WorldWideScience

Sample records for biomolecular screening applications

  1. Application of Nanodiamonds in Biomolecular Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Ping Cheng

    2010-03-01

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

  2. Application of biomolecular recognition via magnetic nanoparticle in nanobiotechnology

    Science.gov (United States)

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

    2018-05-01

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

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

    Science.gov (United States)

    Turcatti, Gerardo

    2014-05-01

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

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

    Science.gov (United States)

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

    2012-04-01

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

  5. Biomolecular logic systems: applications to biosensors and bioactuators

    Science.gov (United States)

    Katz, Evgeny

    2014-05-01

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

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

    Science.gov (United States)

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

    2013-12-15

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

  7. 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.

  8. 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.

  9. 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...

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

    International Nuclear Information System (INIS)

    Zhou Pei; Wagner, Gerhard

    2010-01-01

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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Biomolecular EPR spectroscopy

    CERN Document Server

    Hagen, Wilfred Raymond

    2008-01-01

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

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

    International Nuclear Information System (INIS)

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

    1994-12-01

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

  18. 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.

  19. Conducting polymer based biomolecular electronic devices

    Indian Academy of Sciences (India)

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

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

    Directory of Open Access Journals (Sweden)

    Francesca Spyrakis

    2016-10-01

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

  1. 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

  2. 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.

  3. Biomolecular Science (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2012-04-01

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

  4. Prediction of Biomolecular Complexes

    KAUST Repository

    Vangone, Anna

    2017-04-12

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

  5. Prediction of Biomolecular Complexes

    KAUST Repository

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

    2017-01-01

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

  6. Biomolecular engineering for nanobio/bionanotechnology

    Science.gov (United States)

    Nagamune, Teruyuki

    2017-04-01

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

  7. Programming in biomolecular computation

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  8. Biomolecular Sciences: uniting Biology and Chemistry

    NARCIS (Netherlands)

    Vrieling, Engel

    2017-01-01

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

  9. 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.

  10. 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

  11. NMRbox: A Resource for Biomolecular NMR Computation.

    Science.gov (United States)

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

    2017-04-25

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

  12. Titanium dioxide as chemo-affinity chromatographic sorbent of biomolecular compounds - Applications in acidic modification-specific proteomics

    DEFF Research Database (Denmark)

    Engholm-Keller, Kasper; Larsen, Martin R

    2011-01-01

    biomolecules due to its unique ion and ligand exchange properties and high stability towards pH and temperature. Recently, titanium dioxide chromatography was introduced in proteomics as a highly specific method for enriching phosphorylated peptides - a method, which has been widely adapted by the field...... matrices for further characterization is affinity chromatography, which relies on the specific interaction between an analyte in solution and a solid adsorbent. Titanium dioxide-based affinity chromatography has proven to be a versatile tool in enrichment of various compounds such as phosphorylated....... The development of TiO(2)-based chromatographic strategies for separation of various biomolecules from its introduction for small molecules more than 20years ago until recent proteomics applications today will be reviewed here....

  13. Application of Fourier transform infrared spectroscopy to biomolecular profiling of cultured fibroblast cells from Gaucher disease patients: A preliminary investigation.

    Science.gov (United States)

    Igci, Nasit; Sharafi, Parisa; Demiralp, Duygu Ozel; Demiralp, Cemil Ozerk; Yuce, Aysel; Emre, Serap Dokmeci

    2017-10-01

    Gaucher disease (GD) is defined as an autosomal recessive disorder resulting from the deficiency of glucocerebrosidase (E.C. 3.2.1.45). Glucocerebrosidase is responsible for the degradation of glucosylceramide into ceramide and glucose. The deficiency of this enzyme results in the accumulation of undegraded glucosylceramide, almost exclusively in macrophages. With Fourier transform infrared (FTIR) spectroscopy, the complete molecular diversity of the samples can be studied comparatively and the amount of the particular materials can be determined. Also, the secondary structure ratios of proteins can be determined by analysing the amide peaks. The primary aim of this study is to introduce FTIR-ATR spectroscopy technique to GD research for the first time in the literature and to assess its potential as a new molecular method. Primary fibroblast cell cultures obtained from biopsy samples were used, since this material is widely used for the diagnosis of GD. Intact cells were placed onto a FTIR-ATR crystal and dried by purging nitrogen gas. Spectra were recorded in the mid-infrared region between 4500-850 cm-1 wavenumbers. Each peak in the spectra was assigned to as organic biomolecules according to their chemical bond information. A quantitative analysis was performed using peak areas and we also used a hierarchical cluster analysis as a multivariate spectral analysis. We obtained FTIR spectra of fibroblast samples and assigned the biomolecule origins of the peaks. We observed individual heterogeneity in FTIR spectra of GD fibroblast samples, confirming the well-known phenotypic heterogeneity in GD at the molecular level. Significant alterations in protein, lipid and carbohydrate levels related to the enzyme replacement therapy were also observed, which is also supported by cluster analysis. Our results showed that the application of FTIR spectroscopy to GD research deserves more attention and detailed studies with an increased sample size in order to evaluate its

  14. Zeta-potential data reliability of gold nanoparticle biomolecular conjugates and its application in sensitive quantification of surface absorbed protein.

    Science.gov (United States)

    Wang, Wenjie; Ding, Xiaofan; Xu, Qing; Wang, Jing; Wang, Lei; Lou, Xinhui

    2016-12-01

    Zeta potentials (ZP) of gold nanoparticle bioconjugates (AuNP-bios) provide important information on surface charge that is critical for many applications including drug delivery, biosensing, and cell imaging. The ZP measurements (ZPMs) are conducted under an alternative electrical field at a high frequency under laser irradiation, which may strongly affect the status of surface coating of AuNP-bios and generate unreliable data. In this study, we systemically evaluated the ZP data reliability (ZPDR) of citrate-, thiolated single stranded DNA-, and protein-coated AuNPs mainly according to the consistence of ZPs in the repeated ZPMs and the changes of the hydrodynamic size before and after the ZPMs. We found that the ZPDR was highly dependent on both buffer conditions and surface modifications. Overall, the higher ionic strength of the buffer and the lower affinity of surface bounders were related with the worse ZPDR. The ZPDR of citrate-coated AuNP was good in water, but bad in 10mM phosphate buffer (PB), showing substantially decrease of the absolute ZP values after each measurement, probably due to the electrical field facilitated adsorption of negatively charged phosphate ions on AuNPs. The significant desorption of DNAs from AuNP was observed in the PB containing medium concentration of NaCl, but not in PB. The excellent ZPDR of bovine serum albumin (BSA)-coated AuNP was observed at high salt concentrations and low surface coverage, enabling ZPM as an ultra-sensitive tool for protein quantification on the surface of AuNPs with a single molecule resolution. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. 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.

  16. 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.

  17. Improvements to the APBS biomolecular solvation software suite.

    Science.gov (United States)

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

    2018-01-01

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

  18. Smartphones for cell and biomolecular detection.

    Science.gov (United States)

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

    2014-11-01

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

  19. 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).

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

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  1. 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

  2. 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.

  3. 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...

  4. 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.)

  5. 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 ).

  6. 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 ).

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    National Research Council Canada - National Science Library

    Frazier, John; Chusak, Yaroslav; Foy, Brent

    2008-01-01

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

  12. 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.

  13. Application of radionuclide ventriculography to cardiac screening

    International Nuclear Information System (INIS)

    Lindsay, J. Jr.; Milner, M.R.; Chandeysson, P.L.; Rodman, D.J.; Okin, P.M.; Goldstein, S.A.

    1989-01-01

    Screening asymptomatic individuals for latent coronary disease often requires sequential testing because exercise electrocardiography typically produces more false positive than true positive results in a population with a low prevalence of coronary disease. Cardiac scintigraphy is a technique that may be employed as a confirmatory test in lieu of coronary arteriography to further evaluate the significance of a positive exercise electrocardiogram. Radionuclide ventriculography was employed in 98 asymptomatic individuals who were considered to be at moderate risk of heart disease after risk factor analysis and exercise electrocardiography. Seventeen (17%) patients had an abnormal study and underwent cardiac catheterization. Seven had coronary artery disease, two had cardiomyopathy, and eight were normal. Eighty-one (83%) patients had a normal study. Because the sensitivity of radionuclide ventriculography is 63-80%, it was postulated that 2 to 5 individuals with disease were missed. Thus, from a population with an 11-14% prevalence of disease, two subsets were identified. A large subset in which a prevalence of 2-6% could be estimated was separated from a much smaller one in which a prevalence of approximately 50% was demonstrated

  14. 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…

  15. 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.

  16. 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).

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Role of biomolecular logic systems in biosensors and bioactuators

    Science.gov (United States)

    Mailloux, Shay; Katz, Evgeny

    2014-09-01

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

  3. 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

  4. A survey of the 2001 to 2005 quartz crystal microbalance biosensor literature: applications of acoustic physics to the analysis of biomolecular interactions.

    Science.gov (United States)

    Cooper, Matthew A; Singleton, Victoria T

    2007-01-01

    The widespread exploitation of biosensors in the analysis of molecular recognition has its origins in the mid-1990s following the release of commercial systems based on surface plasmon resonance (SPR). More recently, platforms based on piezoelectric acoustic sensors (principally 'bulk acoustic wave' (BAW), 'thickness shear mode' (TSM) sensors or 'quartz crystal microbalances' (QCM)), have been released that are driving the publication of a large number of papers analysing binding specificities, affinities, kinetics and conformational changes associated with a molecular recognition event. This article highlights salient theoretical and practical aspects of the technologies that underpin acoustic analysis, then reviews exemplary papers in key application areas involving small molecular weight ligands, carbohydrates, proteins, nucleic acids, viruses, bacteria, cells and lipidic and polymeric interfaces. Key differentiators between optical and acoustic sensing modalities are also reviewed. Copyright (c) 2007 John Wiley & Sons, Ltd.

  5. 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.

  6. Biomolecular ions in superfluid helium nanodroplets

    International Nuclear Information System (INIS)

    Gonzalez Florez, Ana Isabel

    2016-01-01

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

  7. Biomolecular ions in superfluid helium nanodroplets

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez Florez, Ana Isabel

    2016-07-01

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

  8. 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.

  9. 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).

  10. 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…

  11. 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)

  12. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-10-24

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

  14. Marked Object Recognition Multitouch Screen Printed Touchpad for Interactive Applications.

    Science.gov (United States)

    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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. A statistical nanomechanism of biomolecular patterning actuated by surface potential

    Science.gov (United States)

    Lin, Chih-Ting; Lin, Chih-Hao

    2011-02-01

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

  4. 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.

  5. 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. PMID:26865904

  6. 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.

  7. Positrons in biomolecular systems. II

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  8. 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

  9. Biomolecular Assembly of Gold Nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Micheel, Christine Marya [Univ. of California, Berkeley, CA (United States)

    2005-05-20

    Over the past ten years, methods have been developed to construct discrete nanostructures using nanocrystals and biomolecules. While these frequently consist of gold nanocrystals and DNA, semiconductor nanocrystals as well as antibodies and enzymes have also been used. One example of discrete nanostructures is dimers of gold nanocrystals linked together with complementary DNA. This type of nanostructure is also known as a nanocrystal molecule. Discrete nanostructures of this kind have a number of potential applications, from highly parallel self-assembly of electronics components and rapid read-out of DNA computations to biological imaging and a variety of bioassays. My research focused in three main areas. The first area, the refinement of electrophoresis as a purification and characterization method, included application of agarose gel electrophoresis to the purification of discrete gold nanocrystal/DNA conjugates and nanocrystal molecules, as well as development of a more detailed understanding of the hydrodynamic behavior of these materials in gels. The second area, the development of methods for quantitative analysis of transmission electron microscope data, used computer programs written to find pair correlations as well as higher order correlations. With these programs, it is possible to reliably locate and measure nanocrystal molecules in TEM images. The final area of research explored the use of DNA ligase in the formation of nanocrystal molecules. Synthesis of dimers of gold particles linked with a single strand of DNA possible through the use of DNA ligase opens the possibility for amplification of nanostructures in a manner similar to polymerase chain reaction. These three areas are discussed in the context of the work in the Alivisatos group, as well as the field as a whole.

  10. Biomolecular strategies for cell surface engineering

    Science.gov (United States)

    Wilson, John Tanner

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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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...

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Electromagnetic radiation screening of microcircuits for long life applications

    Science.gov (United States)

    Brammer, W. G.; Erickson, J. J.; Levy, M. E.

    1974-01-01

    The utility of X-rays as a stimulus for screening high reliability semiconductor microcircuits was studied. The theory of the interaction of X-rays with semiconductor materials and devices was considered. Experimental measurements of photovoltages, photocurrents, and effects on specified parameters were made on discrete devices and on microcircuits. The test specimens included discrete devices with certain types of identified flaws and symptoms of flaws, and microcircuits exhibiting deviant electrical behavior. With a necessarily limited sample of test specimens, no useful correlation could be found between the X-ray-induced electrical response and the known or suspected presence of flaws.

  2. Computational Screening of Materials for Water Splitting Applications

    DEFF Research Database (Denmark)

    Castelli, Ivano Eligio

    Design new materials for energy production in a photoelectrochemical cell, where water is split into hydrogen and oxygen by solar light, is one possible solution to the problem of increasing energy demand and storage. A screening procedure based on ab-initio density functional theory calculations...... Project database, which is based on the experimental ICSD database, and the bandgaps were calculated with focus on finding materials with potential as light harvesters. 24 materials have been proposed for the one-photon water splitting and 23 for the two-photon mechanism. Another method to obtain energy...... from Sun is using a photovoltaic cell that converts solar light into electricity. The absorption spectra of 70 experimentally known compounds, that are expected to be useful for light-to-electricity generation, have been calculated. 17 materials have been predicted to be promising for a single...

  3. [Psychological distress in applicants for genetic screening for colorectal cancer].

    Science.gov (United States)

    Fantini, C; Pedinielli, J-L; Manouvrier, S

    2007-01-01

    Introduction. The development of a DNA based diagnostic test has allowed for the genetic screening of many hereditary diseases. In addition to the identification of the deleterious gene, this screening process has led to the recognition of developing illnesses at high risk. In recent years, a number of genes predisposing to an inherited cancer syndrome have been identified. Our purpose in this study was to determine whether subjects at risk who test for inherited colorectal cancer, are likely to develop a higher level of psychological distress than the norm, taking into consideration the particular history of this familial disease. The demographic and psychosocial aspects of our population was described using: 1) the State Trait Anxiety Inventory (STAI), 2) the Center for Epidemiologic Studies Depression (CES-D), 3) a perceived risk for the gene carrier, 4) subjective perception of personal vulnerability and 5) the role of the medical status (affected or not), which places the subject in either predisposition or predictive testing. Results show that our population had a higher predisposition for depressive disorders (chi2=9,3. p=0.002) and a significantly higher state of anxiety (chi2=9,3. p=0.002), prior to genetic counselling, compared with other populations. We found no evidence in the medical status, nor the perceived risk. However, the assessment of one's own personal vulnerability is related to psychological distress. These results highlight the particular vulnerability of subjects undergoing genetic testing as well as showing the pertinence of proposing psychological help throughout the process of these new specific diagnoses.

