrays.

Suomi NPP VIIRS solar diffuser screen transmittance model and its applications.

Science.gov (United States)

Lei, Ning; Xiong, Xiaoxiong; Mcintire, Jeff

2017-11-01

The visible infrared imaging radiometer suite on the Suomi National Polar-orbiting Partnership satellite calibrates its reflective solar bands through observations of a sunlit solar diffuser (SD) panel. Sunlight passes through a perforated plate, referred to as the SD screen, before reaching the SD. It is critical to know whether the SD screen transmittance measured prelaunch is accurate. Several factors such as misalignments of the SD panel and the measurement apparatus could lead to errors in the measured transmittance and thus adversely impact on-orbit calibration quality through the SD. We develop a mathematical model to describe the transmittance as a function of the angles that incident light makes with the SD screen, and apply the model to fit the prelaunch measured transmittance. The results reveal that the model does not reproduce the measured transmittance unless the size of the apertures in the SD screen is quite different from the design value. We attribute the difference to the orientation alignment errors for the SD panel and the measurement apparatus. We model the alignment errors and apply our transmittance model to fit the prelaunch transmittance to retrieve the "true" transmittance. To use this model correctly, we also examine the finite source size effect on the transmittance. Furthermore, we compare the product of the retrieved "true" transmittance and the prelaunch SD bidirectional reflectance distribution function (BRDF) value to the value derived from on-orbit data to determine whether the prelaunch SD BRDF value is relatively accurate. The model is significant in that it can evaluate whether the SD screen transmittance measured prelaunch is accurate and help retrieve the true transmittance from the transmittance with measurement errors, consequently resulting in a more accurate sensor data product by the same amount.

Studies Comparing Screen-Film Mammography and Full-Field Digital Mammography in Breast Cancer Screening: Updated Review

International Nuclear Information System (INIS)

Skaane, P.

2009-01-01

Full-field digital mammography (FFDM) has several potential benefits as compared with screen-film mammography (SFM) in mammography screening. Digital technology also opens for implementation of advanced applications, including computer-aided detection (CAD) and tomosynthesis. Phantom studies and experimental clinical studies have shown that FFDM is equal or slightly superior to SFM for detection and characterization of mammographic abnormalities. Despite obvious advantages, the conversion to digital mammography has been slower than anticipated, and not only due to higher costs. Until very recently, some countries did not even permit the use of digital mammography in breast cancer screening. The reason for this reluctant attitude was concern about lower spatial resolution and about using soft-copy reading. Furthermore, there was a lack of data supporting improved diagnostic accuracy using FFDM in a screening setting, since two pioneer trials both showed nonsignificantly lower cancer detection rate at FFDM. The 10 studies comparing FFDM and SFM in mammography screening published so far have shown divergent and rather conflicting results. Nevertheless, there is a rapid conversion to digital mammography in breast cancer screening in many western countries. The aim of this article is to give an updated review of these studies, discuss the conflicting findings, and draw some conclusions from the results

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

Science.gov (United States)

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

2010-01-01

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

Screening Applications to Test Cellular Fitness in Transwell® Models After Nanoparticle Treatment.

Science.gov (United States)

Christ, Bastian; Fey, Christina; Cubukova, Alevtina; Walles, Heike; Dembski, Sofia; Metzger, Marco

2017-01-01

Nanoparticles (NPs) in biotechnology hold great promise for revolutionizing medical treatments and therapies. In order to bring NPs into clinical application there is a number of preclinical in vitro and in vivo tests, which have to be applied before. The initial in vitro evaluation includes a detailed physicochemical characterization as well as biocompatibility tests, among others. For determination of biocompatibility at the cellular level, the correct choice of the in vitro assay as well as NP pretreatment is absolutely essential. There are a variety of assay technologies available that use standard plate readers to measure metabolic markers to estimate the number of viable cells in culture. Each cell viability assay has its own set of advantages and disadvantages. Regardless of the assay method chosen, the major factors critical for reproducibility and success include: (1) choosing the right assay after comparing optical NP properties with the read-out method of the assay, (2) verifying colloidal stability of NPs in cell culture media, (3) preparing a sterile and stable NP dispersion in cell culture media used in the assay, (4) using a tightly controlled and consistent cell model allowing appropriate characterization of NPs. This chapter will briefly summarize these different critical points, which can occur during biocompatibility screening applications of NPs.

Label-free screening of single biomolecules through resistive pulse sensing technology for precision medicine applications

Science.gov (United States)

Harrer, S.; Kim, S. C.; Schieber, C.; Kannam, S.; Gunn, N.; Moore, S.; Scott, D.; Bathgate, R.; Skafidas, S.; Wagner, J. M.

2015-05-01

systems genomics has to be accompanied by an equally strong effort to develop next-generation DNA-sequencing and next-generation drug screening and design platforms. In that context lab-on-a-chip devices utilizing nanopore- and nanochannel based resistive pulse-sensing technology for DNA-sequencing and protein screening applications occupy a key role. This paper describes the status quo of resistive pulse sensing technology for these two application areas with a special focus on current technology trends and challenges ahead.

Label-free screening of single biomolecules through resistive pulse sensing technology for precision medicine applications.

Science.gov (United States)

Harrer, S; Kim, S C; Schieber, C; Kannam, S; Gunn, N; Moore, S; Scott, D; Bathgate, R; Skafidas, S; Wagner, J M

2015-05-08

systems genomics has to be accompanied by an equally strong effort to develop next-generation DNA-sequencing and next-generation drug screening and design platforms. In that context lab-on-a-chip devices utilizing nanopore- and nanochannel based resistive pulse-sensing technology for DNA-sequencing and protein screening applications occupy a key role. This paper describes the status quo of resistive pulse sensing technology for these two application areas with a special focus on current technology trends and challenges ahead.

Initial screening of thermal desorption for soil remediation

International Nuclear Information System (INIS)

Yezzi, J.J. Jr.; Tafuri, A.N.; Rosenthal, S.; Troxler, W.L.

1994-01-01

Petroleum-contaminated soils--caused by spills, leaks, and accidental discharges--exist at many sites throughout the United States. Thermal desorption technologies which are increasingly being employed to treat these soils, have met soil cleanup criteria for a variety of petroleum products. Currently the United States Environmental Protection Agency is finalizing a technical report entitled Use of Thermal Desorption for Treating Petroleum-Contaminated Soils to assist remedial project managers, site owners, remediation contractors, and equipment vendors in evaluating the use of thermal desorption technologies for petroleum-contaminated soil applications. The report will present a three-level screening method to help a reader predict the success of applying thermal desorption at a specific site. The objective of screening level one is to determine the likelihood of success in a specific application of thermal desorption. It will take into account procedures for collecting and evaluating data on site characteristics, contaminant characteristics, soil characteristics, and regulatory requirements. This level will establish whether or not thermal desorption should be evaluated further for site remediation, whether treatment should occur on-site or off-site, and if on-site is a viable option, what system size will be most cost-effective. The scope of this paper addresses only screening level one which provides a preliminary assessment of the applicability of thermal desorption to a particular site. This topic encompasses worksheets that are an integral part of the ''user friendly'' screening process. Level one screening provides a foundation for the subsequent two levels which follow a similar ''user friendly'' worksheet approach to evaluating thermal desorption technologies and establishing costs for thermal desorption in an overall remediation project

A Study of Applications of Machine Learning Based Classification Methods for Virtual Screening of Lead Molecules.

Science.gov (United States)

Vyas, Renu; Bapat, Sanket; Jain, Esha; Tambe, Sanjeev S; Karthikeyan, Muthukumarasamy; Kulkarni, Bhaskar D

2015-01-01

The ligand-based virtual screening of combinatorial libraries employs a number of statistical modeling and machine learning methods. A comprehensive analysis of the application of these methods for the diversity oriented virtual screening of biological targets/drug classes is presented here. A number of classification models have been built using three types of inputs namely structure based descriptors, molecular fingerprints and therapeutic category for performing virtual screening. The activity and affinity descriptors of a set of inhibitors of four target classes DHFR, COX, LOX and NMDA have been utilized to train a total of six classifiers viz. Artificial Neural Network (ANN), k nearest neighbor (k-NN), Support Vector Machine (SVM), Naïve Bayes (NB), Decision Tree--(DT) and Random Forest--(RF). Among these classifiers, the ANN was found as the best classifier with an AUC of 0.9 irrespective of the target. New molecular fingerprints based on pharmacophore, toxicophore and chemophore (PTC), were used to build the ANN models for each dataset. A good accuracy of 87.27% was obtained using 296 chemophoric binary fingerprints for the COX-LOX inhibitors compared to pharmacophoric (67.82%) and toxicophoric (70.64%). The methodology was validated on the classical Ames mutagenecity dataset of 4337 molecules. To evaluate it further, selectivity and promiscuity of molecules from five drug classes viz. anti-anginal, anti-convulsant, anti-depressant, anti-arrhythmic and anti-diabetic were studied. The TPC fingerprints computed for each category were able to capture the drug-class specific features using the k-NN classifier. These models can be useful for selecting optimal molecules for drug design.

LC-MS (/MS) in clinical toxicology screening methods.

Science.gov (United States)

Viette, Véronique; Hochstrasser, Denis; Fathi, Marc

2012-01-01

Toxicological screening is the analysis of biological samples to detect and identify unknown compounds. The high selectivity and sensitivity of liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) technology provide an attractive alternative to the current methods (LC-UV, GC/MS, etc.). For these reasons, an increasing number of applications are being published. This paper is a brief overview of LC-MS(/MS) screening methods developed for clinical toxicology in recent years. Various sample treatments, chromatographic separations and detection by mass spectrometry can be combined to obtain screening methods adapted to the constraints and needs of clinical toxicology laboratories. Currently the techniques are in the hands of specialists, mainly in academic institutions. However, the evolution in technology should allow application of these techniques as a tool in toxicology laboratories, thus allowing a more widespread exploitation of their potential.

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

Science.gov (United States)

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

2005-03-01

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

Screening strategies for tuberculosis prevalence surveys: the value of chest radiography and symptoms.

Directory of Open Access Journals (Sweden)

Anna H van't Hoog

Full Text Available We conducted a tuberculosis (TB prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding.All participants with a positive screen on either a symptom questionnaire, chest radiography (CXR and/or sputum smear microscopy submitted sputum for culture. HIV status was obtained from prevalent cases. We estimated the accuracy of modified screening strategies with bacteriologically confirmed TB as the gold standard, and compared these with other survey reports. We also assessed whether sequential rather than parallel application of symptom, CXR and HIV screening would substantially reduce the number of participants requiring CXR and/or sputum culture.Presence of any abnormality on CXR had 94% (95%CI 88-98 sensitivity (92% in HIV-infected and 100% in HIV-uninfected and 73% (95%CI 68-77 specificity. Symptom screening combinations had significantly lower sensitivity than CXR except for 'any TB symptom' which had 90% (95%CI 84-95 sensitivity (96% in HIV-infected and 82% in HIV-uninfected and 32% (95%CI 30-34 specificity. Smear microscopy did not yield additional suspects, thus the combined symptom/CXR screen applied in the survey had 100% (95%CI 97-100 sensitivity. Specificity was 65% (95%CI 61-68. Sequential application of first a symptom screen for 'any symptom', followed by CXR-evaluation and different suspect criteria depending on HIV status would result in the largest reduction of the need for CXR and sputum culture, approximately 36%, but would underestimate prevalence by 11%.CXR screening alone had higher accuracy compared to symptom screening alone. Combined CXR and symptom screening had the highest sensitivity and remains important for suspect identification in TB prevalence surveys in settings where bacteriological sputum examination of all participants is not

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.