  4. PATHOS: a brief screening application for assessing sexual addiction.

    Science.gov (United States)

    Carnes, Patrick J; Green, Bradley A; Merlo, Lisa J; Polles, Alexis; Carnes, Stefanie; Gold, Mark S

    2012-03-01

    Sexual addiction is estimated to afflict up to 3% to 6% of the population. However, many clinicians lack clear criteria for detecting potential cases. The present studies were conducted to assess the effectiveness of a brief sexual addiction screening instrument (ie, PATHOS Questionnaire) to correctly classify patients being treated for sex addiction and healthy volunteers. In study 1, a 6-item questionnaire, which utilizes the mnemonic "PATHOS," was examined in regard to sensitivity and specificity using a sample combining patients being treated for sex addiction and healthy volunteers (970 men/80.2% patients; 938 women/63.8% patients). In study 2, a cross-validation sample of 672 men (93% patients) and 241 women (35.3% patients) completed the PATHOS screener. Results of receiver operating characteristics analyses in study 1 demonstrated that the PATHOS captured 92.6% of the area under the curve and achieved 88.3% sensitivity and 81.6% specificity for classifying the male sample (n = 963) as patients and healthy subjects using a cutoff score of 3. Similarly, the PATHOS captured 90.2% of the area under the curve and, with a cutoff of 3, achieved 80.9% sensitivity and 87.2% specificity for the female sample (n = 808). In study 2, results of receiver operating characteristics analyses indicated that the PATHOS captured 85.1% of the area under the curve, with sensitivity of 70.7% and specificity of 86.9% for men (cutoff of 3). For women, the PATHOS captured 80.9% of the area under the curve and achieved 69.7% sensitivity and 85.1% specificity with the cutoff of 3. These studies provide support for the use of the PATHOS as a screening instrument to detect potential sexual addiction cases in clinical settings.

  5. 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

  6. Application of corrosion screening tools for riser inspection

    International Nuclear Information System (INIS)

    Zamir Mohamed Daud; Vijayan, S.

    2003-01-01

    As offshore facilities approach the end of their design life, owners would like to assess the condition and integrity of plant and equipment. Detailed inspection, including non-destructive testing (NDT), are implemented and results are utilised for predictive maintenance and estimating useful remaining life. Except for risk based inspection, the extent of surface coverage required would be more compared to inspection of pre-determined spots. Risers, for example, usually have several layers of coating that prevent use of conventional techniques for inspection of corrosion. Complete coverage requires access (including removal coatings and insulation). Inspection utilising the conventional NDT tools can be very slow and expensive. However, recent advances have forwarded the use of specialised NDT techniques that were developed for inspection of corrosion under insulation (CUI). This paper details two screening inspection tools, LIXI Profiler and RTD-INCOTEST that have been applied to inspection of risers. LIXI Profiler is based on attenuation of penetrating radiation by materials, and RTD-INCOTEST is based on decay of pulsed eddy current in materials. (Author)

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Biomolecular detection using a metal semiconductor field effect transistor

    Science.gov (United States)

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

    2010-04-01

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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. [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.

  7. [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.

  8. Combining vibrational biomolecular spectroscopy with chemometric techniques for the study of response and sensitivity of molecular structures/functional groups mainly related to lipid biopolymer to various processing applications.

    Science.gov (United States)

    Yu, Gloria Qingyu; Yu, Peiqiang

    2015-09-01

    The objectives of this project were to (1) combine vibrational spectroscopy with chemometric multivariate techniques to determine the effect of processing applications on molecular structural changes of lipid biopolymer that mainly related to functional groups in green- and yellow-type Crop Development Centre (CDC) pea varieties [CDC strike (green-type) vs. CDC meadow (yellow-type)] that occurred during various processing applications; (2) relatively quantify the effect of processing applications on the antisymmetric CH3 ("CH3as") and CH2 ("CH2as") (ca. 2960 and 2923 cm(-1), respectively), symmetric CH3 ("CH3s") and CH2 ("CH2s") (ca. 2873 and 2954 cm(-1), respectively) functional groups and carbonyl C=O ester (ca. 1745 cm(-1)) spectral intensities as well as their ratios of antisymmetric CH3 to antisymmetric CH2 (ratio of CH3as to CH2as), ratios of symmetric CH3 to symmetric CH2 (ratio of CH3s to CH2s), and ratios of carbonyl C=O ester peak area to total CH peak area (ratio of C=O ester to CH); and (3) illustrate non-invasive techniques to detect the sensitivity of individual molecular functional group to the various processing applications in the recently developed different types of pea varieties. The hypothesis of this research was that processing applications modified the molecular structure profiles in the processed products as opposed to original unprocessed pea seeds. The results showed that the different processing methods had different impacts on lipid molecular functional groups. Different lipid functional groups had different sensitivity to various heat processing applications. These changes were detected by advanced molecular spectroscopy with chemometric techniques which may be highly related to lipid utilization and availability. The multivariate molecular spectral analyses, cluster analysis, and principal component analysis of original spectra (without spectral parameterization) are unable to fully distinguish the structural differences in the

  9. 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)

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  19. Development of Microdevices for Biomolecular Detection

    National Research Council Canada - National Science Library

    Manalis, Scott R

    2008-01-01

    .... In particular, glass encapsulated field-effect sensors that are chemically robust and batch-fabricated by a conventional 6" wafer process were developed and demonstrated for the following applications...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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)

  11. Exploring the Impact of Applicants' Gender and Religion on Principals' Screening Decisions for Assistant Principal Applicants

    Science.gov (United States)

    Bon, Susan C.

    2009-01-01

    In this experimental study, a national random sample of high school principals (stratified by gender) were asked to evaluate hypothetical applicants whose resumes varied by religion (Jewish, Catholic, nondenominational) and gender (male, female) for employment as assistant principals. Results reveal that male principals rate all applicants higher…

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-12-31

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

  13. Molecular-dynamics simulations of polymeric surfaces for biomolecular applications

    NARCIS (Netherlands)

    Muntean, S.A.

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  15. 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

  16. Biomolecular Characterization of Putative Antidiabetic Herbal Extracts

    Science.gov (United States)

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

    2016-01-01

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

  17. 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...

  18. 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.

  19. 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.

  20. 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)

  1. 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.

  2. [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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    Science.gov (United States)

    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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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)

  18. 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.

  19. 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)

  20. 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.

  1. 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

  2. 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...

  3. 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.

  4. 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.

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

    Science.gov (United States)

    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.

  6. 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 ...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    Science.gov (United States)

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

    2010-09-20

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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Mary E Prendergast

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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. Evolution of biomolecular loadings along a major river system

    Science.gov (United States)

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

    2018-02-01

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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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.

  11. 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.

  12. 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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Michael Hausmann

    2017-09-01

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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. 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.

  19. Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Model Applications to Screen Environmental Hazards.

    Science.gov (United States)

    This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. A...

  20. Application of EU guidelines for the validation of screening methods for veterinary drugs

    NARCIS (Netherlands)

    Stolker, A.A.M.

    2012-01-01

    Commission Decision (CD) 2002/657/EC describes detailed rules for method validation within the framework of residue monitoring programmes. The approach described in this CD is based on criteria. For (qualitative) screening methods, the most important criteria is that the CCß has to be below any

  1. Defining the taxonomic domain of applicability for mammalian-based high-throughput screening assays

    Science.gov (United States)

    Cell-based high throughput screening (HTS) technologies are becoming mainstream in chemical safety evaluations. The US Environmental Protection Agency (EPA) Toxicity Forecaster (ToxCastTM) and the multi-agency Tox21 Programs have been at the forefront in advancing this science, m...

  2. The CALUX bioassay: current status of its application to screening food and feed

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.; Goeyens, L.; Carbonnelle, S.; Loco, van J.; Beernaert, H.; Baeyens, W.; Traag, W.A.; Bovee, T.F.H.; Jacobs, G.; Schoeters, G.

    2006-01-01

    The CALUX bioassay is at present the best screening method for dioxins and dioxin-like (dl) polychlorinated biphenyls (PCBs) in food and feed, and the only assay used in routine monitoring and during larger incidents. Furthermore, the use of bioassays in addition to chemical reference methods allows

  3. Video Tape Application to Higher Education: Pre-Employment Screening. Final Report.

    Science.gov (United States)

    Millet, June E.; Smith, Lawrence H.

    Significant needs and additional pressures have been imposed on those persons involved in faculty selection activities on college campuses today. The combination of greater numbers of highly qualified candidates and restricted interview budgets suggests the need for more efficient and less costly methods of employment screening. In addition,…

  4. 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.

  5. The 4P's Plus screen for substance use in pregnancy: clinical application and outcomes.

    Science.gov (United States)

    Chasnoff, Ira J; McGourty, Richard F; Bailey, Gregory W; Hutchins, Ellen; Lightfoot, Saundra O; Pawson, Leslie Lynn; Fahey, Cynthia; May, Barbara; Brodie, Paula; McCulley, Larry; Campbell, Jan

    2005-06-01

    Determine the prevalence of substance use among pregnant women in five diverse communities utilizing the 4P's Plus screen for alcohol, tobacco, and other drug use. Pregnant women enrolled in prenatal care clinics in five communities were screened for substance use with the 4P's Plus. Those women with a positive screen underwent an assessment for substance use through a follow-up structured clinical interview conducted at the same prenatal visit. Among 7818 women in five communities, 2555 (32.7%) had a positive screen for substance use in pregnancy. Four of the communities conducted a follow-up assessment on all women with a positive screen (n = 1548). Among these women, 717 (15% of the total population) had continued use after learning of the pregnancy. Overall, 21% of the pregnant women used alcohol prior to recognition of the pregnancy, and 11% continued use after knowledge of the pregnancy. Among the 512 women who continued to use alcohol, 2% were drinking daily, 7% were drinking 3 to 6 days per week, 27% were drinking 1 to 2 days per week, and 63% were drinking less than 1 day per week. The rates of marijuana use and other illicit drug use among the women were 7 and 2%, respectively, prior to knowledge of pregnancy and dropped to 3 and 1% after learning of the pregnancy. The 4P's Plus identifies not only those pregnant women whose drinking or drug use is at a high enough level to impair daily functioning, but provides an opportunity for early intervention for the much larger group of women whose pregnancies are at risk from relatively small amounts of substance use.

  6. 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.

  7. 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.

  8. Application of NMR Screening Methods with 19F Detection to Fluorinated Compounds Bound to Proteins

    Directory of Open Access Journals (Sweden)

    Kazuo Furihata

    2017-12-01

    Full Text Available The combinational use of one-dimensional (1D NMR-based screening techniques with 1H and 19F detections were applied to a human serum albumin–diflunisal complex. Since most NMR screening methods observe 1H spectra, the overlapped 1H signals were unavailable in the binding epitope mapping. However, the NMR experiments with 19F detection can be used as an effective complementary method. For the purpose of identifying the 1H and 19F binding epitopes of diflunisal, this paper carries out a combinatorial analysis using 1H{1H} and 19F{1H} saturation transfer difference experiments. The differences of the 1H-inversion recovery rates with and without target irradiation are also analyzed for a comprehensive interpretation of binding epitope mapping.

  9. Accurate collision integrals for the attractive static screened Coulomb potential with application to electrical conductivity

    International Nuclear Information System (INIS)

    Macdonald, J.

    1991-01-01

    The results of accurate calculations of collision integrals for the attractive static screened Coulomb potential are presented. To obtain high accuracy with minimal computational cost, the integrals are evaluated by a quadrature method based on the Whittaker cardinal function. The collision integrals for the attractive potential are needed for calculation of the electrical conductivity of a dense fully or partially ionized plasma, and the results presented here are appropriate for the conditions in the nondegenerate envelopes of white dwarf stars. 25 refs

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  11. 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

  12. 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.

  13. ALTERNATIVAS BIOMOLECULARES EN EL TRATAMIENTO DE LA OBESIDAD

    Directory of Open Access Journals (Sweden)

    Fernando Lizcano

    2010-09-01

    Full Text Available

    Resumen

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

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

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

    BIOMOLECULAR OPTIONS IN TREATING OBESITY

    Abstract

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

  14. 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

  15. High voltage series resonant inverter ion engine screen supply. [SCR series resonant inverter for space applications

    Science.gov (United States)

    Biess, J. J.; Inouye, L. Y.; Shank, J. H.

    1974-01-01

    A high-voltage, high-power LC series resonant inverter using SCRs has been developed for an Ion Engine Power Processor. The inverter operates within 200-400Vdc with a maximum output power of 2.5kW. The inverter control logic, the screen supply electrical and mechanical characteristics, the efficiency and losses in power components, regulation on the dual feedback principle, the SCR waveforms and the component weight are analyzed. Efficiency of 90.5% and weight density of 4.1kg/kW are obtained.

  16. 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

  17. Isolation, screening and identification of novel isolates of Actinomycetes from India for antimicrobial applications

    Directory of Open Access Journals (Sweden)

    Vineeta Singh

    2016-12-01

    Full Text Available The search for novel bioactive compounds from the natural environment has been rapidly increased with the increase in multi-drug resistant (MDR pathogens. In the present study, the antimicrobial potential of novel actinomycetes has been evaluated by initial screening of six soil samples. Primary and secondary screening was performed against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Candida albicans, Candida tropicalis, Trichophyton rubrum, and other MDR bacterial and fungal test strains, and at the end thirteen active isolates were selected for further study. Microbial strains were identified on the basis of growth conditions and other biochemical characters. Five most active microbial strains were identified using 16S rRNA sequence homology and designated as Streptomyces xanthophaeus MTCC 11938, Streptomyces variabilis MTCC 12266, Streptomyces xanthochromogenes MTCC 11937, Streptomyces levis EU 124569 and Streptomyces sp. NCIM 5500. Four antibacterial and three antifungal compounds isolated from the above five isolates were purified and partially characterized using UV absorption and IR spectra. Two antibacterial metabolites, belong to chromone and peptide antibiotic, respectively. The antifungal compounds were found to be of non-polyene nature. In conclusion, we study the isolation of novel bacterial strains of actinomycetes for producing novel compounds having antibacterial and antifungal activities from the unexplored agro-ecological niches of India. Also, this study paves the way for further characterization of these isolates of Streptomyces sp. for their optimum utilization for antimicrobial purposes.

  18. Development of thermal stress screening method. Application of green function method

    International Nuclear Information System (INIS)

    Furuhashi, Ichiro; Shibamoto, Hiroshi; Kasahara, Naoto

    2004-01-01

    This work was achieved for the development of the screening method of thermal transient stresses in FBR components. We proposed an approximation method for evaluations of thermal stress under variable heat transfer coefficients (non-linear problems) using the Green functions of thermal stresses with constant heat transfer coefficients (linear problems). Detailed thermal stress analyses provided Green functions for a skirt structure and a tube-sheet of Intermediate Heat Exchanger. The upper bound Green functions were obtained by the analyses using those upper bound heat transfer coefficients. The medium and the lower bound Green functions were got by the analyses of those under medium and the lower bound heat transfer coefficients. Conventional evaluations utilized the upper bound Green functions. On the other hand, we proposed a new evaluation method by using the upper bound, medium and the lower bound Green functions. The comparison of above results gave the results as follows. The conventional evaluations were conservative and appropriate for the cases under one fluid thermal transient structure such as the skirt. The conventional evaluations were generally conservative for the complicated structures under two or more fluids thermal transients such as the tube-sheet. But the danger locations could exists for the complicated structures under two or more fluids transients, namely the conventional evaluations were non-conservative. The proposed evaluations gave good estimations for these complicated structures. Though above results, we have made the basic documents of the screening method of thermal transient stresses using the conventional method and the new method. (author)

  19. In vitro application of integrated selection index for screening drought tolerant genotypes in common wheat

    Directory of Open Access Journals (Sweden)

    Ezatollah FARSHADFAR

    2016-10-01

    Full Text Available This experiment was conducted on 20 wheat genotypes during 2010-2011 growing season at the Razi University, Kermanshah, Iran. A completely randomized design with six replications was used for callus induction and a 20 × 2 factorial experiment with three replications was used for response of genotypes to in vitro drought stress. ANOVA exhibited highly significant differences among the genotypes for callus growth rate, relative fresh mass growth, relative growth rate, callus water content, percent of callus chlorosis and proline content under stress condition (15 % PEG. PCA showed that the integrated selection index was correlated with callus growth index, relative fresh mass growth, relative growth rate and proline content indicating that these screening techniques can be useful for selecting drought tolerant genotypes. Screening drought tolerant genotypes and in vitro indicators of drought tolerance using mean rank, standard deviation of ranks and biplot analysis, discriminated genotypes 2, 18 and 10 as the most drought tolerant. Therefore they are recommended to be used as parents for genetic analysis, gene mapping and improvement of drought tolerance.

  20. 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…

  1. SWAT Check: A Screening Tool to Assist Users in the Identification of Potential Model Application Problems.

    Science.gov (United States)

    White, Michael J; Harmel, R Daren; Arnold, Jeff G; Williams, Jimmy R

    2014-01-01

    The Soil and Water Assessment Tool (SWAT) is a basin-scale hydrologic model developed by the United States Department of Agriculture Agricultural Research Service. SWAT's broad applicability, user-friendly model interfaces, and automatic calibration software have led to a rapid increase in the number of new users. These advancements also allow less experienced users to conduct SWAT modeling applications. In particular, the use of automated calibration software may produce simulated values that appear appropriate because they adequately mimic measured data used in calibration and validation. Autocalibrated model applications (and often those of unexperienced modelers) may contain input data errors and inappropriate parameter adjustments not readily identified by users or the autocalibration software. The objective of this research was to develop a program to assist users in the identification of potential model application problems. The resulting "SWAT Check" is a stand-alone Microsoft Windows program that (i) reads selected SWAT output and alerts users of values outside the typical range; (ii) creates process-based figures for visualization of the appropriateness of output values, including important outputs that are commonly ignored; and (iii) detects and alerts users of common model application errors. By alerting users to potential model application problems, this software should assist the SWAT community in developing more reliable modeling applications. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  2. 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 ...

  3. Immobilization of Acetylcholinesterase on Screen-Printed Electrodes. Application to the Determination of Arsenic(III

    Directory of Open Access Journals (Sweden)

    M. Julia Arcos-Martínez

    2010-03-01

    Full Text Available Enzymatic amperometric procedures for measuring arsenic, based on the inhibitive action of this metal on acetylcholinesterase enzyme activity, have been developed. Screen-printed carbon electrodes (SPCEs were used with acetylcholinesterase covalently bonded directly to its surface. The amperometric response of acetylcholinesterase was affected by the presence of arsenic ions, which caused a decrease in the current intensity. The experimental optimum working conditions of pH, substrate concentration and potential applied, were established. Under these conditions, repeatability and reproducibility of biosensors were determined, reaching values below 4% in terms of relative standard deviation. The detection limit obtained for arsenic was 1.1 × 10−8 M for Ach/SPCE biosensor. Analysis of the possible effect of the presence of foreign ions in the solution was performed. The method was applied to determine levels of arsenic in spiked tap water samples.

  4. Screening of chlorpyrifos degrading bacteria CD7 and its combined application with PGPR JD37

    Directory of Open Access Journals (Sweden)

    Su Cuizhu

    2017-04-01

    Full Text Available We screened a chlorpyrifos degrading bacteria,Burkholderiasp. CD7.Joint with plant growth-promoting rhizobacteria(PGPR JD37 to produce a compositesoil amendment,which could restorethe pesticides polluted soil and promote plant growth.Results showed that CD7 and JD37 (at the volume ratio of 1:1 can promote the growth of plants,and within 25 days degrade about 66.43% chlorpyrifos in the soil.Further research found that under the same conditions of carrier dosage,vermicompost can adsorbed more bacteria than talcum powder;after a month preservation at room temperature,the number of living bacterium still maintained about 4.81×107 CFU/g.Carrier and soil,at the mass ratio of 1:1,could optimally promote plant growth,improve soil enzyme activities and increase the number of microorganisms in soil.

  5. Germanium doping of GaN by metalorganic chemical vapor deposition for polarization screening applications

    KAUST Repository

    Young, N.G.; Farrell, R.M.; Iza, M.; Nakamura, S.; DenBaars, S.P.; Weisbuch, C.; Speck, J.S.

    2016-01-01

    We demonstrate n-type doping of GaN with Ge by MOCVD at high concentrations that are necessary to fully screen the polarization fields in c-plane InGaN/GaN quantum wells. Hall measurements show linear Ge incorporation with dopant flow rate and carrier concentrations exceeding 1×10 cm. GaN:Ge layers exhibit excellent electron mobility, high conductivity, and contact resistivity comparable to the best unannealed contacts to Si-doped GaN. However, the surface morphology begins to degrade with Ge concentrations above 1×10 cm, resulting in severe step bunching and a network of plateaus and trenches, even in layers as thin as 10 nm.

  6. Germanium doping of GaN by metalorganic chemical vapor deposition for polarization screening applications

    KAUST Repository

    Young, N.G.

    2016-10-01

    We demonstrate n-type doping of GaN with Ge by MOCVD at high concentrations that are necessary to fully screen the polarization fields in c-plane InGaN/GaN quantum wells. Hall measurements show linear Ge incorporation with dopant flow rate and carrier concentrations exceeding 1×10 cm. GaN:Ge layers exhibit excellent electron mobility, high conductivity, and contact resistivity comparable to the best unannealed contacts to Si-doped GaN. However, the surface morphology begins to degrade with Ge concentrations above 1×10 cm, resulting in severe step bunching and a network of plateaus and trenches, even in layers as thin as 10 nm.

  7. Application of Short Screening Tools for Post-Traumatic Stress Disorder in the Korean Elderly Population

    Science.gov (United States)

    Jang, Yu Jin; Chung, Hae Gyung; Choi, Jin Hee; Kim, Tae Yong; So, Hyung Seok

    2016-01-01

    Objective Post-traumatic stress disorder (PTSD) is often missed or incorrectly diagnosed in primary care settings. Although brief screening instruments may be useful in detecting PTSD, an adequate validation study has not been conducted with older adults. This study aimed to evaluate the reliability and validity of the Korean version of the primary care PTSD screen (PC-PTSD) and single-item PTSD screener (SIPS) in elderly veterans. Methods The PC-PTSD and SIPS assessments were translated into Korean, with a back-translation to the original language to verify accuracy. Vietnamese war veterans [separated into a PTSD group (n=41) and a non-PTSD group (n=99)] participated in several psychometric assessments, including the Korean versions of the PC-PTSD (PC-PTSD-K), SIPS (SIPS-K), a structured clinical interview from the Diagnostic and Statistical Manual of Mental Disorders-IV(SCID), and PTSD checklist(PCL). Results The PC-PTSD-K showed high internal consistency (Cronbach α=0.76), and the test-retest reliability of the PC-PTSD-K and SIPS-K were also high (r=0.97 and r=0.91, respectively). A total score of 3 from the PC-PTSD-K yielded the highest diagnostic efficiency, with sensitivity and specificity values of 0.90 and 0.86, respectively. The 'bothered a lot' response level from the SIPS-K showed the highest diagnostic efficiency, with sensitivity and specificity values of 0.85 and 0.89, respectively. Conclusion Our findings suggest that both PC-PTSD-K and SIPS-K have good psychometric properties with high validity and reliability for detecting PTSD symptoms in elderly Korean veterans. However, further research will be necessary to increase our understanding of PTSD characteristics in diverse groups with different types of trauma. PMID:27482241

  8. An indole-deficient Escherichia coli strain improves screening of cytochromes P450 for biotechnological applications.

    Science.gov (United States)

    Brixius-Anderko, Simone; Hannemann, Frank; Ringle, Michael; Khatri, Yogan; Bernhardt, Rita

    2017-05-01

    Escherichia coli has developed into an attractive organism for heterologous cytochrome P450 production, but, in some cases, was restricted as a host in view of a screening of orphan cytochromes P450 or mutant libraries in the context of molecular evolution due to the formation of the cytochrome P450 inhibitor indole by the enzyme tryptophanase (TnaA). To overcome this effect, we disrupted the tnaA gene locus of E. coli C43(DE3) and evaluated the new strain for whole-cell substrate conversions with three indole-sensitive cytochromes P450, myxobacterial CYP264A1, and CYP109D1 as well as bovine steroidogenic CYP21A2. For purified CYP264A1 and CYP21A2, the half maximal inhibitory indole concentration was determined to be 140 and 500 μM, which is within the physiological concentration range occurring during cultivation of E. coli in complex medium. Biotransformations with C43(DE3)_∆tnaA achieved a 30% higher product formation in the case of CYP21A2 and an even fourfold increase with CYP264A1 compared with C43(DE3) cells. In whole-cell conversion based on CYP109D1, which converts indole to indigo, we could successfully avoid this reaction. Results in microplate format indicate that our newly designed strain is a suitable host for a fast and efficient screening of indole-influenced cytochromes P450 in complex medium. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  9. 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.

  10. 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.

  11. EXPLORING THE IMPACT OF APPLICANTS’ GENDER AND RELIGION ON PRINCIPALS’ SCREENING DECISIONS FOR ASSISTANT PRINCIPAL APPLICANTS

    Directory of Open Access Journals (Sweden)

    SUSAN C. BON

    2009-02-01

    Full Text Available In this experimental study, a national random sample of high school principals (stratified by gender were asked to evaluate hypothetical applicants whose resumes varied by religion (Jewish, Catholic, nondenominational and gender (male, female for employment as assistant principals. Results reveal that male principals rate all applicants higher than female principals and that the gender and religion of applicants failed to negatively or positively affect principals’ evaluations. These results suggest that discrimination based on an applicant’s gender and religion failed to be manifested during the pre-interview stage of the selection process. The paper concludes with a theoretical discussion of the distinction between explicit and implicit prejudice, and encourages future researchers to investigate the potential impact of prejudice on employment selection decisions and to consider whether schools should promote diversity in leadership positions.

  12. The structural bioinformatics library: modeling in biomolecular science and beyond.

    Science.gov (United States)

    Cazals, Frédéric; Dreyfus, Tom

    2017-04-01

    Software in structural bioinformatics has mainly been application driven. To favor practitioners seeking off-the-shelf applications, but also developers seeking advanced building blocks to develop novel applications, we undertook the design of the Structural Bioinformatics Library ( SBL , http://sbl.inria.fr ), a generic C ++/python cross-platform software library targeting complex problems in structural bioinformatics. Its tenet is based on a modular design offering a rich and versatile framework allowing the development of novel applications requiring well specified complex operations, without compromising robustness and performances. The SBL involves four software components (1-4 thereafter). For end-users, the SBL provides ready to use, state-of-the-art (1) applications to handle molecular models defined by unions of balls, to deal with molecular flexibility, to model macro-molecular assemblies. These applications can also be combined to tackle integrated analysis problems. For developers, the SBL provides a broad C ++ toolbox with modular design, involving core (2) algorithms , (3) biophysical models and (4) modules , the latter being especially suited to develop novel applications. The SBL comes with a thorough documentation consisting of user and reference manuals, and a bugzilla platform to handle community feedback. The SBL is available from http://sbl.inria.fr. Frederic.Cazals@inria.fr. 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

  13. 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.

  14. 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.

  15. Three dimensional de novo micro bone marrow and its versatile application in drug screening and regenerative medicine.

    Science.gov (United States)

    Li, Guanqun; Liu, Xujun; Du, Qian; Gao, Mei; An, Jing

    2015-08-01

    The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field. © 2015 by the Society for Experimental Biology and Medicine.

  16. Predictive Power of Machine Learning for Optimizing Solar Water Heater Performance: The Potential Application of High-Throughput Screening

    Directory of Open Access Journals (Sweden)

    Hao Li

    2017-01-01

    Full Text Available Predicting the performance of solar water heater (SWH is challenging due to the complexity of the system. Fortunately, knowledge-based machine learning can provide a fast and precise prediction method for SWH performance. With the predictive power of machine learning models, we can further solve a more challenging question: how to cost-effectively design a high-performance SWH? Here, we summarize our recent studies and propose a general framework of SWH design using a machine learning-based high-throughput screening (HTS method. Design of water-in-glass evacuated tube solar water heater (WGET-SWH is selected as a case study to show the potential application of machine learning-based HTS to the design and optimization of solar energy systems.

  17. Maryland Power Plant Siting Project: an application of the ORNL-Land Use Screening Procedure

    International Nuclear Information System (INIS)

    Dobson, J.E.

    1975-01-01

    Since 1974 the Resource Analysis Group in the Regional and Urban Studies Section of the Oak Ridge National Laboratory (ORNL) has been engaged in developing a procedure for regional and local siting analysis known as the ORNL Land Use Screening Procedure (LUSP). This document is the final report of the Maryland Power Plant Siting Project (MPPSP) in which the ORNL LUSP was used to identify candidate areas for power plant sites in northern Maryland. Numerous candidate areas are identified on the basis of four different siting objectives: the minimization of adverse ecologic impact, the minimization of adverse socioeconomic impact, the minimization of construction and operating costs, and a composite of all siting objectives. Siting criteria have been defined for each of these objectives through group processing techniques administered to four different groups of siting specialists. The siting priorities and opinions of each group have been expressed quantitatively and applied to a geographic information system containing 52 variables for each 91.8-acre cell in the northern eight counties of Maryland

  18. Malignant transformation in vitro: criteria, biological markers, and application in environmental screening of carcinogens

    International Nuclear Information System (INIS)

    Borek, C.

    1979-01-01

    Biological markers which distinguish malignantly transformed fibroblasts from their normal counterpart include pleomorphic morphology, lowered requirement for nutritional factors, loss of density inhibition of growth, complex topography as discernible by scanning electron microscopy, loss in surface proteins, incomplete glycosylation of membrane glycolylipids and glycoproteins, increased production of specific proteases, decreased organization of the cytoskeleton, and acquisition of neoantigens. Several of these markers are not consistently found in transformed epithelial cells and therefore cannot serve to distinguish unequivocally neoplastic epithelial cells from the normal counterparts. The only criteria associated with the transformed nature of both fibroblasts and epithelial cells are the ability of the cells to proliferate in semisolid medium and to induce tumors in appropriate hosts. In vitro systems represent a powerful tool for screening the mutagenic/oncogenic potential of physical, chemical, and environmental agents. Fibroblasts rather than epithelial cells are preferred for this purpose at the present time because of the clear-cut phenotypic differences between the normal and the transformed cells. These systems have been useful in establishing that malignant transformation can be induced by doses as low as 1 rad of X rays or 0.1 rad of neutrons, and that fractionation at low dose levelsleads to enhanced transformation. They have been useful in identifying a large number of hazardous chemicals and in evaluating the relationship between the mutagenic and carcinogenic potential of radiation and chemicals

  19. Maryland Power Plant Siting Project: an application of the ORNL-Land Use Screening Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Dobson, J.E.

    1975-01-01

    Since 1974 the Resource Analysis Group in the Regional and Urban Studies Section of the Oak Ridge National Laboratory (ORNL) has been engaged in developing a procedure for regional and local siting analysis known as the ORNL Land Use Screening Procedure (LUSP). This document is the final report of the Maryland Power Plant Siting Project (MPPSP) in which the ORNL LUSP was used to identify candidate areas for power plant sites in northern Maryland. Numerous candidate areas are identified on the basis of four different siting objectives: the minimization of adverse ecologic impact, the minimization of adverse socioeconomic impact, the minimization of construction and operating costs, and a composite of all siting objectives. Siting criteria have been defined for each of these objectives through group processing techniques administered to four different groups of siting specialists. The siting priorities and opinions of each group have been expressed quantitatively and applied to a geographic information system containing 52 variables for each 91.8-acre cell in the northern eight counties of Maryland.

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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.

  8. 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.