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

Science.gov (United States)

Kim, Jennifer; Kyung, Richard

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

A Sign Language Screen Reader for Deaf

Science.gov (United States)

El Ghoul, Oussama; Jemni, Mohamed

Screen reader technology has appeared first to allow blind and people with reading difficulties to use computer and to access to the digital information. Until now, this technology is exploited mainly to help blind community. During our work with deaf people, we noticed that a screen reader can facilitate the manipulation of computers and the reading of textual information. In this paper, we propose a novel screen reader dedicated to deaf. The output of the reader is a visual translation of the text to sign language. The screen reader is composed by two essential modules: the first one is designed to capture the activities of users (mouse and keyboard events). For this purpose, we adopted Microsoft MSAA application programming interfaces. The second module, which is in classical screen readers a text to speech engine (TTS), is replaced by a novel text to sign (TTSign) engine. This module converts text into sign language animation based on avatar technology.

CLAD DEGRADATION - FEPS SCREENING ARGUMENTS

International Nuclear Information System (INIS)

R. Schreiner

2004-01-01

The purpose of this report is to evaluate and document the screening of the clad degradation features, events, and processes (FEPs) with respect to modeling used to support the Total System Performance Assessment-License Application (TSPA-LA). This report also addresses the effect of certain FEPs on both the cladding and the commercial spent nuclear fuel (CSNF), DOE-owned spent nuclear fuel (DSNF), and defense high-level waste (DHLW) waste forms, as appropriate to address the effects on multiple materials and both components (FEPs 2.1.09.09.0A, 2.1.09.11.0A, 2.1.11.05.0A, 2.1.12.02.0A, and 2.1.12.03.0A). These FEPs are expected to affect the repository performance during the postclosure regulatory period of 10,000 years after permanent closure. Table 1-1 provides the list of cladding FEPs, including their screening decisions (include or exclude). The primary purpose of this report is to identify and document the analysis, screening decision, and TSPA-LA disposition (for included FEPs) or screening argument (for excluded FEPs) for these FEPs related to clad degradation. In some cases, where a FEP covers multiple technical areas and is shared with other FEP reports, this report may provide only a partial technical basis for the screening of the FEP. The full technical basis for shared FEPs is addressed collectively by the sharing FEP reports. The screening decisions and associated TSPA-LA dispositions or screening arguments from all of the FEP reports are cataloged in a project-specific FEPs database

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

Science.gov (United States)

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

2017-12-01

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

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

Directory of Open Access Journals (Sweden)

Rebecca F Alford

2017-12-01

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

Four Principles to Consider Before Advising Women on Screening Mammography

DEFF Research Database (Denmark)

Keen, John D; Juhl Jørgensen, Karsten

2015-01-01

This article reviews four important screening principles applicable to screening mammography in order to facilitate informed choice. The first principle is that screening may help, hurt, or have no effect. In order to reduce mortality and mastectomy rates, screening must reduce the rate of advanced...... of a screening intervention. Disease-specific mortality is biased due to difficulties in attribution of cause of death and to increased mortality due to overdiagnosis and the resulting overtreatment with radiotherapy and chemotherapy. To enhance participation, the benefit from screening is often presented...... in relative instead of absolute terms. Third, some screening statistics must be interpreted with caution. Increased survival time and the percentage of early-stage tumors at detection sound plausible, but are affected by lead-time and length biases. In addition, analyses that only include women who attend...

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.

Author Details

African Journals Online (AJOL)

Goud, MJP. Vol 2, No 3 (2007) - Articles Antibacterial activity and biomolecular composition of certain fresh water micro-algae from River Godavari (India) Abstract PDF · Vol 3, No 1 (2008) - Articles Replica plate screening method for detecting phosphatase activity in basidiomycetes using 1-Napthyl Phosphate as a ...

Screening Strategies for Tuberculosis Prevalence Surveys: The Value of Chest Radiography and Symptoms

NARCIS (Netherlands)

van't Hoog, Anna H.; Meme, Helen K.; Laserson, Kayla F.; Agaya, Janet A.; Muchiri, Benson G.; Githui, Willie A.; Odeny, Lazarus O.; Marston, Barbara J.; Borgdorff, Martien W.

2012-01-01

Background: We conducted a tuberculosis (TB) prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding. Methods: All

Comparative analysis of pharmacophore screening tools.

NARCIS (Netherlands)

Sanders, M.P.A.; Barbosa, A.J.; Zarzycka, B.; Nicolaes, G.A.; Klomp, J.P.G.; Vlieg, J. de; Rio, A. Del

2012-01-01

The pharmacophore concept is of central importance in computer-aided drug design (CADD) mainly because of its successful application in medicinal chemistry and, in particular, high-throughput virtual screening (HTVS). The simplicity of the pharmacophore definition enables the complexity of molecular

Interfacing of DNA with carbon nanotubes for nanodevice applications

International Nuclear Information System (INIS)

Rastogi, Richa; Dhindsa, Navneet; Suri, C. Raman; Pant, B.D.; Tripathi, S.K.; Kaur, Inderpreet; Bharadwaj, Lalit M.

2012-01-01

In nanotechnology, carbon nanotubes are evolving as ‘hot spot’ due to their applications as most sensitive biosensors. Thus, study of effect of biomolecular interaction is prerequisite for their electrical application in biosensors and bioelectronics. Here, we have explored this effect on electrical properties of carbon nanotubes with DNA as a model biomolecule. A stable conjugate of carbon nanotubes with DNA is formed via covalent methodology employing quantum dot as fluoropore and characterized with various spectroscopic, fluoroscopic and microscopic techniques. CNT–DNA adduct showed decreased transconductance (from 614.46 μS to 1.34 μS) and shift of threshold voltage (from −0.85 V to 2.5 V) due to change in Schottky barriers at metal–nanotube contact. In addition, decrease in hole mobility (from 4.46 × 10 6 to 9.72 × 10 3 cm 2 V −1 s −1 ) and increase in ON-linear resistance (from 74 kΩ to 0.44 MΩ) conclude large change in device parameters. On the one hand, this substantial change in device parameters after interfacing with biomolecules supports application of carbon nanotubes in the field of biosensors while on the other hand, the same can limit their use in future power electronic devices where stability in device parameters is essential. -- Graphical abstract: Carbon nanotubes are interfaced with DNA via covalent interactions and characterized with spectroscopic, fluoroscopic and microscopic techniques. Electrical characterization of this stable SWNT–DNA conjugate shows decreased transconductance and shift of threshold voltage towards positive gate voltages. On the one hand, this substantial change in device parameters after interfacing with biomolecules supports application of carbon nanotubes in the field of biosensors while on the other hand, the same can limit their use in future power electronic devices where stability in device parameters is essential. Highlights: ► Effect of biomolecular (DNA) interaction on electrical

The urgent need for universally applicable simple screening procedures and diagnostic criteria for gestational diabetes mellitus - lessons from projects funded by the World Diabetes Foundation

DEFF Research Database (Denmark)

Nielsen, Karoline Kragelund; de Courten, Maximilian; Kapur, Anil

2012-01-01

, in implementing the guidelines. These projects have reached out to thousands of pregnant women through capacity building and improvement of access to GDM screening and diagnosis in the developing world and therefore provide a rich field experience on the applicability of the guidelines in resource-poor settings......: This study aimed to investigate whether GDM projects supported by the World Diabetes Foundation in developing countries utilize any of the internationally recommended guidelines for screening and diagnosis of GDM, explore experiences on applicability and usefulness of the guidelines and barriers if any....... Design: A mixed methods approach using questionnaires and interviews was utilised to review 11 GDM projects. Two projects were conducted by the same partner; interviews were conducted in person or via phone by the first author with nine project partners and one responded via email. The interviews were...

ScreenCube: A 3D Printed System for Rapid and Cost-Effective Chemical Screening in Adult Zebrafish.

Science.gov (United States)

Monstad-Rios, Adrian T; Watson, Claire J; Kwon, Ronald Y

2018-02-01

Phenotype-based small molecule screens in zebrafish embryos and larvae have been successful in accelerating pathway and therapeutic discovery for diverse biological processes. Yet, the application of chemical screens to adult physiologies has been relatively limited due to additional demands on cost, space, and labor associated with screens in adult animals. In this study, we present a 3D printed system and methods for intermittent drug dosing that enable rapid and cost-effective chemical administration in adult zebrafish. Using prefilled screening plates, the system enables dosing of 96 fish in ∼3 min, with a 10-fold reduction in drug quantity compared to that used in previous chemical screens in adult zebrafish. We characterize water quality kinetics during immersion in the system and use these kinetics to rationally design intermittent dosing regimens that result in 100% fish survival. As a demonstration of system fidelity, we show the potential to identify two known chemical inhibitors of adult tail fin regeneration, cyclopamine and dorsomorphin. By developing methods for rapid and cost-effective chemical administration in adult zebrafish, this study expands the potential for small molecule discovery in postembryonic models of development, disease, and regeneration.

Screens

OpenAIRE

2016-01-01

This Sixth volume in the series The Key Debates. Mutations and Appropriations in European Film Studies investigates the question of screens in the context both of the dematerialization due to digitalization and the multiplication of media screens. Scholars offer various infomations and theories of topics such as the archeology of screen, film and media theories, contemporary art, pragmatics of new ways of screening (from home video to street screening).

Development and Application of High-Content Biological Screening for Modulators of NET Production

Directory of Open Access Journals (Sweden)

Ilaria J. Chicca

2018-03-01

Full Text Available Neutrophil extracellular traps (NETs are DNA-based antimicrobial web-like structures whose release is predominantly mediated by reactive oxygen species (ROS; their purpose is to combat infections. However, unbalanced NET production and clearance is involved in tissue injury, circulation of auto-antibodies and development of several chronic diseases. Currently, there is lack of agreement regarding the high-throughput methods available for NET investigation. This study, therefore, aimed to develop and optimize a high-content analysis (HCA approach, which can be applied for the assay of NET production and for the screening of compounds involved in the modulation of NET release. A suitable paraformaldehyde fixation protocol was established to enable HCA of neutrophils and NETs. Bespoke and in-built bioinformatics algorithms were validated by comparison with standard low-throughput approaches for application in HCA of NETs. Subsequently, the optimized protocol was applied to high-content screening (HCS of a pharmaceutically derived compound library to identify modulators of NETosis. Of 56 compounds assessed, 8 were identified from HCS for further characterization of their effects on NET formation as being either inducers, inhibitors or biphasic modulators. The effects of these compounds on naïve neutrophils were evaluated by using specific assays for the induction of ROS and NET production, while their modulatory activity was validated in phorbol 12-myristate 13-acetate-stimulated neutrophils. Results indicated the involvement of glutathione reductase, Src family kinases, molecular-target-of-Rapamycin, and mitogen-activated-protein-kinase pathways in NET release. The compounds and pathways identified may provide targets for novel therapeutic approaches for treating NET-associated pathologies.

Data Analysis and Neuro-Fuzzy Technique for EOR Screening: Application in Angolan Oilfields

Directory of Open Access Journals (Sweden)

Geraldo A. R. Ramos

2017-06-01

Full Text Available In this work, a neuro-fuzzy (NF simulation study was conducted in order to screen candidate reservoirs for enhanced oil recovery (EOR projects in Angolan oilfields. First, a knowledge pattern is extracted by combining both the searching potential of fuzzy-logic (FL and the learning capability of neural network (NN to make a priori decisions. The extracted knowledge pattern is validated against rock and fluid data trained from successful EOR projects around the world. Then, data from Block K offshore Angolan oilfields are then mined and analysed using box-plot technique for the investigation of the degree of suitability for EOR projects. The trained and validated model is then tested on the Angolan field data (Block K where EOR application is yet to be fully established. The results from the NF simulation technique applied in this investigation show that polymer, hydrocarbon gas, and combustion are the suitable EOR techniques.