  9. Successful application of virtual screening and molecular dynamics simulations against antimalarial molecular targets

    Directory of Open Access Journals (Sweden)

    Renata Rachide Nunes

    Full Text Available The main challenge in the control of malaria has been the emergence of drug-resistant parasites. The presence of drug-resistant Plasmodium sp. has raised the need for new antimalarial drugs. Molecular modelling techniques have been used as tools to develop new drugs. In this study, we employed virtual screening of a pyrazol derivative (Tx001 against four malaria targets: plasmepsin-IV, plasmepsin-II, falcipain-II, and PfATP6. The receiver operating characteristic curves and area under the curve (AUC were established for each molecular target. The AUC values obtained for plasmepsin-IV, plasmepsin-II, and falcipain-II were 0.64, 0.92, and 0.94, respectively. All docking simulations were carried out using AutoDock Vina software. The ligand Tx001 exhibited a better interaction with PfATP6 than with the reference compound (-12.2 versus -6.8 Kcal/mol. The Tx001-PfATP6 complex was submitted to molecular dynamics simulations in vacuum implemented on an NAMD program. The ligand Tx001 docked at the same binding site as thapsigargin, which is a natural inhibitor of PfATP6. Compound TX001 was evaluated in vitro with a P. falciparum strain (W2 and a human cell line (WI-26VA4. Tx001 was discovered to be active against P. falciparum (IC50 = 8.2 µM and inactive against WI-26VA4 (IC50 > 200 µM. Further ligand optimisation cycles generated new prospects for docking and biological assays.

  10. Application of support vector machines to breast cancer screening using mammogram and clinical history data

    Science.gov (United States)

    Land, Walker H., Jr.; McKee, Dan; Velazquez, Roberto; Wong, Lut; Lo, Joseph Y.; Anderson, Francis R.

    2003-05-01

    The objectives of this paper are to discuss: (1) the development and testing of a new Evolutionary Programming (EP) method to optimally configure Support Vector Machine (SVM) parameters for facilitating the diagnosis of breast cancer; (2) evaluation of EP derived learning machines when the number of BI-RADS and clinical history discriminators are reduced from 16 to 7; (3) establishing system performance for several SVM kernels in addition to the EP/Adaptive Boosting (EP/AB) hybrid using the Digital Database for Screening Mammography, University of South Florida (DDSM USF) and Duke data sets; and (4) obtaining a preliminary evaluation of the measurement of SVM learning machine inter-institutional generalization capability using BI-RADS data. Measuring performance of the SVM designs and EP/AB hybrid against these objectives will provide quantative evidence that the software packages described can generalize to larger patient data sets from different institutions. Most iterative methods currently in use to optimize learning machine parameters are time consuming processes, which sometimes yield sub-optimal values resulting in performance degradation. SVMs are new machine intelligence paradigms, which use the Structural Risk Minimization (SRM) concept to develop learning machines. These learning machines can always be trained to provide global minima, given that the machine parameters are optimally computed. In addition, several system performance studies are described which include EP derived SVM performance as a function of: (a) population and generation size as well as a method for generating initial populations and (b) iteratively derived versus EP derived learning machine parameters. Finally, the authors describe a set of experiments providing preliminary evidence that both the EP/AB hybrid and SVM Computer Aided Diagnostic C++ software packages will work across a large population of patients, based on a data set of approximately 2,500 samples from five different

  11. River catchment responses to anthropogenic acidification in relationship with sewage effluent: An ecotoxicology screening application.

    Science.gov (United States)

    Oberholster, P J; Botha, A-M; Hill, L; Strydom, W F

    2017-12-01

    Rising environmental pressures on water resources and resource quality associated with urbanisation, industrialisation, mining and agriculture are a global concern. In the current study the upper Olifants River catchment as case study was used, to show that acid mine drainage (AMD) and acid precipitation were the two most important drivers of possible acidification during a four-year study period. Over the study period 59% of the precipitation sampled was classified as acidic with a pH value below 5.6. Traces of acidification in the river system using aquatic organisms at different trophic levels were only evident in areas of AMD point sources. Data gathered from the ecotoxicology screening tools, revealed that discharge of untreated and partially treated domestic sewage from municipal sewage treatment works and informal housing partially mitigate any traces of acidification by AMD and acid precipitation in the main stem of the upper Olifants River. The outcome of the study using phytoplankton and macroinvertebrates as indicator organisms revealed that the high loads of sewage effluent might have played a major role in the neutralization of acidic surface water conditions caused by AMD and acid precipitation. Although previous multi-stage and microcosm studies confirmed the decrease in acidity and metals concentrations by municipal wastewater, the current study is the first to provide supportive evidence of this co-attenuation on catchment scale. These findings are important for integrated water resource management on catchment level, especially in river systems with a complex mixture of pollutants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A Neuropsychological Approach of Developmental Dyscalculia and a Screening Test Via a Web Application

    Directory of Open Access Journals (Sweden)

    Nikolaos Christos Zygouris

    2017-11-01

    Full Text Available Traditional definitions of Developmental Dyscalculia state that a child must substantially underachieve on mathematical abilities tests relative to the level expected given age, education and intelligence. However, cognitive developmental neuropsychological studies nowadays suggest that not only core numerical but also cognitive skills of children with developmental dyscalculia present deficits. The main aim of the research protocol was to construct a battery of six tests that can be delivered by computer in order to screen children’s arithmetic and cognitive skills. The hypothesis of the study was that children that are already diagnosed by paper and pencil tests as dyscalculic will present lower scores and larger time latencies not only in arithmetical but also in executive function tasks. A total of 134 right handed children (74 male and 60 female, age range 8 – 12 years participated in this study. The students with disorders in mathematics (N= 67, 37 male and 30 female age range 8 – 12 years M= 10.15 SD=1.10 had a statement of dyscalculia after assessment at a Centre of Diagnosis, Assessment and Support, as it is required by Greek Law. A comparison group without any learning disabilities was individually matched with the dyscalculic group according to age, sex and grade (N=67, 37 male and 30 female, age range 8 – 12 years old, M=10.24 SD=1.12. Statistical analysis revealed that children with dyscalculia had statistically significant lower mean scores of correct answers and larger time latencies in all tasks compared to their average peers that participated in the comparison group.`

  13. Screening of various low-grade biomass materials for low temperature gasification: Method development and application

    DEFF Research Database (Denmark)

    Thomsen, Tobias Pape; Ravenni, Giulia; Holm, Jens Kai

    2015-01-01

    references. The technical assessment is supplemented by an evaluation of practical application and overall energy balance. Applying the developed method to 4 references and 18 unproven low-grade potential fuels, indicated that one of these unproven candidates was most likely unsuited for Pyroneer...... method and the subsequent use of the method to identify promising e but currently unproven, low-grade biomass resources for conversion in Pyroneer systems. The technical assessment is conducted by comparing the results from a series of physical-mechanical and thermochemical experiments to a set of proven...

  14. 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)

  15. 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.

  16. 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)

  17. Assessment of the application of an ecotoxicological procedure to screen illicit toxic discharges in domestic septic tank sludge.

    Science.gov (United States)

    López-Gastey, J; Choucri, A; Robidoux, P Y; Sunahara, G I

    2000-06-01

    An innovative screening procedure has been developed to detect illicit toxic discharges in domestic septic tank sludge hauled to the Montreal Urban Community waste-water treatment plant. This new means of control is based on an integrative approach, using bioassays and chemical analyses. Conservative criteria are applied to detect abnormal toxicity with great reliability while avoiding false positive results. The complementary data obtained from toxicity tests and chemical analyses support the use of this efficient and easy-to-apply procedure. This study assesses the control procedure in which 231 samples were analyzed over a 30-month period. Data clearly demonstrate the deterrent power of an efficient control procedure combined with a public awareness campaign among the carriers. In the first 15 months of application, between January 1996 and March 1997, approximately 30% of the 123 samples analyzed showed abnormal toxicity. Between April 1997 and June 1998, that is, after a public hearing presentation of this procedure, this proportion dropped significantly to approximately 9% based on 108 analyzed samples. The results of a 30-month application of this new control procedure show the superior efficiency of the ecotoxicological approach compared with the previously used chemical control procedure. To be able to apply it effectively and, if necessary, to apply the appropriate coercive measures, ecotoxicological criteria should be included in regulatory guidelines.

  18. 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.

  19. Environmental Application of Reporter-Genes Based Biosensors for Chemical Contamination Screening

    Directory of Open Access Journals (Sweden)

    Matejczyk Marzena

    2014-12-01

    Full Text Available The paper presents results of research concerning possibilities of applications of reporter-genes based microorganisms, including the selective presentation of defects and advantages of different new scientific achievements of methodical solutions in genetic system constructions of biosensing elements for environmental research. The most robust and popular genetic fusion and new trends in reporter genes technology – such as LacZ (β-galactosidase, xylE (catechol 2,3-dioxygenase, gfp (green fluorescent proteins and its mutated forms, lux (prokaryotic luciferase, luc (eukaryotic luciferase, phoA (alkaline phosphatase, gusA and gurA (β-glucuronidase, antibiotics and heavy metals resistance are described. Reporter-genes based biosensors with use of genetically modified bacteria and yeast successfully work for genotoxicity, bioavailability and oxidative stress assessment for detection and monitoring of toxic compounds in drinking water and different environmental samples, surface water, soil, sediments.

  20. Application of laser-induced autofluorescence spectra detection in human colorectal cancer screening

    Science.gov (United States)

    Fu, Sheng; Chia, Teck-Chee; Kwek, Leong Chuan; Diong, Cheong Hoong; Tang, Choong Leong; Choen, Francis S.; Krishnan, S. M.

    2003-10-01

    We investigated 48 normal patients and 25 diseased patients using our laser-induced autofluorescence spectra detection system during their regular colonoscopy. The colon and rectum mucosa autofluorescence were excited by 405 nm continue wavelength laser. We observed that cancer or diseased colorectal mucosa, their autofluorescence spectra are significantly different from normal area. The autofluorescence spectra intensity at about 500 nm was been used for our intensity ratio characteristics intensity for our diagnostic algorithm. The intensity ratios of RI-680/I-500 and RI-630/I-500 were performed to identify the detection area. From experimental result we concluded that both intensity ratios of RI-680/I-500 and RI-630/I-500 as guidelines can detect cancerous and polyps disease completely. Our investigation provided some useful insight for laser induced autofluorescence spectra as a diagnosis technique for clinical application.

  1. Relaxing the electrostatic screening effect by patterning vertically-aligned silicon nanowire arrays into bundles for field emission application

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Yung-Jr, E-mail: yungjrhung@gmail.com [Department of Electronic Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei 106, Taiwan, ROC (China); Department of Photonics, National Sun Yat-sen University, No. 70, Lienhai Rd., Kaohsiung 80424, Taiwan, ROC (China); Graduate Institute of Electro-Optical Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei 106, Taiwan, ROC (China); Lee, San-Liang [Department of Electronic Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei 106, Taiwan, ROC (China); Graduate Institute of Electro-Optical Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei 106, Taiwan, ROC (China); Beng, Looi Choon [Faculty of Engineering, Multimedia University, Jalan Multimedia, 63100 Cyberjaya, Selangor (Malaysia); Chang, Hsuan-Chen [Department of Electronic Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei 106, Taiwan, ROC (China); Graduate Institute of Electro-Optical Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei 106, Taiwan, ROC (China); Huang, Yung-Jui [Graduate Institute of Electro-Optical Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei 106, Taiwan, ROC (China); Lee, Kuei-Yi; Huang, Ying-Sheng [Department of Electronic Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei 106, Taiwan, ROC (China); Graduate Institute of Electro-Optical Engineering, National Taiwan University of Science and Technology, No. 43, Sec. 4, Keelung Rd., Taipei 106, Taiwan, ROC (China)

    2014-04-01

    Top-down fabrication strategies are proposed and demonstrated to realize arrays of vertically-aligned silicon nanowire bundles and bundle arrays of carbon nanotube–silicon nanowire (CNT–SiNW) heterojunctions, aiming for releasing the electrostatic screening effect and improving the field emission characteristics. The trade-off between the reduction in the electrostatic screening effect and the decrease of emission sites leads to an optimal SiNW bundle arrangement which enables the lowest turn-on electric field of 1.4 V/μm and highest emission current density of 191 μA/cm{sup 2} among all testing SiNW samples. Benefiting from the superior thermal and electrical properties of CNTs and the flexible patterning technologies available for SiNWs, bundle arrays of CNT–SiNW heterojunctions show improved and highly-uniform field emission with a lower turn-on electric field of 0.9 V/μm and higher emission current density of 5.86 mA/cm{sup 2}. The application of these materials and their corresponding fabrication approaches is not limited to the field emission but can be used for a variety of emerging fields like nanoelectronics, lithium-ion batteries, and solar cells. - Highlights: • Aligned silicon nanowire (SiNW) bundle arrays are realized with top-down methods. • Growing carbon nanotubes atop SiNW bundle arrays enable uniform field emission. • A turn-on field of 0.9 V/μm and an emission current of > 5 mA/cm{sup 2} are achieved.

  2. Development and implementation of a smartphone application to promote physical activity and reduce screen-time in adolescent boys.

    Science.gov (United States)

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

    2014-01-01

    To describe the development and implementation of a smartphone application (app) designed to promote physical activity and reduce screen-time in adolescent boys considered "at-risk" of obesity. 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 and evaluated using a cluster randomized controlled trial with 361 boys (12.7 ± 0.5 years) in 14 secondary schools. Following the completion of the study, participants in the intervention group completed a process evaluation questionnaire and focus groups were conducted with 42 students to explore their general perceptions of the ATLAS program and their experience with the smartphone app. Barriers and challenges encountered in the development, implementation, and evaluation of the app are also described. Participation in the study was not contingent on ownership of a smartphone, but 70% of participants in the intervention group reported having access to a smartphone or tablet device. Focus group participants reported an enjoyment of the program, and felt that it had provided them with new skills, techniques, and routines for the future. However, their engagement with the smartphone app was limited, due to a variety of reasons. Barriers to the implementation and evaluation of the app included limited access to smartphone devices, technical problems with the push notifications, lack of access to usage data, and the challenges of maintaining participants' interest in using the app. Although participants reported high levels of satisfaction with the ATLAS program in general, the smartphone app was not used extensively. Additional strategies and features may be needed to enhance engagement in adolescent boys.

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

    Directory of Open Access Journals (Sweden)

    David Revalds Lubans

    2014-05-01

    Full Text Available 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 and evaluated using a cluster randomized controlled trial with 361 boys (12.7± 0.5 years in 14 secondary schools. Following the completion of the study, participants in the intervention group completed a process evaluation questionnaire and focus groups were conducted with 42 students to explore their general perceptions of the ATLAS program and their experience with the smartphone app. Barriers and challenges encountered in the development, implementation and evaluation of the app are also described.Results: Participation in the study was not contingent on ownership of a smartphone, but 70% of participants in the intervention group reported having access to a smartphone or tablet device. Focus group participants reported an enjoyment of the program, and felt that it had provided them with new skills, techniques, and routines for the future. However, their engagement with the smartphone app was limited, due to a variety of reasons. Barriers to the implementation and evaluation of the app included limited access to smartphone devices, technical problems with the push notifications, lack of access to usage data and the challenges of maintaining participants’ interest in using the app.Conclusions: Although participants reported high levels of satisfaction with the ATLAS program in general, the smartphone app was not used extensively. Additional strategies and features may be needed to enhance engagement in adolescent boys.

  4. 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.

  5. Exploring biomolecular dynamics and interactions using advanced sampling methods

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  6. Double-gated spectral snapshots for biomolecular fluorescence

    International Nuclear Information System (INIS)

    Nakamura, Ryosuke; Hamada, Norio; Ichida, Hideki; Tokunaga, Fumio; Kanematsu, Yasuo

    2007-01-01

    A versatile method to take femtosecond spectral snapshots of fluorescence has been developed based on a double gating technique in the combination of an optical Kerr gate and an image intensifier as an electrically driven gate set in front of a charge-coupled device detector. The application of a conventional optical-Kerr-gate method is limited to molecules with the short fluorescence lifetime up to a few hundred picoseconds, because long-lifetime fluorescence itself behaves as a source of the background signal due to insufficiency of the extinction ratio of polarizers employed for the Kerr gate. By using the image intensifier with the gate time of 200 ps, we have successfully suppressed the background signal and overcome the application limit of optical-Kerr-gate method. The system performance has been demonstrated by measuring time-resolved fluorescence spectra for laser dye solution and the riboflavin solution as a typical sample of biomolecule

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

    Science.gov (United States)

    Xie, Yang; Ying, Jinyong; Xie, Dexuan

    2017-03-30

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

  8. 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

  9. Decision-making in healthcare: a practical application of partial least square path modelling to coverage of newborn screening programmes.

    Science.gov (United States)

    Fischer, Katharina E

    2012-08-02

    Decision-making in healthcare is complex. Research on coverage decision-making has focused on comparative studies for several countries, statistical analyses for single decision-makers, the decision outcome and appraisal criteria. Accounting for decision processes extends the complexity, as they are multidimensional and process elements need to be regarded as latent constructs (composites) that are not observed directly. The objective of this study was to present a practical application of partial least square path modelling (PLS-PM) to evaluate how it offers a method for empirical analysis of decision-making in healthcare. Empirical approaches that applied PLS-PM to decision-making in healthcare were identified through a systematic literature search. PLS-PM was used as an estimation technique for a structural equation model that specified hypotheses between the components of decision processes and the reasonableness of decision-making in terms of medical, economic and other ethical criteria. The model was estimated for a sample of 55 coverage decisions on the extension of newborn screening programmes in Europe. Results were evaluated by standard reliability and validity measures for PLS-PM. After modification by dropping two indicators that showed poor measures in the measurement models' quality assessment and were not meaningful for newborn screening, the structural equation model estimation produced plausible results. The presence of three influences was supported: the links between both stakeholder participation or transparency and the reasonableness of decision-making; and the effect of transparency on the degree of scientific rigour of assessment. Reliable and valid measurement models were obtained to describe the composites of 'transparency', 'participation', 'scientific rigour' and 'reasonableness'. The structural equation model was among the first applications of PLS-PM to coverage decision-making. It allowed testing of hypotheses in situations where there

  10. Decision-making in healthcare: a practical application of partial least square path modelling to coverage of newborn screening programmes

    Directory of Open Access Journals (Sweden)

    Fischer Katharina E

    2012-08-01

    Full Text Available Abstract Background Decision-making in healthcare is complex. Research on coverage decision-making has focused on comparative studies for several countries, statistical analyses for single decision-makers, the decision outcome and appraisal criteria. Accounting for decision processes extends the complexity, as they are multidimensional and process elements need to be regarded as latent constructs (composites that are not observed directly. The objective of this study was to present a practical application of partial least square path modelling (PLS-PM to evaluate how it offers a method for empirical analysis of decision-making in healthcare. Methods Empirical approaches that applied PLS-PM to decision-making in healthcare were identified through a systematic literature search. PLS-PM was used as an estimation technique for a structural equation model that specified hypotheses between the components of decision processes and the reasonableness of decision-making in terms of medical, economic and other ethical criteria. The model was estimated for a sample of 55 coverage decisions on the extension of newborn screening programmes in Europe. Results were evaluated by standard reliability and validity measures for PLS-PM. Results After modification by dropping two indicators that showed poor measures in the measurement models’ quality assessment and were not meaningful for newborn screening, the structural equation model estimation produced plausible results. The presence of three influences was supported: the links between both stakeholder participation or transparency and the reasonableness of decision-making; and the effect of transparency on the degree of scientific rigour of assessment. Reliable and valid measurement models were obtained to describe the composites of ‘transparency’, ‘participation’, ‘scientific rigour’ and ‘reasonableness’. Conclusions The structural equation model was among the first applications of PLS-PM to

  11. 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.

  12. Contemporary Use of Anomalous Diffraction in Biomolecular Structure Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Liu Q.; Hendrickson, W.

    2017-01-01

    The normal elastic X-ray scattering that depends only on electron density can be modulated by an ?anomalous? component due to resonance between X-rays and electronic orbitals. Anomalous scattering thereby precisely identifies atomic species, since orbitals distinguish atomic elements, which enables the multi- and single-wavelength anomalous diffraction (MAD and SAD) methods. SAD now predominates in de novo structure determination of biological macromolecules, and we focus here on the prevailing SAD method. We describe the anomalous phasing theory and the periodic table of phasing elements that are available for SAD experiments, differentiating between those readily accessible for at-resonance experiments and those that can be effective away from an edge. We describe procedures for present-day SAD phasing experiments and we discuss optimization of anomalous signals for challenging applications. We also describe methods for using anomalous signals as molecular markers for tracing and element identification. Emerging developments and perspectives are discussed in brief.

  13. 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

  14. Effective screening strategy using ensembled pharmacophore models combined with cascade docking: application to p53-MDM2 interaction inhibitors.

    Science.gov (United States)

    Xue, Xin; Wei, Jin-Lian; Xu, Li-Li; Xi, Mei-Yang; Xu, Xiao-Li; Liu, Fang; Guo, Xiao-Ke; Wang, Lei; Zhang, Xiao-Jin; Zhang, Ming-Ye; Lu, Meng-Chen; Sun, Hao-Peng; You, Qi-Dong

    2013-10-28

    Protein-protein interactions (PPIs) play a crucial role in cellular function and form the backbone of almost all biochemical processes. In recent years, protein-protein interaction inhibitors (PPIIs) have represented a treasure trove of potential new drug targets. Unfortunately, there are few successful drugs of PPIIs on the market. Structure-based pharmacophore (SBP) combined with docking has been demonstrated as a useful Virtual Screening (VS) strategy in drug development projects. However, the combination of target complexity and poor binding affinity prediction has thwarted the application of this strategy in the discovery of PPIIs. Here we report an effective VS strategy on p53-MDM2 PPI. First, we built a SBP model based on p53-MDM2 complex cocrystal structures. The model was then simplified by using a Receptor-Ligand complex-based pharmacophore model considering the critical binding features between MDM2 and its small molecular inhibitors. Cascade docking was subsequently applied to improve the hit rate. Based on this strategy, we performed VS on NCI and SPECS databases and successfully discovered 6 novel compounds from 15 hits with the best, compound 1 (NSC 5359), K(i) = 180 ± 50 nM. These compounds can serve as lead compounds for further optimization.

  15. A Simplified Method for Gene Knockout and Direct Screening of Recombinant Clones for Application in Paenibacillus polymyxa.

    Directory of Open Access Journals (Sweden)

    Seong-Bin Kim

    Full Text Available Paenibacillus polymyxa is a bacterium widely used in agriculture, industry, and environmental remediation because it has multiple functions including nitrogen fixation and produces various biologically active compounds. Among these compounds are the antibiotics polymyxins, and the bacterium is currently being reassessed for medical application. However, a lack of genetic tools for manipulation of P. polymyxa has limited our understanding of the biosynthesis of these compounds.To facilitate an understanding of the genetic determinants of the bacterium, we have developed a system for marker exchange mutagenesis directly on competent cells of P. polymyxa under conditions where homologous recombination is enhanced by denaturation of the suicide plasmid DNA. To test this system, we targeted P. polymyxa α-and β-amylase genes for disruption. Chloramphenicol or erythromycin resistance genes were inserted into the suicide plasmid pGEM7Z-f+ (Promega. To mediate homologous recombination and replacement of the targeted genes with the antibiotic resistance genes nucleotide sequences of the α-and β-amylase genes were cloned into the plasmid flanking the antibiotic resistance genes.We have created a simple system for targeted gene deletion in P. polymyxa E681. We propose that P. polymyxa isogenic mutants could be developed using this system of marker exchange mutagenesis. α-and β-amylase genes provide a useful tool for direct recombinant screening in P. polymyxa.

  16. Analysis of risk indicators and issues associated with applications of screening model for hazardous and radioactive waste sites

    International Nuclear Information System (INIS)

    Buck, J.W.; Strenge, D.L.; Droppo, J.G. Jr.

    1990-12-01

    Risk indicators, such as population risk, maximum individual risk, time of arrival of contamination, and maximum water concentrations, were analyzed to determine their effect on results from a screening model for hazardous and radioactive waste sites. The analysis of risk indicators is based on calculations resulting from exposure to air and waterborne contamination predicted with Multimedia Environmental Pollutant Assessment System (MEPAS) model. The different risk indicators were analyzed, based on constituent type and transport and exposure pathways. Three of the specific comparisons that were made are (1) population-based versus maximum individual-based risk indicators, (2) time of arrival of contamination, and (3) comparison of different threshold assumptions for noncarcinogenic impacts. Comparison of indicators for population- and maximum individual-based human health risk suggests that these two parameters are highly correlated, but for a given problem, one may be more important than the other. The results indicate that the arrival distribution for different levels of contamination reaching a receptor can also be helpful in decisions regarding the use of resources for remediating short- and long-term environmental problems. The addition of information from a linear model for noncarcinogenic impacts allows interpretation of results below the reference dose (RfD) levels that might help in decisions for certain applications. The analysis of risk indicators suggests that important information may be lost by the use of a single indicator to represent public health risk and that multiple indicators should be considered. 15 refs., 8 figs., 1 tab

  17. Application of MoS{sub 2} modified screen-printed electrodes for highly sensitive detection of bovine serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Kukkar, Manil [Central Scientific Instruments Organisation (CSIR-CSIO), Sector 30-C, Chandigarh, 160030 (India); Academy of Scientific and Innovative Research, CSIR-CSIO, Sector 30-C, Chandigarh, 160030 (India); Sharma, Ashish [Central Scientific Instruments Organisation (CSIR-CSIO), Sector 30-C, Chandigarh, 160030 (India); UIET, Panjab University, Sector 14, Chandigarh, 160014 (India); Kumar, Parveen [Department of Biotechnology, Kurukshetra University, Kurukshetra, 136119 (India); Kim, Ki-Hyun, E-mail: kkim61@hanyang.ac.kr [Department of Civil & Environmental Engineering, Hanyang University, 222 Wangsimni-Ro, Seoul 04763 (Korea, Republic of); Deep, Akash, E-mail: dr.akashdeep@csio.res.in [Central Scientific Instruments Organisation (CSIR-CSIO), Sector 30-C, Chandigarh, 160030 (India); Academy of Scientific and Innovative Research, CSIR-CSIO, Sector 30-C, Chandigarh, 160030 (India)

    2016-10-05

    The present work reports the application of a new molybdenum disulphide (MoS{sub 2})-based electrochemical platform for highly sensitive quantitation of an iron-binding protein, bovine serum albumin (BSA). The gold screen-printed electrodes were modified with MoS{sub 2} nanoflakes, followed by bioconjugation with anti-BSA antibodies. Using the above bioelectrode, cyclic voltammetric analysis was carried out in the presence of a Fe{sup 3+}/Fe{sup 2+} redox probe which exhibited a linear response of peak current with varying concentrations of BSA up to 10 ng/mL (with a detection limit of 0.006 ng/mL). This study is novel in that it shows a considerable enhancement of signal during electrochemical sensing of a protein. - Highlights: • MoS{sub 2} nanoflakes have been used for an electrochemical immunosensor. • The sensor's response was proportional to the antigen concentration. • Highly sensitive and specific detection of iron-binding protein ‘BSA’ is achieved. • A wide linear range of detection of BSA is demonstrated.

  18. Nonlinear mixed effects dose response modeling in high throughput drug screens: application to melanoma cell line analysis.

    Science.gov (United States)

    Ding, Kuan-Fu; Petricoin, Emanuel F; Finlay, Darren; Yin, Hongwei; Hendricks, William P D; Sereduk, Chris; Kiefer, Jeffrey; Sekulic, Aleksandar; LoRusso, Patricia M; Vuori, Kristiina; Trent, Jeffrey M; Schork, Nicholas J

    2018-01-12

    Cancer cell lines are often used in high throughput drug screens (HTS) to explore the relationship between cell line characteristics and responsiveness to different therapies. Many current analysis methods infer relationships by focusing on one aspect of cell line drug-specific dose-response curves (DRCs), the concentration causing 50% inhibition of a phenotypic endpoint (IC 50 ). Such methods may overlook DRC features and do not simultaneously leverage information about drug response patterns across cell lines, potentially increasing false positive and negative rates in drug response associations. We consider the application of two methods, each rooted in nonlinear mixed effects (NLME) models, that test the relationship relationships between estimated cell line DRCs and factors that might mitigate response. Both methods leverage estimation and testing techniques that consider the simultaneous analysis of different cell lines to draw inferences about any one cell line. One of the methods is designed to provide an omnibus test of the differences between cell line DRCs that is not focused on any one aspect of the DRC (such as the IC 50 value). We simulated different settings and compared the different methods on the simulated data. We also compared the proposed methods against traditional IC 50 -based methods using 40 melanoma cell lines whose transcriptomes, proteomes, and, importantly, BRAF and related mutation profiles were available. Ultimately, we find that the NLME-based methods are more robust, powerful and, for the omnibus test, more flexible, than traditional methods. Their application to the melanoma cell lines reveals insights into factors that may be clinically useful.

  19. Multiresolution persistent homology for excessively large biomolecular datasets

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-07

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

  20. Plucked Human Hair Shafts and Biomolecular Medical Research

    Directory of Open Access Journals (Sweden)

    Kevin Schembri

    2013-01-01

    Full Text Available The hair follicle is a skin integument at the boundary between an organism and its immediate environment. The biological role of the human hair follicle has lost some of its ancestral importance. However, an indepth investigation of this miniorgan reveals hidden complexity with huge research potential. An essential consideration when dealing with human research is the awareness of potential harm and thus the absolute need not to harm—a rule aptly qualified by the Latin term “primum non nocere” (first do no harm. The plucked hair shaft offers such advantages. The use of stem cells found in hair follicles cells is gaining momentum in the field of regenerative medicine. Furthermore, current diagnostic and clinical applications of plucked hair follicles include their use as autologous and/or three-dimensional epidermal equivalents, together with their utilization as surrogate tissue in pharmacokinetic and pharmacodynamics studies. Consequently, the use of noninvasive diagnostic procedures on hair follicle shafts, posing as a surrogate molecular model for internal organs in the individual patient for a spectrum of human disease conditions, can possibly become a reality in the near future.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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...

  6. Super-resolution biomolecular crystallography with low-resolution data.

    Science.gov (United States)

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

    2010-04-22

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

  7. 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.

  8. 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

  9. 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.

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

    Science.gov (United States)

    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.

  11. Elastic light scattering for clinical pathogens identification: application to early screening of Staphylococcus aureus on specific medium

    Science.gov (United States)

    Schultz, E.; Genuer, V.; Marcoux, P.; Gal, O.; Belafdil, C.; Decq, D.; Maurin, Max; Morales, S.

    2018-02-01

    Elastic Light Scattering (ELS) is an innovative technique to identify bacterial pathogens directly on culture plates. Compelling results have already been reported for agri-food applications. Here, we have developed ELS for clinical diagnosis, starting with Staphylococcus aureus early screening. Our goal is to bring a result (positive/negative) after only 6 h of growth to fight surgical-site infections. The method starts with the acquisition of the scattering pattern arising from the interaction between a laser beam and a single bacterial colony growing on a culture medium. Then, the resulting image, considered as the bacterial species signature, is analyzed using statistical learning techniques. We present a custom optical setup able to target bacterial colonies with various sizes (30-500 microns). This system was used to collect a reference dataset of 38 strains of S. aureus and other Staphyloccocus species (5459 images) on ChromIDSAID/ MRSA bi-plates. A validation set from 20 patients has then been acquired and clinically-validated according to chromogenic enzymatic tests. The best correct-identification rate between S. aureus and S. non-aureus (94.7%) has been obtained using a support vector machine classifier trained on a combination of Fourier-Bessel moments and Local- Binary-Patterns extracted features. This statistical model applied to the validation set provided a sensitivity and a specificity of 90.0% and 56.9%, or alternatively, a positive predictive value of 47% and a negative predictive value of 93%. From a clinical point of view, the results head in the right direction and pave the way toward the WHO's requirements for rapid, low-cost, and automated diagnosis tools.

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

    Science.gov (United States)

    Thurber, Kent R; Tycko, Robert

    2008-12-01

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

  13. 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.

  14. 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.