Screening EEG in Aircrew Selection: Clinical Aerospace Neurology Perspective

Science.gov (United States)

Clark, Jonathan B.; Riley, Terrence

2001-01-01

As clinical aerospace neurologists we do not favor using screening EEG in pilot selection on unselected and otherwise asymptomatic individuals. The role of EEG in aviation screening should be as an adjunct to diagnosis, and the decision to disqualify a pilot should never be based solely on the EEG. Although a policy of using a screening EEG in an unselected population might detect an individual with a potentially increased relative risk, it would needlessly exclude many applicants who would probably never have a seizure. A diagnostic test performed on an asymptomatic individual without clinical indications, in a population with a low prevalence of disease (seizure) may be of limited or possibly detrimental value. We feel that rather than do EEGs on all candidates, a better approach would be to perform an EEG for a specific indication, such as family history of seizure, single convulsion (seizure) , history of unexplained loss of consciousness or head injury. Routine screening EEGs in unselected aviation applications are not done without clinical indication in the U.S. Air Force, Navy, or NASA. The USAF discontinued routine screening EEGs for selection in 1978, the U.S. Navy discontinued it in 1981 , and NASA discontinued it in 1995. EEG as an aeromedical screening tool in the US Navy dates back to 1939. The US Navy routinely used EEGs to screen all aeromedical personnel from 1961 to 1981. The incidence of epileptiform activity on EEG in asymptomatic flight candidates ranges from 0.11 to 2.5%. In 3 studies of asymptomatic flight candidates with epileptiform activity on EEG followed for 2 to 15 years, 1 of 31 (3.2%), 1 of 30 (3.3%), and 0 of 14 (0%) developed a seizure, for a cumulative risk of an individual with an epileptiform EEG developing a seizure of 2.67% (2 in 75). Of 28,658 student naval aviation personnel screened 31 had spikes and/or slow waves on EEG, and only 1 later developed a seizure. Of the 28,627 who had a normal EEG, 4 later developed seizures, or

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

Science.gov (United States)

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

2016-06-08

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

Application of the Perceptual Factors, Enabling and Reinforcing Model on Pap Smaear Screening in Iranian Northern Woman

Directory of Open Access Journals (Sweden)

Abolhassan Naghibi

2016-03-01

Full Text Available Background and Purpose: Cervical cancer is the most prevalent cancer among women in the world. Cervical cancer is no symptoms and can be treated if diagnosed in the first stage of the disease. The aim of this study was to survey the affecting factors of the Pap smears test on perceptual factors, enabling and reinforcing (PEN-3 model constructs in women. Materials and Methods: This study was a descriptive cross-sectional study. The sample size was 416 married women with random sampling. The questionnaire had 50 questions based on PEN-3 model structures. Data were analyzed by descriptive statistics and logistic regression method in software SPSS 20. Results: The mean age of women was 32.70 ± 21.00 years. The knowledge of risk factors and screening methods for cervical cancer was 37.2. About 40% of women had a history of Pap smears. The most important of perception factors were effective, family history of the disease, encourage people to Pap smear, and fear of detecting of cervical cancer. The most important enabling factors were the presence of expert health personnel to provide training and Pap smear test (50.3%, lack of time and too busy to do Pap smear test (23.2%. The reinforcing factors were the media advice (41.3%, doctor’s advice (32.5% and neglect and forgetfulness (36.2%. Conclusion: This study has shown the Pap smear screening behavior affected by personal factors, family, cultural and economic. Application of PEN-3 can effective in planning and designing intervention programs for cervical cancer screening.

A globally applicable location-specific screening model for assessing the relative risk of pesticide leaching

International Nuclear Information System (INIS)

Whelan, M.J.; Davenport, E.J.; Smith, B.G.

2007-01-01

A screening model of pesticide leaching loss is described which forms part of a multi-criteria risk-based indicator system called PRoMPT (Pesticide Risk Management and Profiling Tool). The leaching model evaluates pesticide fate in soil for any application rate and time of application (including multiple applications), for any land-based location in the world. It considers a generic evaluative environment with fixed dimensions and soil properties. The soil profile is conceptualised as a number of discrete layers. Equilibrium partitioning between adsorbed and dissolved chemical (based on the organic carbon-water partition coefficient [K OC ]) is assumed in each time step, in each layer. Non-leaching losses are described using first order kinetics. Drainage is assumed to be uniform throughout the soil profile but varies temporally. The drainage rate, which can be augmented by evapotranspiration-adjusted irrigation, is derived from long-term mean monthly water balance model calculations performed for 30 arc-minute grid cells across the entire ice-free land surface of the earth. Although, such predictions are approximate, they do capture the seasonality and relative magnitude of drainage and allow the model to be applied anywhere, without the need for extensive data compilation. PRoMPT predictions are shown to be consistent with those made by more sophisticated models (PRZM, PELMO and PEARL) for the FOCUS groundwater scenarios

A globally applicable location-specific screening model for assessing the relative risk of pesticide leaching

Energy Technology Data Exchange (ETDEWEB)

Whelan, M.J. [Unilever Safety and Environmental Assurance Centre, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ (United Kingdom)]. E-mail: mick.whelan@unilever.com; Davenport, E.J. [Unilever Safety and Environmental Assurance Centre, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ (United Kingdom); Smith, B.G. [Unilever Sustainable Agriculture Team, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ (United Kingdom)

2007-05-15

A screening model of pesticide leaching loss is described which forms part of a multi-criteria risk-based indicator system called PRoMPT (Pesticide Risk Management and Profiling Tool). The leaching model evaluates pesticide fate in soil for any application rate and time of application (including multiple applications), for any land-based location in the world. It considers a generic evaluative environment with fixed dimensions and soil properties. The soil profile is conceptualised as a number of discrete layers. Equilibrium partitioning between adsorbed and dissolved chemical (based on the organic carbon-water partition coefficient [K {sub OC}]) is assumed in each time step, in each layer. Non-leaching losses are described using first order kinetics. Drainage is assumed to be uniform throughout the soil profile but varies temporally. The drainage rate, which can be augmented by evapotranspiration-adjusted irrigation, is derived from long-term mean monthly water balance model calculations performed for 30 arc-minute grid cells across the entire ice-free land surface of the earth. Although, such predictions are approximate, they do capture the seasonality and relative magnitude of drainage and allow the model to be applied anywhere, without the need for extensive data compilation. PRoMPT predictions are shown to be consistent with those made by more sophisticated models (PRZM, PELMO and PEARL) for the FOCUS groundwater scenarios.

Nutrition screening tools: an analysis of the evidence.

Science.gov (United States)

Skipper, Annalynn; Ferguson, Maree; Thompson, Kyle; Castellanos, Victoria H; Porcari, Judy

2012-05-01

In response to questions about tools for nutrition screening, an evidence analysis project was developed to identify the most valid and reliable nutrition screening tools for use in acute care and hospital-based ambulatory care settings. An oversight group defined nutrition screening and literature search criteria. A trained analyst conducted structured searches of the literature for studies of nutrition screening tools according to predetermined criteria. Eleven nutrition screening tools designed to detect undernutrition in patients in acute care and hospital-based ambulatory care were identified. Trained analysts evaluated articles for quality using criteria specified by the American Dietetic Association's Evidence Analysis Library. Members of the oversight group assigned quality grades to the tools based on the quality of the supporting evidence, including reliability and validity data. One tool, the NRS-2002, received a grade I, and 4 tools-the Simple Two-Part Tool, the Mini-Nutritional Assessment-Short Form (MNA-SF), the Malnutrition Screening Tool (MST), and Malnutrition Universal Screening Tool (MUST)-received a grade II. The MST was the only tool shown to be both valid and reliable for identifying undernutrition in the settings studied. Thus, validated nutrition screening tools that are simple and easy to use are available for application in acute care and hospital-based ambulatory care settings.

Screensaver: an open source lab information management system (LIMS for high throughput screening facilities

Directory of Open Access Journals (Sweden)

Nale Jennifer

2010-05-01

Full Text Available Abstract Background Shared-usage high throughput screening (HTS facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups. Results We have developed Screensaver, a free, open source, web-based lab information management system (LIMS, to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects. Conclusions The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities.

Screensaver: an open source lab information management system (LIMS) for high throughput screening facilities.

Science.gov (United States)

Tolopko, Andrew N; Sullivan, John P; Erickson, Sean D; Wrobel, David; Chiang, Su L; Rudnicki, Katrina; Rudnicki, Stewart; Nale, Jennifer; Selfors, Laura M; Greenhouse, Dara; Muhlich, Jeremy L; Shamu, Caroline E

2010-05-18

Shared-usage high throughput screening (HTS) facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups. We have developed Screensaver, a free, open source, web-based lab information management system (LIMS), to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects. The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities.

Detection of Antibiotics and Evaluation of Antibacterial Activity with Screen-Printed Electrodes

Directory of Open Access Journals (Sweden)

Florentina-Daniela Munteanu

2018-03-01

Full Text Available This review provides a brief overview of the fabrication and properties of screen-printed electrodes and details the different opportunities to apply them for the detection of antibiotics, detection of bacteria and antibiotic susceptibility. Among the alternative approaches to costly chromatographic or ELISA methods for antibiotics detection and to lengthy culture methods for bacteria detection, electrochemical biosensors based on screen-printed electrodes present some distinctive advantages. Chemical and (biosensors for the detection of antibiotics and assays coupling detection with screen-printed electrodes with immunomagnetic separation are described. With regards to detection of bacteria, the emphasis is placed on applications targeting viable bacterial cells. While the electrochemical sensors and biosensors face many challenges before replacing standard analysis methods, the potential of screen-printed electrodes is increasingly exploited and more applications are anticipated to advance towards commercial analytical tools.

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

Science.gov (United States)

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

2017-11-15

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

Clad Degradation - FEPs Screening Arguments

International Nuclear Information System (INIS)

E. Siegmann

2004-01-01

The purpose of this report is to document the screening of the cladding degradation features, events, and processes (FEPs) for commercial spent nuclear fuel (CSNF). This report also addresses the effect of some FEPs on both the cladding and the CSNF, DSNF, and HLW waste forms where it was considered appropriate to address the effects on both materials together. This report summarizes the work of others to screen clad degradation FEPs in a manner consistent with, and used in, the Total System Performance Assessment-License Application (TSPA-LA). This document was prepared according to ''Technical Work Plan for Waste Form Degradation Modeling, Testing, and Analyses in Support of LA'' (BSC 2004a [DIRS 167796])

Organic-resistant screen-printed graphitic electrodes: Application to on-site monitoring of liquid fuels.