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

    Science.gov (United States)

    Goni, Md Osman

    2013-01-01

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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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

  2. 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)

  3. Application of Ammonium Bechromate and Potassium Bechromate as PhotoSensitive Emulsion to Sunlight Irradiation on Printing Screen for Textile

    International Nuclear Information System (INIS)

    Santoso-Sastrosoeparno

    2000-01-01

    The paste of photo sensitive emulsion that has been used in thepreparation for producing ready used printing screen contained two materials,namely the paste from monomer solution to be polymerized for strengtheningthe printing screen, and material for photo sensitive emulsion, usingammonium or potassium bichromate as common agent. From the previous studyabout producing printing screen from polyester, by using vinyl alcohol (VA)and polyvinyl acetate (PVAc) as polymeric material, as well as ammoniumbichromate as photo sensitive emulsion, has obtained the best combination forpolymer mixture from 80% of vinyl alcohol and 20% of polyvinyl acetate. Inthis research study, the same activity will be subjected to either ammoniumor potassium bichromate, with assumption that there will be differentproperties between ammonium and potassium cations which might have influenceto the printing screen from polyester. Some various mixture of VA and PVAc aspolymeric materials were carried out in this study, and to each of thepolymeric paste was added the photo sensitive emulsion, either ammoniumbe-chromate or potassium bichromate, stirring to homogeneous condition,coating the surface of flat printing screen, allow to dry in the dark room(no light), apply to sunlight irradiation for few minutes, and followed bycuring process to become ready used as printing screen. The printing screenproduced in this experiment was then subjected to various testing, such asstiffness, strength retention and shearing strength in either length andwidth directions of the screen. It was shown from the testing results thatthe coated screen with potassium bichromate as photo sensitive emulsion willgain better properties in stiffness, strength retention as well as shearingstrength, in all polymeric mixtures, compared to the ones with ammoniumbe-chromate. (author)

  4. 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

  5. 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

  6. 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/.

  7. "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.

  8. 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…

  9. 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

  10. PinAPL-Py: A comprehensive web-application for the analysis of CRISPR/Cas9 screens.

    Science.gov (United States)

    Spahn, Philipp N; Bath, Tyler; Weiss, Ryan J; Kim, Jihoon; Esko, Jeffrey D; Lewis, Nathan E; Harismendy, Olivier

    2017-11-20

    Large-scale genetic screens using CRISPR/Cas9 technology have emerged as a major tool for functional genomics. With its increased popularity, experimental biologists frequently acquire large sequencing datasets for which they often do not have an easy analysis option. While a few bioinformatic tools have been developed for this purpose, their utility is still hindered either due to limited functionality or the requirement of bioinformatic expertise. To make sequencing data analysis of CRISPR/Cas9 screens more accessible to a wide range of scientists, we developed a Platform-independent Analysis of Pooled Screens using Python (PinAPL-Py), which is operated as an intuitive web-service. PinAPL-Py implements state-of-the-art tools and statistical models, assembled in a comprehensive workflow covering sequence quality control, automated sgRNA sequence extraction, alignment, sgRNA enrichment/depletion analysis and gene ranking. The workflow is set up to use a variety of popular sgRNA libraries as well as custom libraries that can be easily uploaded. Various analysis options are offered, suitable to analyze a large variety of CRISPR/Cas9 screening experiments. Analysis output includes ranked lists of sgRNAs and genes, and publication-ready plots. PinAPL-Py helps to advance genome-wide screening efforts by combining comprehensive functionality with user-friendly implementation. PinAPL-Py is freely accessible at http://pinapl-py.ucsd.edu with instructions and test datasets.

  11. Application of Atomic Dielectric Resonance Spectroscopy for the screening of blood samples from patients with clinical variant and sporadic CJD

    Directory of Open Access Journals (Sweden)

    Ironside James W

    2007-08-01

    Full Text Available Abstract Background Sub-clinical variant Creutzfeldt-Jakob disease (vCJD infection and reports of vCJD transmission through blood transfusion emphasise the need for blood screening assays to ensure the safety of blood and transplanted tissues. Most assays aim to detect abnormal prion protein (PrPSc, although achieving required sensitivity is a challenge. Methods We have used innovative Atomic Dielectric Resonance Spectroscopy (ADRS, which determines dielectric properties of materials which are established by reflectivity and penetration of radio/micro waves, to analyse blood samples from patients and controls to identify characteristic ADR signatures unique to blood from vCJD and to sCJD patients. Initial sets of blood samples from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors were screened as training samples to determine group-specific ADR characteristics, and provided a basis for classification of blinded sets of samples. Results Blood sample groups from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors screened by ADRS were classified with 100% specificity and sensitivity, discriminating these by a co-variance expert analysis system. Conclusion ADRS appears capable of recognising and discriminating serum samples from vCJD, sCJD, non-CJD neurological diseases, and normal healthy adults, and might be developed to provide a system for primary screening or confirmatory assay complementary to other screening systems.

  12. A new stoichiometric miniaturization strategy for screening of industrial microbial strains: application to cellulase hyper-producing Trichoderma reesei strains

    Directory of Open Access Journals (Sweden)

    Jourdier Etienne

    2012-05-01

    Full Text Available Abstract Background During bioprocess development, secondary screening is a key step at the boundary between laboratory and industrial conditions. To ensure an effective high-throughput screening, miniaturized laboratory conditions must mimic industrial conditions, especially for oxygen transfer, feeding capacity and pH stabilization. Results A feeding strategy has been applied to develop a simple screening procedure, in which a stoichiometric study is combined with a standard miniaturization procedure. Actually, the knowledge of all nutriments and base or acid requirements leads to a great simplification of pH stabilization issue of miniaturized fed-batch cultures. Applied to cellulase production by Trichoderma reesei, this strategy resulted in a stoichiometric mixed feed of carbon and nitrogen sources. While keeping the pH between shake flask and stirred bioreactor comparable, the developed shake flask protocol reproduced the strain behaviour under stirred bioreactor conditions. Compared to a an already existing miniaturized shake flasks protocol, the cellulase concentration was increased 5-fold, reaching about 10 g L-1. Applied to the secondary screening of several clones, the newly developed protocol succeeded in selecting a clone with a high industrial potential. Conclusions The understanding of a bioprocess stoichiometry contributed to define a simpler and more effective miniaturization. The suggested strategy can potentially be applied to other fed-batch processes, for the screening of either strain collections or experimental conditions.

  13. Application of Atomic Dielectric Resonance Spectroscopy for the screening of blood samples from patients with clinical variant and sporadic CJD

    Science.gov (United States)

    Fagge, Timothy J; Barclay, G Robin; Stove, G Colin; Stove, Gordon; Robinson, Michael J; Head, Mark W; Ironside, James W; Turner, Marc L

    2007-01-01

    Background Sub-clinical variant Creutzfeldt-Jakob disease (vCJD) infection and reports of vCJD transmission through blood transfusion emphasise the need for blood screening assays to ensure the safety of blood and transplanted tissues. Most assays aim to detect abnormal prion protein (PrPSc), although achieving required sensitivity is a challenge. Methods We have used innovative Atomic Dielectric Resonance Spectroscopy (ADRS), which determines dielectric properties of materials which are established by reflectivity and penetration of radio/micro waves, to analyse blood samples from patients and controls to identify characteristic ADR signatures unique to blood from vCJD and to sCJD patients. Initial sets of blood samples from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) were screened as training samples to determine group-specific ADR characteristics, and provided a basis for classification of blinded sets of samples. Results Blood sample groups from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) screened by ADRS were classified with 100% specificity and sensitivity, discriminating these by a co-variance expert analysis system. Conclusion ADRS appears capable of recognising and discriminating serum samples from vCJD, sCJD, non-CJD neurological diseases, and normal healthy adults, and might be developed to provide a system for primary screening or confirmatory assay complementary to other screening systems. PMID:17760958

  14. 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

  15. 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.

  16. Calculation of the importance of quality factors in braille application process on labels by screen UV-varnishes

    Directory of Open Access Journals (Sweden)

    Vyacheslav Repeta

    2014-09-01

    Full Text Available Oriented graph has been drawn in the article according to fixed factors of the quality of applying Braille screen printing on the label by screen UV-varnishes. Using hierarchical representation of relationships between factors in the form of oriented graphs we have ranked the factors of the screen printing process of Braille elements by UV-varnishes and calculated their corresponding coefficients. We have found that the most ranked are such factors as the surface energy of the printing material, the printing speed, the temperature of UV-varnish and its viscosity. Received results of ranking will enable to synthesize the model of the process’ priority factors and to reveal the possibilities of regulations of geometrical parameters of the tactile font elements.

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

    Science.gov (United States)

    Whittaker, Kara A.; McShane, Dan

    2013-02-01

    A large storm event in southwest Washington State triggered over 2500 landslides and provided an opportunity to assess two slope stability screening tools. The statistical analysis conducted demonstrated that both screening tools are effective at predicting where landslides were likely to take place (Whittaker and McShane, 2012). Here we reply to two discussions of this article related to the development of the slope stability screening tools and the accuracy and scale of the spatial data used. Neither of the discussions address our statistical analysis or results. We provide greater detail on our sampling criteria and also elaborate on the policy and management implications of our findings and how they complement those of a separate investigation of landslides resulting from the same storm. The conclusions made in Whittaker and McShane (2012) stand as originally published unless future analysis indicates otherwise.

  18. Biomolecular characterization of wild sicilian oregano: phytochemical screening of essential oils and extracts, and evaluation of their antioxidant activities.

    Science.gov (United States)

    Tuttolomondo, Teresa; La Bella, Salvatore; Licata, Mario; Virga, Giuseppe; Leto, Claudio; Saija, Antonella; Trombetta, Domenico; Tomaino, Antonio; Speciale, Antonio; Napoli, Edoardo M; Siracusa, Laura; Pasquale, Andrea; Curcuruto, Giusy; Ruberto, Giuseppe

    2013-03-01

    An extensive survey of wild Sicilian oregano was made. A total of 57 samples were collected from various sites, followed by taxonomic characterization from an agronomic perspective. Based on morphological and production characteristics obtained from the 57 samples, cluster analysis was used to divide the samples into homogeneous groups, to identify the best biotypes. All samples were analyzed for their phytochemical content, applying a cascade-extraction protocol and hydrodistillation, to obtain the non volatile components and the essential oils, respectively. The extracts contained thirteen polyphenol derivatives, i.e., four flavanones, seven flavones, and two organic acids. Their qualitative and quantitative characterization was carried out by LC/MS analyses. The essential oils were characterized using a combination of GC-FID and GC/MS analyses; a total of 81 components were identified. The major components of the oils were thymol, p-cymene, and γ-terpinene. Cluster analysis was carried out on both phytochemical profiles and resulted in the division of the oregano samples into different chemical groups. The antioxidant activity of the essential oils and extracts was investigated by the Folin-Ciocalteau (FC) colorimetric assay, by UV radiation-induced peroxidation in liposomal membranes (UV-IP test), and by determining the O(2)(∙-)-scavenging activity. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

  19. 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)

  20. 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.

  1. 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.

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

    Science.gov (United States)

    Seibert, Jakob; Bannwarth, Christoph; Grimme, Stefan

    2017-08-30

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

  3. 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.

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

    NARCIS (Netherlands)

    Maljaars, C.E.P.

    2006-01-01

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

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  6. 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.

  7. 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

  8. The Spatial Distribution of Hepatitis C Virus Infections and Associated Determinants--An Application of a Geographically Weighted Poisson Regression for Evidence-Based Screening Interventions in Hotspots.

    Science.gov (United States)

    Kauhl, Boris; Heil, Jeanne; Hoebe, Christian J P A; Schweikart, Jürgen; Krafft, Thomas; Dukers-Muijrers, Nicole H T M

    2015-01-01

    Hepatitis C Virus (HCV) infections are a major cause for liver diseases. A large proportion of these infections remain hidden to care due to its mostly asymptomatic nature. Population-based screening and screening targeted on behavioural risk groups had not proven to be effective in revealing these hidden infections. Therefore, more practically applicable approaches to target screenings are necessary. Geographic Information Systems (GIS) and spatial epidemiological methods may provide a more feasible basis for screening interventions through the identification of hotspots as well as demographic and socio-economic determinants. Analysed data included all HCV tests (n = 23,800) performed in the southern area of the Netherlands between 2002-2008. HCV positivity was defined as a positive immunoblot or polymerase chain reaction test. Population data were matched to the geocoded HCV test data. The spatial scan statistic was applied to detect areas with elevated HCV risk. We applied global regression models to determine associations between population-based determinants and HCV risk. Geographically weighted Poisson regression models were then constructed to determine local differences of the association between HCV risk and population-based determinants. HCV prevalence varied geographically and clustered in urban areas. The main population at risk were middle-aged males, non-western immigrants and divorced persons. Socio-economic determinants consisted of one-person households, persons with low income and mean property value. However, the association between HCV risk and demographic as well as socio-economic determinants displayed strong regional and intra-urban differences. The detection of local hotspots in our study may serve as a basis for prioritization of areas for future targeted interventions. Demographic and socio-economic determinants associated with HCV risk show regional differences underlining that a one-size-fits-all approach even within small geographic

  9. Colorado SIP: 5 CCR 1001-13, Reg 11, Motor Vehicle Emissions Inspection Program—Part A, General Provisions, Area of Applicability, Schedules for Obtaining Certification of Emissions Control, Definitions, Exemptions, and Clean Screening/Remote Sensing

    Science.gov (United States)

    Colorado SIP: 5 CCR 1001-13, Reg 11, Motor Vehicle Emissions Inspection Program—Part A, General Provisions, Area of Applicability, Schedules for Obtaining Certification of Emissions Control, Definitions, Exemptions, and Clean Screening/Remote Sensing

  10. 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.

  11. Formulation and screen printing of water based conductive flake silver pastes onto green ceramic tapes for electronic applications

    International Nuclear Information System (INIS)

    Faddoul, Rita; Reverdy-Bruas, Nadège; Blayo, Anne

    2012-01-01

    Highlights: ► Formulation of water-based pastes. ► Viscosity, yield stress, elastic and viscous modulus determination. ► Screen printing onto green ceramic tapes. ► Rheology effect on line dimensions and electrical properties. ► Resistivity ∼18–33 nΩ m. Minimum width ∼60 μm after sintering. - Abstract: Environmentally friendly, water-based silver pastes, adapted for screen printing, were formulated with different silver contents (67–75%). These pastes allowed screen printing onto low temperature co-fired ceramic (LTCC) of narrow conductive tracks with a 60 μm line width and a 3 × 10 −8 Ω m electrical resistivity. Inks were formulated with a mixture of spherical and flake shape silver particles with 2–4 μm mean diameter. Rheological behaviour of pastes was studied in order to determine its effect on printed lines properties. Prepared inks were then screen printed and sintered under normal atmosphere at 875 °C. As expected, electrical properties depended on silver content. Resistivity values varying from 1.6 × 10 −8 to 3.3 × 10 −8 Ω m were calculated over 36.3 cm line length. These values are very close to bulk silver resistivity (1.6 × 10 −8 Ω m). Compared to previous research and commercial pastes, the newly formulated pastes reached equivalent or even better conductivities with lower silver content (70% by weight).

  12. Sulfide perovskites for solar energy conversion applications: computational screening and synthesis of the selected compound LaYS3

    DEFF Research Database (Denmark)

    Kuhar, Korina; Crovetto, Andrea; Pandey, Mohnish

    2017-01-01

    of ternary sulfides followed by synthesis and confirmation of the properties of one of the most promising materials. The screening focusses on materials with ABS3 composition taking both perovskite and non-perovskite structures into consideration, and the material selection is based on descriptors...

  13. Application of Fragment Ion Information as Further Evidence in Probabilistic Compound Screening Using Bayesian Statistics and Machine Learning

    NARCIS (Netherlands)

    Woldegebriel, Michael; Zomer, Paul; Mol, Hans G.J.; Vivó-Truyols, Gabriel

    2016-01-01

    In this work, we introduce an automated, efficient, and elegant model to combine all pieces of evidence (e.g., expected retention times, peak shapes, isotope distributions, fragment-to-parent ratio) obtained from liquid chromatography-tandem mass spectrometry (LC-MS/MS/MS) data for screening

  14. Toxicology screen

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003578.htm Toxicology screen To use the sharing features on this page, please enable JavaScript. A toxicology screen refers to various tests that determine the ...