Science.gov (United States)

Almeida, Eduardo S; Silva, Luiz A J; Sousa, Raquel M F; Richter, Eduardo M; Foster, Christopher W; Banks, Craig E; Munoz, Rodrigo A A

2016-08-31

This work presents the potential application of organic-resistant screen-printed graphitic electrodes (SPGEs) for fuel analysis. The required analysis of the antioxidant 2,6-di-tert-butylphenol (2,6-DTBP) in biodiesel and jet fuel is demonstrated as a proof-of-concept. The screen-printing of graphite, Ag/AgCl and insulator inks on a polyester substrate (250 μm thickness) resulted in SPGEs highly compatible with liquid fuels. SPGEs were placed on a batch-injection analysis (BIA) cell, which was filled with a hydroethanolic solution containing 99% v/v ethanol and 0.1 mol L(-1) HClO4 (electrolyte). An electronic micropipette was connected to the cell to perform injections (100 μL) of sample or standard solutions. Over 200 injections can be injected continuously without replacing electrolyte and SPGE strip. Amperometric detection (+1.1 V vs. Ag/AgCl) of 2,6-DTBP provided fast (around 8 s) and precise (RSD = 0.7%, n = 12) determinations using an external calibration curve. The method was applied for the analysis of biodiesel and aviation jet fuel samples and comparable results with liquid and gas chromatographic analyses, typically required for biodiesel and jet fuel samples, were obtained. Hence, these SPGE strips are completely compatible with organic samples and their combination with the BIA cell shows great promise for routine and portable analysis of fuels and other organic liquid samples without requiring sophisticated sample treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Breast cancer screening in Korean woman with dense breast tissue

International Nuclear Information System (INIS)

Shin, Hee Jung; Ko, Eun Sook; Yi, Ann

2015-01-01

Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results

Breast cancer screening in Korean woman with dense breast tissue

Energy Technology Data Exchange (ETDEWEB)

Shin, Hee Jung [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Ko, Eun Sook [Dept. of Radiology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Yi, Ann [Dept. of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

2015-11-15

Asian women, including Korean, have a relatively higher incidence of dense breast tissue, compared with western women. Dense breast tissue has a lower sensitivity for the detection of breast cancer and a higher relative risk for breast cancer, compared with fatty breast tissue. Thus, there were limitations in the mammographic screening for women with dense breast tissue, and many studies for the supplemental screening methods. This review included appropriate screening methods for Korean women with dense breasts. We also reviewed the application and limitation of supplemental screening methods, including breast ultrasound, digital breast tomosynthesis, and breast magnetic resonance imaging; and furthermore investigated the guidelines, as well as the study results.

Active versus passive screening for entrance control

International Nuclear Information System (INIS)

McCormick, N.J.

1976-01-01

The benefits of different entrance control actions are quantitatively assessed by defining a relative improvement index for the screening activity. Three classes of entrance control measures are investigated: the use of a purely active screening measure (such as a portal monitor), the use of a purely passive screening measure (such as personality typing), and the combined use of active and passive measures. Active entrance control measures have been studied previously [McCormick and Erdmann, Nucl. Mat. Manag. 4, (1975)] where it was determined that the relative improvement index is approximately related to the nondetection probability factor r for the protective system by (1-r + r ln r). It is shown here that the relative improvement index for a purely passive screening system also can be approximately expressed in a convenient manner. Because the probability is very small that a sabotage or diversion action would be attempted, the result for passive screening, multiplied by r, may be combined with the factor (1-r + r ln r) to give the relative improvement index for a combined, active-and-passive entrance control system. Results from simple example calculations indicate that passive screening of nuclear plant personnel or applicants for such positions is orders-of-magnitude less effective than portal monitors or reasonable improvements in them. 5 tables

Depression Screening

Science.gov (United States)

... Depression Screening Substance Abuse Screening Alcohol Use Screening Depression Screening (PHQ-9) - Instructions The following questions are ... this tool, there is also text-only version . Depression Screening - Manual Instructions The following questions are a ...

Using surveillance data to simulate the impact of a hypothetical pre-entry tuberculosis screening programme in Japan.

Science.gov (United States)

Kawatsu, L; Uchimura, K; Izumi, K; Ohkado, A; Kato, S

2018-05-01

Despite a growing burden of foreign-born tuberculosis (TB) patients, Japan does not currently practise pre-entry tuberculosis (TB) screening among foreign-born entrants. To evaluate the impact of a hypothetical pre-entry TB screening programme among new foreign-born entrants into Japan. Using publicly available sources, we estimated 1) the number of prevalent TB cases, defined as bacteriologically or clinically confirmed cases among new foreign-born entrants into Japan in 2015, and 2) the yield from a hypothetical pre-entry TB screening programme under three scenarios: Scenario A, in which screening would be required of all applicants intending to stay for 3 months; Scenario B, screening among applicants for visas for settlement purposes; and Scenario C, screening among student and technical intern visa applicants. The numbers of prevalent TB cases under Scenarios A, B and C were respectively 492, 54 and 248 out of a total of 328 791, 21 554 and 182 879 applicants, respectively 276, 29 and 137 of whom would be detected via the pre-entry screening programme, giving an yield of respectively 83.9, 134.5 and 74.9 per 100 000 screened under each scenario. The yield was the highest under Scenario B; however, the impact was greatest under Scenario A, in that it detected the greatest number of patients and thus contributed the most in reducing the burden of foreign-born TB cases in Japan.

Shale oil specialty markets: Screening survey for United States applications

Energy Technology Data Exchange (ETDEWEB)

1987-12-01

EG and G requested J. E. Sinor Consultants Inc. to carry out an initial screening study on the possibilities for producing specialty chemicals from oil shale. Raw shale oil is not an acceptable feedstock to refineries and there are not enough user of heavy fuel oil in the western oil shale region to provide a dependable market. The only alternatives are to hydrotreat the oil, or else ship it long distances to a larger market area. Either of these alternatives results in a cost penalty of several dollars per barrel. Instead of attempting to enter the large-volume petroleum products market, it was hypothesized that a small shale oil facility might be able to produce specialty chemicals with a high enough average value to absorb the high costs of shipping small quantities to distant markets and still provide a higher netback to the plant site than sales to the conventional petroleum products market. This approach, rather than attempting to refine shale oil or to modify its characteristics to satisfy the specifications for petroleum feedstocks or products, focuses instead on those particular characteristics which distinguish shale oil from petroleum, and attempts to identify applications which would justify a premium value for those distinctive characteristics. Because byproducts or specialty chemicals production has been a prominent feature of oil shale industries which have flourished for periods of time in various countries, a brief review of those industries provides a starting point for this study. 9 figs., 32 tabs.

Preflight screening techniques for centrifuge-simulated suborbital spaceflight.

Science.gov (United States)

Pattarini, James M; Blue, Rebecca S; Castleberry, Tarah L; Vanderploeg, James M

2014-12-01

Historically, space has been the venue of the healthy individual. With the advent of commercial spaceflight, we face the novel prospect of routinely exposing spaceflight participants (SPFs) with multiple comorbidities to the space environment. Preflight screening procedures must be developed to identify those individuals at increased risk during flight. We examined the responses of volunteers to centrifuge accelerations mimicking commercial suborbital spaceflight profiles to evaluate how potential SFPs might tolerate such forces. We evaluated our screening process for medical approval of subjects for centrifuge participation for applicability to commercial spaceflight operations. All registered subjects completed a medical questionnaire, physical examination, and electrocardiogram. Subjects with identified concerns including cardiopulmonary disease, hypertension, and diabetes were required to provide documentation of their conditions. There were 335 subjects who registered for the study, 124 who completed all prescreening, and 86 subjects who participated in centrifuge trials. Due to prior medical history, five subjects were disqualified, most commonly for psychiatric reasons or uncontrolled medical conditions. Of the subjects approved, four individuals experienced abnormal physiological responses to centrifuge profiles, including one back strain and three with anxiety reactions. The screening methods used were judged to be sufficient to identify individuals physically capable of tolerating simulated suborbital flight. Improved methods will be needed to identify susceptibility to anxiety reactions. While severe or uncontrolled disease was excluded, many subjects successfully participated in centrifuge trials despite medical histories of disease that are disqualifying under historical spaceflight screening regimes. Such screening techniques are applicable for use in future commercial spaceflight operations.

COLA with scale-dependent growth: applications to screened modified gravity models

Energy Technology Data Exchange (ETDEWEB)

Winther, Hans A.; Koyama, Kazuya; Wright, Bill S. [Institute of Cosmology and Gravitation, University of Portsmouth, Dennis Sciama Building, Burnaby Road, Portsmouth, PO1 3FX (United Kingdom); Manera, Marc [Centre for Theoretical Cosmology, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Zhao, Gong-Bo, E-mail: hans.a.winther@gmail.com, E-mail: kazuya.koyama@port.ac.uk, E-mail: manera.work@gmail.com, E-mail: bill.wright@port.ac.uk, E-mail: gong-bo.Zhao@port.ac.uk [National Astronomy Observatories, Chinese Academy of Science, Beijing, 100012 (China)

2017-08-01

We present a general parallelized and easy-to-use code to perform numerical simulations of structure formation using the COLA (COmoving Lagrangian Acceleration) method for cosmological models that exhibit scale-dependent growth at the level of first and second order Lagrangian perturbation theory. For modified gravity theories we also include screening using a fast approximate method that covers all the main examples of screening mechanisms in the literature. We test the code by comparing it to full simulations of two popular modified gravity models, namely f ( R ) gravity and nDGP, and find good agreement in the modified gravity boost-factors relative to ΛCDM even when using a fairly small number of COLA time steps.

Evaluating the use of mobile phone technology to enhance cardiovascular disease screening by community health workers.

Science.gov (United States)

Surka, Sam; Edirippulige, Sisira; Steyn, Krisela; Gaziano, Thomas; Puoane, Thandi; Levitt, Naomi

2014-09-01

Primary prevention of cardiovascular disease (CVD),by identifying individuals at risk is a well-established, but costly strategy when based on measurements that depend on laboratory analyses. A non-laboratory, paper-based CVD risk assessment chart tool has previously been developed to make screening more affordable in developing countries. Task shifting to community health workers (CHWs) is being investigated to further scale CVD risk screening. This study aimed to develop a mobile phone CVD risk assessment application and to evaluate its impact on CHW training and the duration of screening for CVD in the community by CHWs. A feature phone application was developed using the open source online platform, CommCare(©). CHWs (n=24) were trained to use both paper-based and mobile phone CVD risk assessment tools. They were randomly allocated to using one of the risk tools to screen 10-20 community members and then crossed over to screen the same number, using the alternate risk tool. The impact on CHW training time, screening time and margin of error in calculating risk scores was recorded. A focus group discussion evaluated experiences of CHWs using the two tools. The training time was 12.3h for the paper-based chart tool and 3h for the mobile phone application. 537 people were screened. The mean screening time was 36 min (SD=12.6) using the paper-base chart tool and 21 min (SD=8.71) using the mobile phone application, p=mobile phone calculations were correct. Qualitative findings from the focus group discussion corresponded with the findings of the pilot study. The reduction in CHW training time, CVD risk screening time, lack of errors in calculation of a CVD risk score and end user satisfaction when using a mobile phone application, has implications in terms of adoption and sustainability of this primary prevention strategy to identify people with high CVD risk who can be referred for appropriate diagnoses and treatment. Copyright © 2014 Elsevier Ireland Ltd. All

Plasma screening effects on the energies of hydrogen atom

International Nuclear Information System (INIS)

Soylu, A.

2012-01-01

A more general exponential cosine screened Coulomb potential is used for the first time to investigate the screening effects on the hydrogen atom in plasmas. This potential is examined for four different cases that correspond to four different type potentials when the different parameters are used in the potential within the framework of the well-known asymptotic iteration method. By solving the corresponding the radial Schrödinger equation with the screened and exponential cosine screened Coulomb potentials and comparing the obtained energy eigenvalues with the results of other studies, the applicability of the method to this kind of plasma physics problem is shown. The energy values of more general exponential cosine screened Coulomb potential are presented for various parameters in the potential. One of the advantages of the present potential is that it exhibits stronger screening effect than that of the exponential cosine screened Coulomb potential and it is also reduced to screened Coulomb and exponential cosine screened Coulomb as well as Coulomb potentials for special values of parameters. The parameters in the potential would be useful to model screening effects which cause an increase or decrease in the energy values of hydrogen atom in both Debye and quantum plasmas and in this manner this potential would be useful for the investigations of the atomic structure and collisions in plasmas.

Analysis of previous screening examinations for patients with breast cancer

International Nuclear Information System (INIS)

Lee, Eun Hye; Cha, Joo Hee; Han, Dae Hee; Choi, Young Ho; Hwang, Ki Tae; Ryu, Dae Sik; Kwak, Jin Ho; Moon, Woo Kyung

2007-01-01

We wanted to improve the quality of subsequent screening by reviewing the previous screening of breast cancer patients. Twenty-four breast cancer patients who underwent previous screening were enrolled. All 24 took mammograms and 15 patients also took sonograms. We reviewed the screening retrospectively according to the BI-RADS criteria and we categorized the results into false negative, true negative, true positive and occult cancers. We also categorized the causes of false negative cancers into misperception, misinterpretation and technical factors and then we analyzed the attributing factors. Review of the previous screening revealed 66.7% (16/24) false negative, 25.0% (6/24) true negative, and 8.3% (2/24) true positive cancers. False negative cancers were caused by the mammogram in 56.3% (9/16) and by the sonogram in 43.7% (7/16). For the false negative cases, all of misperception were related with mammograms and this was attributed to dense breast, a lesion located at the edge of glandular tissue or the image, and findings seen on one view only. Almost all misinterpretations were related with sonograms and attributed to loose application of the final assessment. To improve the quality of breast screening, it is essential to overcome the main causes of false negative examinations, including misperception and misinterpretation. We need systematic education and strict application of final assessment categories of BI-RADS. For effective communication among physicians, it is also necessary to properly educate them about BI-RADS

Smart material screening machines using smart materials and controls

Science.gov (United States)

Allaei, Daryoush; Corradi, Gary; Waigand, Al

2002-07-01

The objective of this product is to address the specific need for improvements in the efficiency and effectiveness in physical separation technologies in the screening areas. Currently, the mining industry uses approximately 33 billion kW-hr per year, costing 1.65 billion dollars at 0.05 cents per kW-hr, of electrical energy for physical separations. Even though screening and size separations are not the single most energy intensive process in the mining industry, they are often the major bottleneck in the whole process. Improvements to this area offer tremendous potential in both energy savings and production improvements. Additionally, the vibrating screens used in the mining processing plants are the most costly areas from maintenance and worker health and safety point of views. The goal of this product is to reduce energy use in the screening and total processing areas. This goal is accomplished by developing an innovative screening machine based on smart materials and smart actuators, namely smart screen that uses advanced sensory system to continuously monitor the screening process and make appropriate adjustments to improve production. The theory behind the development of Smart Screen technology is based on two key technologies, namely smart actuators and smart Energy Flow ControlT (EFCT) strategies, developed initially for military applications. Smart Screen technology controls the flow of vibration energy and confines it to the screen rather than shaking much of the mass that makes up the conventional vibratory screening machine. Consequently, Smart Screens eliminates and downsizes many of the structural components associated with conventional vibratory screening machines. As a result, the surface area of the screen increases for a given envelope. This increase in usable screening surface area extends the life of the screens, reduces required maintenance by reducing the frequency of screen change-outs and improves throughput or productivity.

Mechanistic modeling for mammography screening risks

International Nuclear Information System (INIS)

Bijwaard, Harmen

2008-01-01

Full text: Western populations show a very high incidence of breast cancer and in many countries mammography screening programs have been set up for the early detection of these cancers. Through these programs large numbers of women (in the Netherlands, 700.000 per year) are exposed to low but not insignificant X-ray doses. ICRP based risk estimates indicate that the number of breast cancer casualties due to mammography screening can be as high as 50 in the Netherlands per year. The number of lives saved is estimated to be much higher, but for an accurate calculation of the benefits of screening a better estimate of these risks is indispensable. Here it is attempted to better quantify the radiological risks of mammography screening through the application of a biologically based model for breast tumor induction by X-rays. The model is applied to data obtained from the National Institutes of Health in the U.S. These concern epidemiological data of female TB patients who received high X-ray breast doses in the period 1930-1950 through frequent fluoroscopy of their lungs. The mechanistic model that is used to describe the increased breast cancer incidence is based on an earlier study by Moolgavkar et al. (1980), in which the natural background incidence of breast cancer was modeled. The model allows for a more sophisticated extrapolation of risks to the low dose X-ray exposures that are common in mammography screening and to the higher ages that are usually involved. Furthermore, it allows for risk transfer to other (non-western) populations. The results have implications for decisions on the frequency of screening, the number of mammograms taken at each screening, minimum and maximum ages for screening and the transfer to digital equipment. (author)

Determinants of successful implementation of population-based cancer screening programmes

DEFF Research Database (Denmark)

Lynge, Elsebeth; Törnberg, Sven; von Karsa, Lawrence

2012-01-01

consider when planning, implementing and running population based cancer screening programmes. The list is general and is applicable to breast, cervical and colorectal cancer screening. It is based on evidence presented in the three European Union guidelines on quality assurance in cancer screening...... and diagnosis, supplemented with other literature and expert experience presented at a European Science Advisory Network for Health workshop. The implementation of a cancer screening programme should be divided into the following seven phases: (1) before planning, (2) planning, (3) feasibility testing, (4......) piloting or trial implementation, (5) scaling up from pilot to service, (6) running of full-scale programme, and (7) sustainability. For each phase, a substantial number of specified conditions have to be met. Successful implementation of a cancer screening programme requires societal acceptance and local...

Approaches to virtual screening and screening library selection.

Science.gov (United States)

Wildman, Scott A

2013-01-01

The ease of access to virtual screening (VS) software in recent years has resulted in a large increase in literature reports. Over 300 publications in the last year report the use of virtual screening techniques to identify new chemical matter or present the development of new virtual screening techniques. The increased use is accompanied by a corresponding increase in misuse and misinterpretation of virtual screening results. This review aims to identify many of the common difficulties associated with virtual screening and allow researchers to better assess the reliability of their virtual screening effort.

The evolving role of new imaging methods in breast screening.

Science.gov (United States)

Houssami, Nehmat; Ciatto, Stefano

2011-09-01

The potential to avert breast cancer deaths through screening means that efforts continue to identify methods which may enhance early detection. While the role of most new imaging technologies remains in adjunct screening or in the work-up of mammography-detected abnormalities, some of the new breast imaging tests (such as MRI) have roles in screening groups of women defined by increased cancer risk. This paper highlights the evidence and the current role of new breast imaging technologies in screening, focusing on those that have broader application in population screening, including digital mammography, breast ultrasound in women with dense breasts, and computer-aided detection. It highlights that evidence on new imaging in screening comes mostly from non-randomised studies that have quantified test detection capability as adjunct to mammography, or have compared measures of screening performance for new technologies with that of conventional mammography. Two RCTs have provided high-quality evidence on the equivalence of digital and conventional mammography and on outcomes of screen-reading complemented by CAD. Many of these imaging technologies enhance cancer detection but also increase recall and false positives in screening. Copyright © 2011 Elsevier Inc. All rights reserved.

Disposable Screen Printed Electrochemical Sensors: Tools for Environmental Monitoring

Directory of Open Access Journals (Sweden)

Akhtar Hayat

2014-06-01

Full Text Available Screen printing technology is a widely used technique for the fabrication of electrochemical sensors. This methodology is likely to underpin the progressive drive towards miniaturized, sensitive and portable devices, and has already established its route from “lab-to-market” for a plethora of sensors. The application of these sensors for analysis of environmental samples has been the major focus of research in this field. As a consequence, this work will focus on recent important advances in the design and fabrication of disposable screen printed sensors for the electrochemical detection of environmental contaminants. Special emphasis is given on sensor fabrication methodology, operating details and performance characteristics for environmental applications.

An algorithm for computing screened Coulomb scattering in GEANT4

Energy Technology Data Exchange (ETDEWEB)

Mendenhall, Marcus H. [Vanderbilt University Free Electron Laser Center, P.O. Box 351816 Station B, Nashville, TN 37235-1816 (United States)]. E-mail: marcus.h.mendenhall@vanderbilt.edu; Weller, Robert A. [Department of Electrical Engineering and Computer Science, Vanderbilt University, P.O. Box 351821 Station B, Nashville, TN 37235-1821 (United States)]. E-mail: robert.a.weller@vanderbilt.edu

2005-01-01

An algorithm has been developed for the GEANT4 Monte-Carlo package for the efficient computation of screened Coulomb interatomic scattering. It explicitly integrates the classical equations of motion for scattering events, resulting in precise tracking of both the projectile and the recoil target nucleus. The algorithm permits the user to plug in an arbitrary screening function, such as Lens-Jensen screening, which is good for backscattering calculations, or Ziegler-Biersack-Littmark screening, which is good for nuclear straggling and implantation problems. This will allow many of the applications of the TRIM and SRIM codes to be extended into the much more general GEANT4 framework where nuclear and other effects can be included.

An algorithm for computing screened Coulomb scattering in GEANT4

International Nuclear Information System (INIS)

Mendenhall, Marcus H.; Weller, Robert A.

2005-01-01

An algorithm has been developed for the GEANT4 Monte-Carlo package for the efficient computation of screened Coulomb interatomic scattering. It explicitly integrates the classical equations of motion for scattering events, resulting in precise tracking of both the projectile and the recoil target nucleus. The algorithm permits the user to plug in an arbitrary screening function, such as Lens-Jensen screening, which is good for backscattering calculations, or Ziegler-Biersack-Littmark screening, which is good for nuclear straggling and implantation problems. This will allow many of the applications of the TRIM and SRIM codes to be extended into the much more general GEANT4 framework where nuclear and other effects can be included

BioCircos.js: an interactive Circos JavaScript library for biological data visualization on web applications.

Science.gov (United States)

Cui, Ya; Chen, Xiaowei; Luo, Huaxia; Fan, Zhen; Luo, Jianjun; He, Shunmin; Yue, Haiyan; Zhang, Peng; Chen, Runsheng

2016-06-01

We here present BioCircos.js, an interactive and lightweight JavaScript library especially for biological data interactive visualization. BioCircos.js facilitates the development of web-based applications for circular visualization of various biological data, such as genomic features, genetic variations, gene expression and biomolecular interactions. BioCircos.js and its manual are freely available online at http://bioinfo.ibp.ac.cn/biocircos/ rschen@ibp.ac.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Photochemical Screening and antimicrobial activity of zizyphus ...

African Journals Online (AJOL)

student

2012-03-13

Mar 13, 2012 ... chemical composition of essential oil of Pamburus missionis. J. Ethnopharmaco. 124(1): 151-153. Raman BV, Rao DN, Radhakrishnan TM (2007). Screening of medicinal plants for proteinaceous antibacterial compounds. In: Application of. Biotechnology-Medicinal plants and food processing. Souvenir,.

Machine learning in virtual screening.

Science.gov (United States)

Melville, James L; Burke, Edmund K; Hirst, Jonathan D

2009-05-01

In this review, we highlight recent applications of machine learning to virtual screening, focusing on the use of supervised techniques to train statistical learning algorithms to prioritize databases of molecules as active against a particular protein target. Both ligand-based similarity searching and structure-based docking have benefited from machine learning algorithms, including naïve Bayesian classifiers, support vector machines, neural networks, and decision trees, as well as more traditional regression techniques. Effective application of these methodologies requires an appreciation of data preparation, validation, optimization, and search methodologies, and we also survey developments in these areas.

High throughput label-free platform for statistical bio-molecular sensing

DEFF Research Database (Denmark)

Bosco, Filippo; Hwu, En-Te; Chen, Ching-Hsiu

2011-01-01

Sensors are crucial in many daily operations including security, environmental control, human diagnostics and patient monitoring. Screening and online monitoring require reliable and high-throughput sensing. We report on the demonstration of a high-throughput label-free sensor platform utilizing...

Fourier-transform infrared spectroscopy for rapid screening and live-cell monitoring: application to nanotoxicology.