  15. 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...

  16. HERCA WG Medical Applications / WP justification. Survey about the situation in Europe regarding the use of CT on asymptomatic individuals outside screening programs

    International Nuclear Information System (INIS)

    2013-06-01

    In recent years, commercial services offering CT scans to individuals for the detection of lung, cardiac and colorectal disease has been reported in the USA and in some parts of Europe (e.g. Germany and the UK). Some of these private services are associated with aggressive advertisement and are in conflict with the general principle of justification. Faced with this situation, in July 2012, HERCA WG Medical Applications launched a survey about the situation in Europe regarding the use of CT on asymptomatic individuals outside screening programs for group 2.c. This document presents the results of the survey

  17. 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.

  18. Accurate collision integrals for the attractive static screened Coulomb potential with application to electrical conductivity. [For white dwarf stars

    Energy Technology Data Exchange (ETDEWEB)

    Macdonald, J. (Delaware, University, Newark (USA))

    1991-05-01

    The results of accurate calculations of collision integrals for the attractive static screened Coulomb potential are presented. To obtain high accuracy with minimal computational cost, the integrals are evaluated by a quadrature method based on the Whittaker cardinal function. The collision integrals for the attractive potential are needed for calculation of the electrical conductivity of a dense fully or partially ionized plasma, and the results presented here are appropriate for the conditions in the nondegenerate envelopes of white dwarf stars. 25 refs.

  19. Effect of sintering temperatures and screen printing types on TiO2 layers in DSSC applications

    Science.gov (United States)

    Supriyanto, Agus; Furqoni, Lutfi; Nurosyid, Fahru; Hidayat, Jojo; Suryana, Risa

    2016-03-01

    Dye-Sensitized Solar Cell (DSSC) is a candidate solar cell, which has a big potential in the future due to its eco-friendly material. This research is conducted to study the effect of sintering temperature and the type of screen-printing toward the characteristics of TiO2 layer as a working electrode in DSSC. TiO2 layers were fabricated using a screen-printing method with a mesh size of T-49, T-55, and T-61. TiO2 layers were sintered at temperatures of 600°C and 650°C for 60 min. DSSC structure was composed of TiO2 as semiconductors, ruthenium complex as dyes, and carbon as counter electrodes. The morphology of TiO2 layer was observed by using Nikon E2 Digital Camera Microscopy. The efficiencies of DSSC were calculated from the I-V curves. The highest efficiency is 0.015% at TiO2 layer fabricated with screen type T-61 and at a sintering temperature of 650°C.

  20. Effect of sintering temperatures and screen printing types on TiO{sub 2} layers in DSSC applications

    Energy Technology Data Exchange (ETDEWEB)

    Supriyanto, Agus; Furqoni, Lutfi; Nurosyid, Fahru, E-mail: nurosyid@yahoo.com; Suryana, Risa [Department of Physics, Faculty of Mathematics and Natural Sciences, Sebel as Maret University Jl. Ir. Sutami 36A Kentingan Surakarta 57126 (Indonesia); Hidayat, Jojo [Research Center for Electronics and Telecommunication, Indonesian Institute of Sciences (PPET-LIPI) Kampus LIPI Gd. 20 Jl. Sangkuriang Bandung (Indonesia)

    2016-03-29

    Dye-Sensitized Solar Cell (DSSC) is a candidate solar cell, which has a big potential in the future due to its eco-friendly material. This research is conducted to study the effect of sintering temperature and the type of screen-printing toward the characteristics of TiO{sub 2} layer as a working electrode in DSSC. TiO{sub 2} layers were fabricated using a screen-printing method with a mesh size of T-49, T-55, and T-61. TiO{sub 2} layers were sintered at temperatures of 600°C and 650°C for 60 min. DSSC structure was composed of TiO{sub 2} as semiconductors, ruthenium complex as dyes, and carbon as counter electrodes. The morphology of TiO{sub 2} layer was observed by using Nikon E2 Digital Camera Microscopy. The efficiencies of DSSC were calculated from the I-V curves. The highest efficiency is 0.015% at TiO{sub 2} layer fabricated with screen type T-61 and at a sintering temperature of 650°C.

  1. Effect of sintering temperatures and screen printing types on TiO_2 layers in DSSC applications

    International Nuclear Information System (INIS)

    Supriyanto, Agus; Furqoni, Lutfi; Nurosyid, Fahru; Suryana, Risa; Hidayat, Jojo

    2016-01-01

    Dye-Sensitized Solar Cell (DSSC) is a candidate solar cell, which has a big potential in the future due to its eco-friendly material. This research is conducted to study the effect of sintering temperature and the type of screen-printing toward the characteristics of TiO_2 layer as a working electrode in DSSC. TiO_2 layers were fabricated using a screen-printing method with a mesh size of T-49, T-55, and T-61. TiO_2 layers were sintered at temperatures of 600°C and 650°C for 60 min. DSSC structure was composed of TiO_2 as semiconductors, ruthenium complex as dyes, and carbon as counter electrodes. The morphology of TiO_2 layer was observed by using Nikon E2 Digital Camera Microscopy. The efficiencies of DSSC were calculated from the I-V curves. The highest efficiency is 0.015% at TiO_2 layer fabricated with screen type T-61 and at a sintering temperature of 650°C.

  2. 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 ...

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Assessing the special need for protection of vulnerable refugees: testing the applicability of a screening method (RHS-15) to detect traumatic disorders in a refugee sample in Germany.

    Science.gov (United States)

    Stingl, Markus; Knipper, Michael; Hetzger, Björge; Richards, Jessica; Yazgan, Bülent; Gallhofer, Bernd; Hanewald, Bernd

    2017-10-29

    Although EU member states are obligated to take special account of the situation of particularly vulnerable refugees, appropriate and specific measures to detect affected asylum seekers are not yet available. This study tries to pave the way for the implementation of an adequate instrument which at the same time assesses these needs of suffering people whilst responding to the need for mental health assessments specifically designed for refugees. This was done by testing the implementation of a screening method (Refugee Health Screener RHS-15) for trauma related mental health problems in refugees. Two refugee samples in Germany (differing in arrival time: 126 applicants for asylum residing in the initial reception center and 116 living in long term communal accommodations) were assessed with the culturally sensitive Refugee Health Screener (RHS-15) to detect the incidence of mental health problems amongst them. Test fairness, reasonableness, susceptibility, transparency, acceptance, external design, utility and economy of the instrument were examined to check the applicability of the RHS-15 standardization test. The RHS-15 indicates a good practical feasibility as the examination of the focused psychometric characteristics suggests. It became apparent, that implementing a screening procedure depends on political, legal and medical context factors that need to be considered. 2/3 of the participants had a positive screening result, which needs further diagnostic clarification in a second step. The RHS-15 seems to be practicable, economical, and rapidly deployable for the widespread detection of traumatic disorders in refugees living in Europe. The tool proved useful to aid diagnostic assessments and provide treatment to individuals in need, however the time of examination (resp. the duration of staying in the target land) influences the results.

  8. Experimental screening of porous materials for high pressure gas adsorption and evaluation in gas separations: application to MOFs (MIL-100 and CAU-10).

    Science.gov (United States)

    Wiersum, Andrew D; Giovannangeli, Christophe; Vincent, Dominique; Bloch, Emily; Reinsch, Helge; Stock, Norbert; Lee, Ji Sun; Chang, Jong-San; Llewellyn, Philip L

    2013-02-11

    A high-throughput gas adsorption apparatus is presented for the evaluation of adsorbents of interest in gas storage and separation applications. This instrument is capable of measuring complete adsorption isotherms up to 40 bar on six samples in parallel using as little as 60 mg of material. Multiple adsorption cycles can be carried out and four gases can be used sequentially, giving as many as 24 adsorption isotherms in 24 h. The apparatus has been used to investigate the effect of metal center (MIL-100) and functional groups (CAU-10) on the adsorption of N(2), CO(2), and light hydrocarbons on MOFs. This demonstrates how it can serve to evaluate sample quality and adsorption reversibility, to determine optimum activation conditions and to estimate separation properties. As such it is a useful tool for the screening of novel adsorbents for different applications in gas separation, providing significant time savings in identifying potentially interesting materials.

  9. Effect of binder properties on electrochemical performance for silicon-graphite anode: Method and application of binder screening

    International Nuclear Information System (INIS)

    Yim, Taeeun; Choi, Soo Jung; Jo, Yong Nam; Kim, Tae-Hyun; Kim, Ki Jae; Jeong, Goojin; Kim, Young-Jun

    2014-01-01

    Highlights: • Binder properties are systematically characterized to estimate their suitability. • Interpretation of binder properties in connection with binding affinity, electrode properties, and degree of phase separation in slurry. • According to the screening results, hybridization of poly(acrylic acid) and poly(amide imide) is recommended. • The modified binder showed improved cycle performance based on enhanced binder properties. - Abstract: With increasing demand for lithium-ion batteries (LIBs) with high energy density, silicon-based negative electrode material has attracted much interest because of its high specific capacity. Practical utilization of Si remains unattainable, however, owing to severe volume expansion in the electrode, resulting in a loss of the electrical Si network, which is directly connected to drastic capacity fading of the cell. Therefore, there have been systematic studies on the characterization of fundamental binder properties to estimate the suitability of various binder materials. The binder properties are subdivided into mechanical and adhesion characteristics, electrode properties (rigidity and recovery), and phase separation behavior of slurry to correlate with the electrochemical performance and practical acceptance of candidate materials. Systematic screening showed that hybridization of poly(acrylic acid) (PAA) and poly(amide imide) (PAI) could complement each other's properties and the hybridized PAA–PAI was synthesized by a one-step, acid-catalyzed reaction. The PAA–PAI hybrid showed enhancement in overall properties as a result of co-polymerization and exhibited remarkable cycling performance after 300 cycles. Based on these results, it can be concluded that an understanding of binder characteristics provides useful insight into the search for a more efficient binder material, and fine tuning of fundamental binder properties through screening will be advantageous to the construction of more efficient LIB

  10. An unbiased method to build benchmarking sets for ligand-based virtual screening and its application to GPCRs.

    Science.gov (United States)

    Xia, Jie; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren; Wang, Xiang Simon

    2014-05-27

    Benchmarking data sets have become common in recent years for the purpose of virtual screening, though the main focus had been placed on the structure-based virtual screening (SBVS) approaches. Due to the lack of crystal structures, there is great need for unbiased benchmarking sets to evaluate various ligand-based virtual screening (LBVS) methods for important drug targets such as G protein-coupled receptors (GPCRs). To date these ready-to-apply data sets for LBVS are fairly limited, and the direct usage of benchmarking sets designed for SBVS could bring the biases to the evaluation of LBVS. Herein, we propose an unbiased method to build benchmarking sets for LBVS and validate it on a multitude of GPCRs targets. To be more specific, our methods can (1) ensure chemical diversity of ligands, (2) maintain the physicochemical similarity between ligands and decoys, (3) make the decoys dissimilar in chemical topology to all ligands to avoid false negatives, and (4) maximize spatial random distribution of ligands and decoys. We evaluated the quality of our Unbiased Ligand Set (ULS) and Unbiased Decoy Set (UDS) using three common LBVS approaches, with Leave-One-Out (LOO) Cross-Validation (CV) and a metric of average AUC of the ROC curves. Our method has greatly reduced the "artificial enrichment" and "analogue bias" of a published GPCRs benchmarking set, i.e., GPCR Ligand Library (GLL)/GPCR Decoy Database (GDD). In addition, we addressed an important issue about the ratio of decoys per ligand and found that for a range of 30 to 100 it does not affect the quality of the benchmarking set, so we kept the original ratio of 39 from the GLL/GDD.

  11. Application of automated image analysis reduces the workload of manual screening of sentinel Lymph node biopsies in breast cancer

    DEFF Research Database (Denmark)

    Holten-Rossing, Henrik; Talman, Maj-Lis Møller; Jylling, Anne Marie Bak

    2017-01-01

    axilla. In patients with no clinical signs of metastatic disease in the axilla, a SLN biopsy (SLNB) is performed. Assessment of metastases in the SLNB is done in a conventional microscope by manually observing a metastasis and measuring its size and/or counting the number of tumor cells. This is done...... essentially to categorize the type of metastases as macrometastases, micrometastases or isolated tumor cells, which is used to determine which treatment the breast cancer patient will benefit mostly from. The aim of this study was to evaluate whether digital image analysis can be applied as a screening tool...

  12. 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.

  13. Operationalization and application of “early warning signs” to screen nanomaterials for harmful properties operationalizationand application of “early warning signs” to screen nanomaterials for harmful properties

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Nielsen, K. N.; Knudsen, N.

    endeavors. This paper explores ho w the first lesson - “Acknowledge and respond to ignorance, uncertainty and risk in techn ology appraisal” could be applied to screen nanomaterials. In cases of ignorance, uncertainty a nd risk, the EEA recommends paying particular attention to important warning signs suc h...... as novelty, persistency, whether materials are readily dispersed in the environment, whether t hey bioaccumulate or lead to potentially irreversible action. Through an analysis of these c riteria using five well-known nanomaterials (titanium dioxide, carbon nanotubes, liposomes, pol y(lactic-co-glycolic acid....... Finally, we discuss how these warning sig ns can be used by different stakeholders such as nanomaterial researchers and developers, compani es and regulators to design benign nanomaterials, communicate what is known about nano -risks and decide on whether to implement precautionary regulatory measures....

  14. General unknown screening procedure for the characterization of human drug metabolites in forensic toxicology: applications and constraints.

    Science.gov (United States)

    Sauvage, François-Ludovic; Picard, Nicolas; Saint-Marcoux, Franck; Gaulier, Jean-Michel; Lachâtre, Gérard; Marquet, Pierre

    2009-09-01

    LC coupled to single (LC-MS) and tandem (LC-MS/MS) mass spectrometry is recognized as the most powerful analytical tools for metabolic studies in drug discovery. In this article, we describe five cases illustrating the utility of screening xenobiotic metabolites in routine analysis of forensic samples using LC-MS/MS. Analyses were performed using a previously published LC-MS/MS general unknown screening (GUS) procedure developed using a hybrid linear IT-tandem mass spectrometer. In each of the cases presented, the presence of metabolites of xenobiotics was suspected after analyzing urine samples. In two cases, the parent drug was also detected and the metabolites were merely useful to confirm drug intake, but in three other cases, metabolite detection was of actual forensic interest. The presented results indicate that: (i) the GUS procedure developed is useful to detect a large variety of drug metabolites, which would have been hardly detected using targeted methods in the context of clinical or forensic toxicology; (ii) metabolite structure can generally be inferred from their "enhanced" product ion scan spectra; and (iii) structure confirmation can be achieved through in vitro metabolic experiments or through the analysis of urine samples from individuals taking the parent drug.

  15. 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.

  16. 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.

  17. 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.

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

    Science.gov (United States)

    Mairet, Francis

    2018-02-01

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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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/

  4. 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.

  5. 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.

  6. Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Mads S. Bergholt

    2017-12-01

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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Novel heparan sulfate assay by using automated high-throughput mass spectrometry: Application to monitoring and screening for mucopolysaccharidoses.