Science.gov (United States)

Sundaram, S K; Sacksteder, Colette A; Weber, Thomas J; Riley, Brian J; Addleman, R Shane; Harrer, Bruce J; Peterman, John W

2013-01-01

A significant challenge to realize the full potential of nanotechnology for therapeutic and diagnostic applications is to understand and evaluate how live cells interact with an external stimulus, such as a nanosized particle, and the toxicity and broad risk associated with these stimuli. It is difficult to capture the complexity and dynamics of these interactions by following omics-based approaches exclusively, which can be expensive and time-consuming. Attenuated total reflectance-Fourier transform infrared spectroscopy is well suited to provide noninvasive live-cell monitoring of cellular responses to potentially toxic nanosized particles or other stimuli. This alternative approach provides the ability to carry out rapid toxicity screenings and nondisruptive monitoring of live-cell cultures. We review the technical basis of the approach, the instrument configuration and interface with the biological media, the various effects that impact the data, subsequent data analysis and toxicity, and present some preliminary results on live-cell monitoring.

Usability and Accessibility of eBay by Screen Reader

Science.gov (United States)

Buzzi, Maria Claudia; Buzzi, Marina; Leporini, Barbara; Akhter, Fahim

The evolution of Information and Communication Technology and the rapid growth of the Internet have fuelled a great diffusion of eCommerce websites. Usually these sites have complex layouts crowded with active elements, and thus are difficult to navigate via screen reader. Interactive environments should be properly designed and delivered to everyone, including the blind, who usually use screen readers to interact with their computers. In this paper we investigate the interaction of blind users with eBay, a popular eCommerce website, and discuss how using the W3C Accessible Rich Internet Applications (WAI-ARIA) suite could improve the user experience when navigating via screen reader.

Application of RetCamⅡ in the screening of neonatal fundus disease

Directory of Open Access Journals (Sweden)

Zhi-Gang Xiao

2013-08-01

Full Text Available AIM: To investigate the safe and reliable examination method for neonatal fundus screening.METHODS: Fundus information of 2 836 neonates performed by RetCamⅡ in our hospital from January 1, 2012 to December 31, 2012 were retrospectively analyzed, including 1 625 cases(57.30%of premature infants which were first examined 1-4 weeks after birth and 1 211 cases(42.70%of term infants which were first examined within 4 weeks after birth.RESULTS: Totally 454 cases of abnormalfundus were found, including 207 cases(12.74%of retinopathy of prematurity(ROP, ROPⅠ in 118 cases(57%, ROPⅡ in 58 cases(28.02%, ROPⅢ in 23 cases(11.11%, ROPⅣ in 8 cases(3.86%, no case of ROPV. A total of 247(20.40%term infants had abnormal fundus, of which 68 cases(27.53%were developmental or hereditary disease, retinoblastoma in 1 case(0.40%, retinal hemorrhage in 102 cases(41.30%, retinal exudative changes in 68 cases(27.53%, optic atrophy in 5 cases(2.02%and optic disc edema in 3 cases(1.21%.CONCLUSION: Neonatal fundus diseases were so various and harmful that early screening should be attended to. Premature infants and term infants with high risk are treated as focus group of fundus screening and RetCamII examination is safe and effective.

Population newborn screening for inherited metabolic disease: current UK perspectives.

Science.gov (United States)

Green, A; Pollitt, R J

1999-06-01

Some of the generally accepted criteria for screening programmes are inappropriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application of such criteria creates special difficulties for screening by tandem mass spectrometry, which can detect a range diseases with widely different natural histories and responsiveness to treatment. Further difficulties arise from increasing demands for direct proof of the effects of screening on long-term morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossible to achieve for such relatively rare diseases. This approach also oversimplifies the complex matrix of costs and benefits of newborn metabolic screening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot studies of screening with existing experience of the natural history, diagnosis, and management of the individual disorders concerned.

Touch Screen Tablets and Emergent Literacy

Science.gov (United States)

Neumann, Michelle M.; Neumann, David L.

2014-01-01

The use of touch screen tablets by young children is increasing in the home and in early childhood settings. The simple tactile interface and finger-based operating features of tablets may facilitate preschoolers' use of tablet application software and support their educational development in domains such as literacy. This article reviews…

Interactive Screen Experiments with Single Photons

Science.gov (United States)

Bronner, Patrick; Strunz, Andreas; Silberhorn, Christine; Meyn, Jan-Peter

2009-01-01

Single photons are used for fundamental quantum physics experiments as well as for applications. Originally being a topic of advance courses, such experiments are increasingly a subject of undergraduate courses. We provide interactive screen experiments (ISE) for supporting the work in a real laboratory, and for students who do not have access to…

Primary care colorectal cancer screening correlates with breast cancer screening: implications for colorectal cancer screening improvement interventions.

Science.gov (United States)

Weiss, Jennifer M; Pandhi, Nancy; Kraft, Sally; Potvien, Aaron; Carayon, Pascale; Smith, Maureen A

2018-04-25

National colorectal cancer (CRC) screening rates have plateaued. To optimize interventions targeting those unscreened, a better understanding is needed of how this preventive service fits in with multiple preventive and chronic care needs managed by primary care providers (PCPs). This study examines whether PCP practices of other preventive and chronic care needs correlate with CRC screening. We performed a retrospective cohort study of 90 PCPs and 33,137 CRC screening-eligible patients. Five PCP quality metrics (breast cancer screening, cervical cancer screening, HgbA1c and LDL testing, and blood pressure control) were measured. A baseline correlation test was performed between these metrics and PCP CRC screening rates. Multivariable logistic regression with clustering at the clinic-level estimated odds ratios and 95% confidence intervals for these PCP quality metrics, patient and PCP characteristics, and their relationship to CRC screening. PCP CRC screening rates have a strong correlation with breast cancer screening rates (r = 0.7414, p < 0.001) and a weak correlation with the other quality metrics. In the final adjusted model, the only PCP quality metric that significantly predicted CRC screening was breast cancer screening (OR 1.25; 95% CI 1.11-1.42; p < 0.001). PCP CRC screening rates are highly concordant with breast cancer screening. CRC screening is weakly concordant with cervical cancer screening and chronic disease management metrics. Efforts targeting PCPs to increase CRC screening rates could be bundled with breast cancer screening improvement interventions to increase their impact and success.

More comprehensive discussion of CRC screening associated with higher screening.

Science.gov (United States)

Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

2013-04-01

Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

High content screening in microfluidic devices

Science.gov (United States)

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2011-01-01

Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

Large-screen display industry: market and technology trends for direct view and projection displays

Science.gov (United States)

Castellano, Joseph A.; Mentley, David E.

1996-03-01

Large screen information displays are defined as dynamic electronic displays that can be viewed by more than one person and are at least 2-feet wide. These large area displays for public viewing provide convenience, entertainment, security, and efficiency to the viewers. There are numerous uses for large screen information displays including those in advertising, transportation, traffic control, conference room presentations, computer aided design, banking, and military command/control. A noticeable characteristic of the large screen display market is the interchangeability of display types. For any given application, the user can usually choose from at least three alternative technologies, and sometimes from many more. Some display types have features that make them suitable for specific applications due to temperature, brightness, power consumption, or other such characteristic. The overall worldwide unit consumption of large screen information displays of all types and for all applications (excluding consumer TV) will increase from 401,109 units in 1995 to 655,797 units in 2002. On a unit consumption basis, applications in business and education represent the largest share of unit consumption over this time period; in 1995, this application represented 69.7% of the total. The market (value of shipments) will grow from DOL3.1 billion in 1995 to DOL3.9 billion in 2002. The market will be dominated by front LCD projectors and LCD overhead projector plates.

Small-Angle X-ray Scattering Screening Complements Conventional Biophysical Analysis

DEFF Research Database (Denmark)

Tian, Xinsheng; Langkilde, Annette Eva; Thorolfsson, Matthias

2014-01-01

A crucial step in the development of therapeutic monoclonal antibodies is the selection of robust pharmaceutical candidates and screening of efficacious protein formulations to increase the resistance toward physicochemical degradation and aggregation during processing and storage. Here, we intro...... application of extensive SAXS screening in antibody selection, eventual engineering, and formulation development. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci....

The Systematic Screening Methodology for Surfactant Flooding Chemicals in Enhanced Oil Recovery

DEFF Research Database (Denmark)

Cholpraves, Cholathis; Rattanaudom, Pattamas; Suriyapraphadilok, Uthaiporn

2017-01-01

for non-ionic surfactants is found to be qualitatively correct and so it can be used for surfactant screening-selection. Other properties like melting point, cloud-point, etc., are also used for the screening-selection step. Application of the model-based method is highlighted through two case studies...

Non‐invasive prenatal screening for chromosomal abnormalities ...

African Journals Online (AJOL)

Non‐invasive prenatal screening for chromosomal abnormalities using circulating cell-free fetal DNA in maternal plasma: Current applications, limitations and ... fetal DNAtesting is a matter of concern, because of the low positive predictive value for these changes, and the associated significant cumulative false-positive rate.

Screening of complex thermophilic microbial community and ...

African Journals Online (AJOL)

Screening of complex thermophilic microbial community and application during municipal solid waste aerobic composting. ... African Journal of Biotechnology ... Complex microbial community HP83 and HC181 were applied during municipal solid waste aerobic composting that was carried out in a composting reactor under ...

Barcoded microchips for biomolecular assays.

Science.gov (United States)

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

2015-01-20

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

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

Science.gov (United States)

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

2012-07-01

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

Quinone-Based Polymers for Label-Free and Reagentless Electrochemical Immunosensors: Application to Proteins, Antibodies and Pesticides Detection

Directory of Open Access Journals (Sweden)

Minh-Chau Pham

2013-01-01

Full Text Available Polyquinone derivatives are widely recognized in the literature for their remarkable properties, their biocompatibility, simple synthesis, and easy bio-functionalization. We have shown that polyquinones present very stable electroactivity in neutral aqueous medium within the cathodic potential domain avoiding side oxidation of interfering species. Besides, they can act as immobilized redox transducers for probing biomolecular interactions in sensors. Our group has been working on devices based on such modified electrodes with a view to applications for proteins, antibodies and organic pollutants using a reagentless label-free electrochemical immunosensor format. Herein, these developments are briefly reviewed and put into perspective.

Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens

DEFF Research Database (Denmark)

Timms, Richard T.; Menzies, Sam A.; Tchasovnikarova, Iva A.

2016-01-01

The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we...... compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing ‘gold standard’ method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum....../3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox....

Interfacing of DNA with carbon nanotubes for nanodevice applications

Energy Technology Data Exchange (ETDEWEB)

Rastogi, Richa, E-mail: richa.bend@gmail.com [Biomolecular Electronics and Nanotechnology Division (BEND), Central Scientific Instruments Organisation (CSIO), Sector-30C, Chandigarh 160030 (India); Centre of Advanced Studies in Physics, Punjab University, Sector-14, Chandigarh 160014 (India); Dhindsa, Navneet [Biomolecular Electronics and Nanotechnology Division (BEND), Central Scientific Instruments Organisation (CSIO), Sector-30C, Chandigarh 160030 (India); Suri, C. Raman [Biosensor Division, Institute of Microbial Technology (IMTECH), Sector-39, Chandigarh 160039 (India); Pant, B.D. [Central Electronics Engineering Research Institute, Pilani, Rajasthan (India); Tripathi, S.K. [Centre of Advanced Studies in Physics, Punjab University, Sector-14, Chandigarh 160014 (India); Kaur, Inderpreet; Bharadwaj, Lalit M. [Biomolecular Electronics and Nanotechnology Division (BEND), Central Scientific Instruments Organisation (CSIO), Sector-30C, Chandigarh 160030 (India)

2012-08-15

In nanotechnology, carbon nanotubes are evolving as 'hot spot' due to their applications as most sensitive biosensors. Thus, study of effect of biomolecular interaction is prerequisite for their electrical application in biosensors and bioelectronics. Here, we have explored this effect on electrical properties of carbon nanotubes with DNA as a model biomolecule. A stable conjugate of carbon nanotubes with DNA is formed via covalent methodology employing quantum dot as fluoropore and characterized with various spectroscopic, fluoroscopic and microscopic techniques. CNT-DNA adduct showed decreased transconductance (from 614.46 {mu}S to 1.34 {mu}S) and shift of threshold voltage (from -0.85 V to 2.5 V) due to change in Schottky barriers at metal-nanotube contact. In addition, decrease in hole mobility (from 4.46 Multiplication-Sign 10{sup 6} to 9.72 Multiplication-Sign 10{sup 3} cm{sup 2} V{sup -1} s{sup -1}) and increase in ON-linear resistance (from 74 k Ohm-Sign to 0.44 M Ohm-Sign ) conclude large change in device parameters. On the one hand, this substantial change in device parameters after interfacing with biomolecules supports application of carbon nanotubes in the field of biosensors while on the other hand, the same can limit their use in future power electronic devices where stability in device parameters is essential. -- Graphical abstract: Carbon nanotubes are interfaced with DNA via covalent interactions and characterized with spectroscopic, fluoroscopic and microscopic techniques. Electrical characterization of this stable SWNT-DNA conjugate shows decreased transconductance and shift of threshold voltage towards positive gate voltages. On the one hand, this substantial change in device parameters after interfacing with biomolecules supports application of carbon nanotubes in the field of biosensors while on the other hand, the same can limit their use in future power electronic devices where stability in device parameters is essential

Qualitative vs. quantitative data: Controls on the accuracy of PID field screening in petroleum contamination assessment applications

International Nuclear Information System (INIS)

Luessen, M.J.; Allex, M.K.; Holzel, F.R.

1995-01-01

The use of photoionization detectors (PIDs) for field screening of soils for volatile organic contaminants has become a standard industry practice. PID screening data is generally utilized as a qualitative basis for selection of samples for laboratory analysis to quantify concentrations of specific contaminants of concern. Both qualitative field screening data and quantitative laboratory analytical data were reviewed for more than 100 hydrogeologic assessment sites in Ohio to evaluate controls on the effectiveness of field screening data. Assessment data evaluated was limited to sites at which the suspected contaminant source was a gasoline underground storage tanks system. In each case, a 10.0 eV (or greater) PID calibrated for benzene was used to screen soils which were analyzed for benzene, toluene, ethylbenzene and xylene (BTEX) by SW 846 method 8020. Controls on field screening which were evaluated for each site included (1) soil classification, (2) soil moisture, (3) weather conditions, (4) background levels, (5) equipment quality, (6) screening methodology, and (7) laboratory QA/QC. Statistical data analysis predictably indicated a general overestimate of total BTEX levels based on field screening (gasoline is approximately 25 weight percent BTEX). However, data locally indicated cases of both significant (i.e., more than an order of magnitude difference) over- and under-estimation of actual BTEX concentrations (i.e., quantitative laboratory data) by field screening data

Suicide Risk Screening Tools and the Youth Population.

Science.gov (United States)

Patterson, Sharon

2016-08-01

The use of suicide risk screening tools is a critical component of a comprehensive approach to suicide risk assessment. Since nurses frequently spend more time with patients than any other healthcare professional, they are in key positions to detect and prevent suicidal behavior in youth. To inform nurses about suicide risk screening tools for the youth population. Suicide risk screening tools are research-based standardized instruments that are used to identify people who may be at risk for suicide. A literature search was performed using the Athabasca University Library Resource, the databases of the Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, and Google Scholar. Nurses are cautioned to utilize suicide risk screening tools as only part of the suicide risk assessment in youth populations and avoid the danger of relying on tools that may result in a blind application of evidence to the detriment of clinical experience and judgement. © 2016 Wiley Periodicals, Inc.

Hot Topic: Preimplantation aneuploidy screening

Directory of Open Access Journals (Sweden)

Kayhan Yakın

2009-03-01

Full Text Available Preimplantation Genetic Screening (PGS is a technique that has been introduced into clinical practice to screen and eliminate aneuploid embryos form transfer with the intention to improve implantation rates and decrease pregnancy wastage. Although practiced widely throughout the world the PGS unfortunately has been adopted without being subjected to rigorous scientific validation. Data from recent prospective randomized trials have shed doubt on the efficacy of the procedure when used in women with advanced age, one of the target populations for PGS. Other purported indications for the application of this complicated technique such as recurrent implantation failure and recurrent spontaneous abortion have not been subjected to randomized controlled trials. For the best interest of patients, we feel it is timely for a debate regarding the efficacy and safety of PGS.

The screening effects of the screened exchange hybrid functional in surface systems: A case study on the CO/Pt(111) problem

Energy Technology Data Exchange (ETDEWEB)

Li, H., E-mail: li-huanglong@mail.tsinghua.edu.cn [Department of Precision Instrument, Tsinghua University, Beijing, 100084 (China); Gillen, R. [Institut für Festkörperphysik. Technische Universität Berlin. Hardenbergstr. 36, 10623 Berlin (Germany); Robertson, J., E-mail: jr214@cam.ac.uk [Engineering Department, University of Cambridge, Cambridge CB2 1PZ (United Kingdom)

2016-06-15

The screened exchange (sX) hybrid functional has been widely used in computational material science. Although it has widely been studied in bulk systems, less is known about its functional behavior in surface systems which are crucial to many technologies such as materials synthesis and nano-electronic devices. Assessing the screening dependent functional behaviors in the surface systems is therefore important for its application in such systems. In this work, we investigate the screening effects of the sX in CO adsorption on Pt(111) surface. The differences between the sX and Heyd-Scuseria-Ernzerhof (HSE06) hybrid functionals, and the effects of screening parameters are studied. The screening has two effects: first, the HOMO-LUMO gap is screening dependent. This affects the site preference most significantly. In this work, atop adsorption of CO/Pt(111) is predicted by the hybrid functionals with screened exchange potential. The sX(1.44) gives the largest HOMO-LUMO gap for the isolated CO molecule. The adsorption energy difference between the atop and fcc site is also the largest by the sX(1.44) which is explained by the reduced metal d states to the CO 2π* state back-donation, with stronger effect for the fcc adsorption than for the atop adsorption; second, the adsorption energy is screening dependent. This can be seen by comparing the sX(2.38) and HSE06 which have different screening strengths. They show similar surface band structures for the CO adsorption but different adsorption energies, which is explained by the stronger CO 5σ state to the metal d states donation or the effectively screened Pauli repulsion. This work underlines the screening strength as a main difference between sX and HSE06, as well as an important hybrid functional parameter for surface calculation.

Smartphone-Based Hearing Screening in Noisy Environments

Directory of Open Access Journals (Sweden)

Youngmin Na

2014-06-01

Full Text Available It is important and recommended to detect hearing loss as soon as possible. If it is found early, proper treatment may help improve hearing and reduce the negative consequences of hearing loss. In this study, we developed smartphone-based hearing screening methods that can ubiquitously test hearing. However, environmental noise generally results in the loss of ear sensitivity, which causes a hearing threshold shift (HTS. To overcome this limitation in the hearing screening location, we developed a correction algorithm to reduce the HTS effect. A built-in microphone and headphone were calibrated to provide the standard units of measure. The HTSs in the presence of either white or babble noise were systematically investigated to determine the mean HTS as a function of noise level. When the hearing screening application runs, the smartphone automatically measures the environmental noise and provides the HTS value to correct the hearing threshold. A comparison to pure tone audiometry shows that this hearing screening method in the presence of noise could closely estimate the hearing threshold. We expect that the proposed ubiquitous hearing test method could be used as a simple hearing screening tool and could alert the user if they suffer from hearing loss.

The techniques of aestheticization of screen violence

Directory of Open Access Journals (Sweden)

Eugene V. Plyusnin

2016-02-01

Full Text Available The relevance of the topic is defined to variety of spectacular images of violence on the screen, and insufficient knowledge of the problems in the Ukrainian scientific discourse. Touching the information space, individuals are inevitably faced with a variety of images of violence. In the process of reception of screen images of cruelty to the fore entertainment and attraction of external form. As a rule, the desire for violence negates aesthetization images in the minds of the moral imperatives of the viewer and removes the visual taboo. The violence is so widespread in modern screens, acquires special importance, providing a strong emotional impact on the viewer. The author carried out serious work on the study of various theoretical approaches to the study of on-screen violence. In the article the basic definitions and distinguishing features are marked on-screen violence. On the basis of the qualitative content analysis of audiovisual documents and focused interviews highlighted four ways aestheticization of violence: romantization, carnivalization, absurdization and uglytizatio. They are clearly seen in the structure of genre cinema and practically applicable in the author’s cinema due to the uniqueness of narrative line and the realization of personal intentions of the director, who find themselves outside the genre cliches.

An Algorithm for Glaucoma Screening in Clinical Settings and Its Preliminary Performance Profile

Directory of Open Access Journals (Sweden)

S-Farzad Mohammadi

2013-01-01

Full Text Available Purpose: To devise and evaluate a screening algorithm for glaucoma in clinical settings. Methods: Screening included examination of the optic disc for vertical cupping (≥0.4 and asymmetry (≥0.15, Goldmann applanation tonometry (≥21 mmHg, adjusted or unadjusted for central corneal thickness, and automated perimetry. In the diagnostic step, retinal nerve fiber layer imaging was performed using scanning laser polarimetry. Performance of the screening protocol was assessed in an eye hospital-based program in which 124 non-physician personnel aged 40 years or above were examined. A single ophthalmologist carried out the examinations and in equivocal cases, a glaucoma subspecialist′s opinion was sought. Results: Glaucoma was diagnosed in six cases (prevalence 4.8%; 95% confidence interval, 0.01-0.09 of whom five were new. The likelihood of making a definite diagnosis of glaucoma for those who were screened positively was 8.5 times higher than the estimated baseline risk for the reference population; the positive predictive value of the screening protocol was 30%. Screening excluded 80% of the initial population. Conclusion: Application of a formal screening protocol (such as our algorithm or its equivalent in clinical settings can be helpful in detecting new cases of glaucoma. Preliminary performance assessment of the algorithm showed its applicability and effectiveness in detecting glaucoma among subjects without any visual complaint.

Automated toxicological screening reports of modified Agilent MSD Chemstation combined with Microsoft Visual Basic application programs.

Science.gov (United States)

Choe, Sanggil; Kim, Suncheun; Choi, Hyeyoung; Choi, Hwakyoung; Chung, Heesun; Hwang, Bangyeon

2010-06-15

Agilent GC-MS MSD Chemstation offers automated library search report for toxicological screening using total ion chromatogram (TIC) and mass spectroscopy in normal mode. Numerous peaks appear in the chromatogram of biological specimen such as blood or urine and often large migrating peaks obscure small target peaks, in addition, any target peaks of low abundance regularly give wrong library search result or low matching score. As a result, retention time and mass spectrum of all the peaks in the chromatogram have to be checked to see if they are relevant. These repeated actions are very tedious and time-consuming to toxicologists. MSD Chemstation software operates using a number of macro files which give commands and instructions on how to work on and extract data from the chromatogram and spectroscopy. These macro files are developed by the own compiler of the software. All the original macro files can be modified and new macro files can be added to the original software by users. To get more accurate results with more convenient method and to save time for data analysis, we developed new macro files for reports generation and inserted new menus in the Enhanced Data Analysis program. Toxicological screening reports generated by these new macro files are in text mode or graphic mode and these reports can be generated with three different automated subtraction options. Text reports have Brief mode and Full mode and graphic reports have the option with or without mass spectrum mode. Matched mass spectrum and matching score for detected compounds are printed in reports by modified library searching modules. We have also developed an independent application program named DrugMan. This program manages drug groups, lists and parameters that are in use in MSD Chemstation. The incorporation of DrugMan with modified macro modules provides a powerful tool for toxicological screening and save a lot of valuable time on toxicological work. (c) 2010 Elsevier Ireland Ltd. All

[Screening of adverse childhood experiences in preschoolers: scoping review].

Science.gov (United States)

Vega-Arce, Maribel; Núñez-Ulloa, Gastón

The aim of the present article was to describe available scientific publications detailing strategies and screening tools for Adverse Childhood Experiences in preschoolers (2 to 5 years of age). A scoping review of the topic was carried out through investigative articles published in peer review journals from January 1998 to June 2017 and indexed in seven international databases (Cochrane Library, EBSCO, PubMed, Science Direct, Springer, Web of Science and Scielo). The articles were selected based on predefined criteria, using limiters and manual screening. Twenty articles published between 1999 and 2017 were selected. The screening of adverse childhood experiences is performed through opportunistic recruitment in a professional context aimed at caregivers and children, which integrates training actions, application of screening tools and reception of identified cases. Screening tools differ between interviews and questionnaires. Furthermore, we report the periodicity of the screening, the behaviors and beliefs of the professionals against it and the barriers to its implementation. This review confirms that the screening of Adverse Childhood Experiences is an emerging topic in the research field. We emphasize the need to systematize and evaluate the strategies and tools for screening Adverse Childhood Experiences, as well as to develop local approaches to respond to the needs of children exposed to adversity. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease.

Science.gov (United States)

Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

2010-12-14

The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of these cells including disease modeling, drug toxicity screening/drug discovery, gene therapy and cell replacement therapy.

Colon cancer screening

Science.gov (United States)

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

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)

Screening fifth forces in k-essence and DBI models

Energy Technology Data Exchange (ETDEWEB)

Brax, Philippe [Institut de Physique Théorique, CEA, IPhT, CNRS, URA2306, F-91191 Gif-sur-Yvette cédex (France); Burrage, Clare [School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD (United Kingdom); Davis, Anne-Christine, E-mail: Philippe.Brax@cea.fr, E-mail: Clare.Burrage@nottingham.ac.uk, E-mail: A.C.Davis@damtp.cam.ac.uk [Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, Cambridge CB3 0WA (United Kingdom)

2013-01-01

New fifth forces have not yet been detected in the laboratory or in the solar system, hence it is typically difficult to introduce new light scalar fields that would mediate such forces. In recent years it has been shown that a number of non-linear scalar field theories allow for a dynamical mechanism, such as the Vainshtein and chameleon ones, that suppresses the strength of the scalar fifth force in experimental environments. This is known as screening, however it is unclear how common screening is within non-linear scalar field theories. k-essence models are commonly studied examples of non-linear models, with DBI as the best motivated example, and so we ask whether these non-linearities are able to screen a scalar fifth force. We find that a Vainshtein-like screening mechanism exists for such models although with limited applicability. For instance, we cannot find a screening mechanism for DBI models. On the other hand, we construct a large class of k-essence models which lead to the acceleration of the Universe in the recent past for which the fifth force mediated by the scalar can be screened.

Introducing a open-quote modular close-quote approach to fish screen installation

International Nuclear Information System (INIS)

Taft, E.P.; Winchell, F.C.; Cook, T.C.; Sullivan, C.W.

1992-01-01

A new fish screen design-the modular inclined screen-promises to offer a versatile and cost-effective solution for fish protection in many situation. In an effort to provide the hydroelectric industry with more cost-effective alternatives to existing fish screen designs, the Electric Power Research Institute (EPRI) recently has undertaken several research projects. One focus of EPRI's research has been on the development and testing of high-velocity fish screens. This program has led to the development of a new screening concept, which shows promise for providing effective protection for a wide range of fish species at hydro plants, steam generating facilities, and irrigation diversions. The concept, known as the Modular Inclined Screen (MIS), currently is being evaluated in laboratory studies prior to field application. The screen is of open-quotes modularclose quotes design so as to provide the flexibility necessary for application at a broad range of water intakes. The module is suitable for installation in penstocks, canals, and head pond intakes. The MIS module consists of an entrance with a trashrack, dewatering stoplog slots, an inclined wedgewire screen set at a shallow angle of 10 to 20 degrees to the flow, and a bypass for diverting fish to a transport pipe. The screen is mounted on a pivot shaft so that it can be cleaned via rotation and backflushing. The module is completely enclosed, and is designed to operate at water velocities ranging from 2 to 10 feet per second depending on the fish species and life stages to be protected. Laboratory studies are under way to evaluate the design configuration that yields the best hydraulic conditions for safe fish passage, and the biological effectiveness of this design in diverting selected fish species to the bypass

Performance of the flow cytometric E-screen assay in screening estrogenicity of pure compounds and environmental samples

Energy Technology Data Exchange (ETDEWEB)

Vanparys, Caroline, E-mail: caroline.vanparys@ua.ac.be [Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp (Belgium); Depiereux, Sophie; Nadzialek, Stephanie [Research Unit in Organismal Biology (URBO), University of Namur (FUNDP), Namur (Belgium); Robbens, Johan; Blust, Ronny [Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp (Belgium); Kestemont, Patrick [Research Unit in Organismal Biology (URBO), University of Namur (FUNDP), Namur (Belgium); De Coen, Wim [Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp (Belgium); European Chemicals Agency (ECHA), Helsinki (Finland)

2010-09-15

In vitro estrogenicity screens are believed to provide a first prioritization step in hazard characterization of endocrine disrupting chemicals. When applied to complex environmental matrices or mixture samples, they have been indicated valuable in estimating the overall estrogen-mimicking load. In this study, the performance of an adapted format of the classical E-screen or MCF-7 cell proliferation assay was profoundly evaluated to rank pure compounds as well as influents and effluents of sewage treatment plants (STPs) according to estrogenic activity. In this adapted format, flow cytometric cell cycle analysis was used to allow evaluation of the MCF-7 cell proliferative effects after only 24 h of exposure. With an average EC{sub 50} value of 2 pM and CV of 22%, this assay appears as a sensitive and reproducible system for evaluation of estrogenic activity. Moreover, estrogenic responses of 17 pure compounds corresponded well, qualitatively and quantitatively, with other in vitro and in vivo estrogenicity screens, such as the classical E-screen (R{sup 2} = 0.98), the estrogen receptor (ER) binding (R{sup 2} = 0.84) and the ER transcription activation assay (R{sup 2} = 0.87). To evaluate the applicability of this assay for complex samples, influents and effluents of 10 STPs covering different treatment processes, were compared and ranked according to estrogenic removal efficiencies. Activated sludge treatment with phosphorus and nitrogen removal appeared most effective in eliminating estrogenic activity, followed by activated sludge, lagoon and filter bed. This is well in agreement with previous findings based on chemical analysis or biological activity screens. Moreover, ER blocking experiments indicated that cell proliferative responses were mainly ER mediated, illustrating that the complexity of the end point, cell proliferation, compared to other ER screens, does not hamper the interpretation of the results. Therefore, this study, among other E-screen studies

Performance of the flow cytometric E-screen assay in screening estrogenicity of pure compounds and environmental samples

International Nuclear Information System (INIS)

Vanparys, Caroline; Depiereux, Sophie; Nadzialek, Stephanie; Robbens, Johan; Blust, Ronny; Kestemont, Patrick; De Coen, Wim

2010-01-01

In vitro estrogenicity screens are believed to provide a first prioritization step in hazard characterization of endocrine disrupting chemicals. When applied to complex environmental matrices or mixture samples, they have been indicated valuable in estimating the overall estrogen-mimicking load. In this study, the performance of an adapted format of the classical E-screen or MCF-7 cell proliferation assay was profoundly evaluated to rank pure compounds as well as influents and effluents of sewage treatment plants (STPs) according to estrogenic activity. In this adapted format, flow cytometric cell cycle analysis was used to allow evaluation of the MCF-7 cell proliferative effects after only 24 h of exposure. With an average EC 50 value of 2 pM and CV of 22%, this assay appears as a sensitive and reproducible system for evaluation of estrogenic activity. Moreover, estrogenic responses of 17 pure compounds corresponded well, qualitatively and quantitatively, with other in vitro and in vivo estrogenicity screens, such as the classical E-screen (R 2 = 0.98), the estrogen receptor (ER) binding (R 2 = 0.84) and the ER transcription activation assay (R 2 = 0.87). To evaluate the applicability of this assay for complex samples, influents and effluents of 10 STPs covering different treatment processes, were compared and ranked according to estrogenic removal efficiencies. Activated sludge treatment with phosphorus and nitrogen removal appeared most effective in eliminating estrogenic activity, followed by activated sludge, lagoon and filter bed. This is well in agreement with previous findings based on chemical analysis or biological activity screens. Moreover, ER blocking experiments indicated that cell proliferative responses were mainly ER mediated, illustrating that the complexity of the end point, cell proliferation, compared to other ER screens, does not hamper the interpretation of the results. Therefore, this study, among other E-screen studies, supports the use of

Development of novel vaccines using DNA shuffling and screening strategies.

Science.gov (United States)

Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha

2004-02-01

DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.

Mathematic model analysis of Gaussian beam propagation through an arbitrary thickness random phase screen.

Science.gov (United States)

Tian, Yuzhen; Guo, Jin; Wang, Rui; Wang, Tingfeng

2011-09-12

In order to research the statistical properties of Gaussian beam propagation through an arbitrary thickness random phase screen for adaptive optics and laser communication application in the laboratory, we establish mathematic models of statistical quantities, which are based on the Rytov method and the thin phase screen model, involved in the propagation process. And the analytic results are developed for an arbitrary thickness phase screen based on the Kolmogorov power spectrum. The comparison between the arbitrary thickness phase screen and the thin phase screen shows that it is more suitable for our results to describe the generalized case, especially the scintillation index.

Depression Screening Using Daily Mental-Health Ratings from a Smartphone Application for Breast Cancer Patients.

Science.gov (United States)

Kim, Junetae; Lim, Sanghee; Min, Yul Ha; Shin, Yong-Wook; Lee, Byungtae; Sohn, Guiyun; Jung, Kyung Hae; Lee, Jae-Ho; Son, Byung Ho; Ahn, Sei Hyun; Shin, Soo-Yong; Lee, Jong Won

2016-08-04

Mobile mental-health trackers are mobile phone apps that gather self-reported mental-health ratings from users. They have received great attention from clinicians as tools to screen for depression in individual patients. While several apps that ask simple questions using face emoticons have been developed, there has been no study examining the validity of their screening performance. In this study, we (1) evaluate the potential of a mobile mental-health tracker that uses three daily mental-health ratings (sleep satisfaction, mood, and anxiety) as indicators for depression, (2) discuss three approaches to data processing (ratio, average, and frequency) for generating indicator variables, and (3) examine the impact of adherence on reporting using a mobile mental-health tracker and accuracy in depression screening. We analyzed 5792 sets of daily mental-health ratings collected from 78 breast cancer patients over a 48-week period. Using the Patient Health Questionnaire-9 (PHQ-9) as the measure of true depression status, we conducted a random-effect logistic panel regression and receiver operating characteristic (ROC) analysis to evaluate the screening performance of the mobile mental-health tracker. In addition, we classified patients into two subgroups based on their adherence level (higher adherence and lower adherence) using a k-means clustering algorithm and compared the screening accuracy between the two groups. With the ratio approach, the area under the ROC curve (AUC) is 0.8012, indicating that the performance of depression screening using daily mental-health ratings gathered via mobile mental-health trackers is comparable to the results of PHQ-9 tests. Also, the AUC is significantly higher (P=.002) for the higher adherence group (AUC=0.8524) than for the lower adherence group (AUC=0.7234). This result shows that adherence to self-reporting is associated with a higher accuracy of depression screening. Our results support the potential of a mobile mental

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