    Science.gov (United States)

    Shimada, Tsutomu; Kelly, Joan; LaMarr, William A; van Vlies, Naomi; Yasuda, Eriko; Mason, Robert W; Mackenzie, William; Kubaski, Francyne; Giugliani, Roberto; Chinen, Yasutsugu; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji E; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

    2014-01-01

    Mucopolysaccharidoses (MPS) are caused by deficiency of one of a group of specific lysosomal enzymes, resulting in excessive accumulation of glycosaminoglycans (GAGs). We previously developed GAG assay methods using liquid chromatography tandem mass spectrometry (LC-MS/MS); however, it takes 4-5 min per sample for analysis. For the large numbers of samples in a screening program, a more rapid process is desirable. The automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) integrates a solid phase extraction robot to concentrate and desalt samples prior to direction into the MS/MS without chromatographic separation; thereby allowing each sample to be processed within 10s (enabling screening of more than one million samples per year). The aim of this study was to develop a higher throughput system to assay heparan sulfate (HS) using HT-MS/MS, and to compare its reproducibility, sensitivity and specificity with conventional LC-MS/MS. HS levels were measured in the blood (plasma and serum) from control subjects and patients with MPS II, III, or IV and in dried blood spots (DBS) from newborn controls and patients with MPS I, II, or III. Results obtained from HT-MS/MS showed 1) that there was a strong correlation of levels of disaccharides derived from HS in the blood, between those calculated using conventional LC-MS/MS and HT-MS/MS, 2) that levels of HS in the blood were significantly elevated in patients with MPS II and III, but not in MPS IVA, 3) that the level of HS in patients with a severe form of MPS II was higher than that in an attenuated form, 4) that reduction of blood HS level was observed in MPS II patients treated with enzyme replacement therapy or hematopoietic stem cell transplantation, and 5) that levels of HS in newborn DBS were elevated in patients with MPS I, II or III, compared to those of control newborns. In conclusion, HT-MS/MS provides much higher throughput than LC-MS/MS-based methods with similar sensitivity and specificity

  16. Establish an automated flow injection ESI-MS method for the screening of fragment based libraries: Application to Hsp90.

    Science.gov (United States)

    Riccardi Sirtori, Federico; Caronni, Dannica; Colombo, Maristella; Dalvit, Claudio; Paolucci, Mauro; Regazzoni, Luca; Visco, Carlo; Fogliatto, Gianpaolo

    2015-08-30

    ESI-MS is a well established technique for the study of biopolymers (nucleic acids, proteins) and their non covalent adducts, due to its capacity to detect ligand-target complexes in the gas phase and allows inference of ligand-target binding in solution. In this article we used this approach to investigate the interaction of ligands to the Heat Shock Protein 90 (Hsp90). This enzyme is a molecular chaperone involved in the folding and maturation of several proteins which has been subjected in the last years to intensive drug discovery efforts due to its key role in cancer. In particular, reference compounds, with a broad range of dissociation constants from 40pM to 100μM, were tested to assess the reliability of ESI-MS for the study of protein-ligand complexes. A good agreement was found between the values measured with a fluorescence polarization displacement assay and those determined by mass spectrometry. After this validation step we describe the setup of a medium throughput screening method, based on ESI-MS, suitable to explore interactions of therapeutic relevance biopolymers with chemical libraries. Our approach is based on an automated flow injection ESI-MS method (AFI-MS) and has been applied to screen the Nerviano Medical Sciences proprietary fragment library of about 2000 fragments against Hsp90. In order to discard false positive hits and to discriminate those of them interacting with the N-terminal ATP binding site, competition experiments were performed using a reference inhibitor. Gratifyingly, this group of hits matches with the ligands previously identified by NMR FAXS techniques and confirmed by X-ray co-crystallization experiments. These results support the use of AFI-MS for the screening of medium size libraries, including libraries of small molecules with low affinity typically used in fragment based drug discovery. AFI-MS is a valid alternative to other techniques with the additional opportunities to identify compounds interacting with

  17. Screening of yeasts associated with food from the Sudan and their possible application for single cell protein and ethanol production

    Energy Technology Data Exchange (ETDEWEB)

    Hamad, S H

    1986-06-18

    In a screening program carried out in the Sudan, 200 pure yeast cultures were isolated and analysed. In a series of fermentations the kinetic parameters and the chemical composition of C.Kefyr were tested. The kinetic parameters identified for C. Kefyr in a bioreactor with 10 l working volume were used to simulate a fed batch cultivation in a 30 m/sup 3/ bioreactor with different values for the volumetric mass transfer coefficient of oxygen. Heat production and oxygen requirement were under the critical values calculated throughout the simulation. The ability of C. Kefyr to produce and tolerate ethanol at different fermentation temperatures was tested in shake flasks experiments. These experiments showed that C. Kefyr can produce and tolerate up to 10% V/V ethanol at the fermentation temperature of 40/sup 0/C. (MBC)

  18. Fast screening of glycosaminoglycan disaccharides by fluorophore-assisted carbohydrate electrophoresis (FACE): applications to biologic samples and pharmaceutical formulations.

    Science.gov (United States)

    Karousou, Evgenia; Asimakopoulou, Athanasia P; Zafeiropoulou, Vassiliki; Viola, Manuela; Monti, Luca; Rossi, Antonio; Passi, Alberto; Karamanos, Nikos

    2015-01-01

    Hyaluronan (HA), chondroitin sulfate (CS), and heparan sulfate (HS) are glycosaminoglycans (GAGs) with a great importance in biological processes as they participate in functional cell properties, such as migration, adhesion, and proliferation. A perturbation of the quantity and/or the sulfation of GAGs is often associated with pathological conditions. In this chapter, we present valuable and validated protocols for the analysis of HA-, CS-, and HS-derived disaccharides after derivatization with 2-aminoacridone and by using the fluorophore-assisted carbohydrate electrophoresis (FACE). FACE is a well-known technique and a reliable tool for a fast screening of GAGs, as it is possible to analyze 16 samples at the same time with one electrophoretic apparatus. The protocols for the gel preparation are based on the variations of the acrylamide/bisacrylamide and buffer concentrations. Different approaches for the extraction and purification of the disaccharides of various biologic samples and pharmaceutical preparations are also stressed.

  19. Clinical application of low-dose CT combined with computer-aided detection in lung cancer screening

    International Nuclear Information System (INIS)

    Xu Zushan; Hou Hongjun; Xu Yan; Ma Daqing

    2010-01-01

    Objective: To investigate the clinical value of chest low-dose CT (LDCT) combined with computer-aided detection (CAD) system for lung cancer screening in high risk population. Methods: Two hundred and nineteen healthy candidates underwent 64-slice LDCT scan. All images were reviewed in consensus by two radiologists with 15 years of thoracic CT diagnosis experience. Then the image data were analyzed with CAD alone. Finally images were reviewed by two radiologists with 5 years of CT diagnosis experience with and without CT Viewer software. The sensitivity, false positive rate of CAD for pulmonary nodule detection were calculated. SPSS 11.5 software and Chi-square test were used for the statistics. Results: Of 219 candidates ,104(47.5% ) were detected with lung nodules. There were 366 true nodules confirmed by the senior radiologists. The CAD system detected 271 (74.0%) true nodules and 424 false-positive nodules. The false-positive rate was 1.94/per case. The two junior radiologists indentifid 292 (79.8%), 286(78.1%) nodules without CAD and 336 (91.8%), 333 (91.0%) nodules with CAD respectively. There were significant differences for radiologists in indentifying nodules with or without CAD system (P<0.01). Conclusions: CAD is more sensitive than radiologists for indentifying the nodules in the central area or in the hilar region of the lung. While radiologists are more sensitive for the peripheral and sub-pleural nodules,or ground glass opacity nodules, or nodules smaller than 4 mm. CAD can not be used alone. The detection rate can be improved with the combination of radiologist and CAD in LDCT screen. (authors)

  20. Topics on distance correlation, feature screening and lifetime expectancy with application to Beaver Dam eye study data

    Science.gov (United States)

    Kong, Jing

    This thesis includes 4 pieces of work. In Chapter 1, we present the work with a method for examining mortality as it is seen to run in families, and lifestyle factors that are also seen to run in families, in a subpopulation of the Beaver Dam Eye Study that has died by 2011. We find significant distance correlations between death ages, lifestyle factors, and family relationships. Considering only sib pairs compared to unrelated persons, distance correlation between siblings and mortality is, not surprisingly, stronger than that between more distantly related family members and mortality. Chapter 2 introduces a feature screening procedure with the use of distance correlation and covariance. We demonstrate a property for distance covariance, which is incorporated in a novel feature screening procedure based on distance correlation as a stopping criterion. The approach is further implemented to two real examples, namely the famous small round blue cell tumors data and the Cancer Genome Atlas ovarian cancer data Chapter 3 pays attention to the right censored human longevity data and the estimation of lifetime expectancy. We propose a general framework of backward multiple imputation for estimating the conditional lifetime expectancy function and the variance of the estimator in the right censoring setting and prove the properties of the estimator. In addition, we apply the method to the Beaver Dam eye study data to study human longevity, where the expected human lifetime are modeled with smoothing spline ANOVA based on the covariates including baseline age, gender, lifestyle factors and disease variables. Chapter 4 compares two imputation methods for right censored data, namely the famous Buckley-James estimator and the backward imputation method proposed in Chapter 3 and shows that backward imputation method is less biased and more robust with heterogeneity.

  1. Nano carbon black-based screen printed sensor for carbofuran, isoprocarb, carbaryl and fenobucarb detection: application to grain samples.

    Science.gov (United States)

    Della Pelle, Flavio; Angelini, Claudia; Sergi, Manuel; Del Carlo, Michele; Pepe, Alessia; Compagnone, Dario

    2018-08-15

    An electrochemical screening assay for the detection of phenyl carbamates (i.e. carbaryl, carbofuran, isoprocarb and fenobucarb) was developed and applied to grains samples (i.e. durum wheat, soft wheat and maize). Nano carbon black (CB) was strategically employed to realize an effective, reproducible, fouling resistant, low cost, delocalisable screen printed sensor (CB-SPE). CB-SPEs morphology (SEM and FEM) and electrochemical property (CV and EIS) were studied. The final pesticides analysis protocol consist of: (i) extraction of the analyte (just by mixing), (ii) alkaline hydrolysis (10 min R.T.), (iii) DPV detection directly of 100 µL of extract on the CB-SPE surface. Linear range between 1.0 × 10 -7 and 1.0 × 10 -4 mol L -1 , good determination coefficients (R 2 ≥ 0.9971) and satisfactory sensitivity (≥ 3.90 × 10 -1 A M -1 cm -2 ) and LODs (≤ 8.0 × 10 -8 mol L -1 ) were obtained for all the analytes. Excellent recoveries (78-102%) and accuracy (relative error vs. HPLC-MS/MS between 9.0% and -7.8%) resulted from the analysis of grains samples. The proposed CB-SPE based approach has demonstrated to be able to detect carbaryl at Maximum residue limits levels (MRLs), allowing class selective detection of commonly employed phenyl carbamates in food samples. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. A Practical Standardized Composite Nutrition Score Based on Lean Tissue Index: Application in Nutrition Screening and Prediction of Outcome in Hemodialysis Population.

    Science.gov (United States)

    Chen, Huan-Sheng; Cheng, Chun-Ting; Hou, Chun-Cheng; Liou, Hung-Hsiang; Chang, Cheng-Tsung; Lin, Chun-Ju; Wu, Tsai-Kun; Chen, Chang-Hsu; Lim, Paik-Seong

    2017-07-01

    Rapid screening and monitoring of nutritional status is mandatory in hemodialysis population because of the increasingly encountered nutritional problems. Considering the limitations of previous composite nutrition scores applied in this population, we tried to develop a standardized composite nutrition score (SCNS) using low lean tissue index as a marker of protein wasting to facilitate clinical screening and monitoring and to predict outcome. This retrospective cohort used 2 databases of dialysis populations from Taiwan between 2011 and 2014. First database consisting of data from 629 maintenance hemodialysis patients was used to develop the SCNS and the second database containing data from 297 maintenance hemodialysis patients was used to validate this developed score. SCNS containing albumin, creatinine, potassium, and body mass index was developed from the first database using low lean tissue index as a marker of protein wasting. When applying this score in the original database, significantly higher risk of developing protein wasting was found for patients with lower SCNS (odds ratio 1.38 [middle tertile vs highest tertile, P < .0001] and 2.40 [lowest tertile vs middle tertile, P < .0001]). The risk of death was also shown to be higher for patients with lower SCNS (hazard ratio 4.45 [below median level vs above median level, P < .0001]). These results were validated in the second database. We developed an SCNS consisting of 4 easily available biochemical parameters. This kind of scoring system can be easily applied in different dialysis facilities for screening and monitoring of protein wasting. The wide application of body composition monitor in dialysis population will also facilitate the development of specific nutrition scoring model for individual facility. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  3. Poloxamer-Based Thermoreversible Gel for Topical Delivery of Emodin: Influence of P407 and P188 on Solubility of Emodin and Its Application in Cellular Activity Screening

    Directory of Open Access Journals (Sweden)

    Eunmi Ban

    2017-02-01

    Full Text Available Emodin is a component in a Chinese herb, Rheum officinale Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery of emodin. The present study was to understand the effect of poloxamer type on emodin solubility and its application in cellular activity screening. Various gel formulations composed of poloxamer 407 (P407, poloxamer 188 (P188 and PEG400 were prepared and evaluated. Major evaluation parameters were the gelation temperature (Tgel and solubility of emodin. The emodin solubility increased with increasing poloxamer concentration and the Tgel was modulated by the proper combination of P407. In particular, this study showed that the amount of P407 in thermoreversible poloxamer gel (PG was the dominant factor in enhancing solubility and P188 was effective at fixing gelation temperature in the desired range. A thermoreversible emodin PG was selected as the proper composition with the liquid state at room temperature and gel state at body temperature. The gel showed the solubility enhancement of emodin at least 100-fold compared to 10% ethanol or water. The thermoreversible formulation was applied for in vitro cellular activity screening in the human dermal fibroblast cell line and DLD-1 colon cancer cell line after dilution with cell culture media. The thermoreversible gel formulation remained as a clear solution in the microplate, which allowed reliable cellular activity screening. In contrast, emodin solution in ethanol or DMSO showed precipitation at the corresponding emodin concentration, complicating data interpretation. In conclusion, the gel formulation is proposed as a useful prototype topical formulation for testing emodin in vivo as well as in vitro.

  4. Screen printing of a capacitive cantilever-based motion sensor on fabric using a novel sacrificial layer process for smart fabric applications

    International Nuclear Information System (INIS)

    Wei, Yang; Torah, Russel; Yang, Kai; Beeby, Steve; Tudor, John

    2013-01-01

    Free-standing cantilevers have been fabricated by screen printing sacrificial and structural layers onto a standard polyester cotton fabric. By printing additional conductive layers, a complete capacitive motion sensor on fabric using only screen printing has been fabricated. This type of free-standing structure cannot currently be fabricated using conventional fabric manufacturing processes. In addition, compared to conventional smart fabric fabrication processes (e.g. weaving and knitting), screen printing offers the advantages of geometric design flexibility and the ability to simultaneously print multiple devices of the same or different designs. Furthermore, a range of active inks exists from the printed electronics industry which can potentially be applied to create many types of smart fabric. Four cantilevers with different lengths have been printed on fabric using a five-layer structure with a sacrificial material underneath the cantilever. The sacrificial layer is subsequently removed at 160 °C for 30 min to achieve a freestanding cantilever above the fabric. Two silver electrodes, one on top of the cantilever and the other on top of the fabric, are used to capacitively detect the movement of the cantilever. In this way, an entirely printed motion sensor is produced on a standard fabric. The motion sensor was initially tested on an electromechanical shaker rig at a low frequency range to examine the linearity and the sensitivity of each design. Then, these sensors were individually attached to a moving human forearm to evaluate more representative results. A commercial accelerometer (Microstrain G-link) was mounted alongside for comparison. The printed sensors have a similar motion response to the commercial accelerometer, demonstrating the potential of a printed smart fabric motion sensor for use in intelligent clothing applications. (paper)

  5. Screen printing of a capacitive cantilever-based motion sensor on fabric using a novel sacrificial layer process for smart fabric applications

    Science.gov (United States)

    Wei, Yang; Torah, Russel; Yang, Kai; Beeby, Steve; Tudor, John

    2013-07-01

    Free-standing cantilevers have been fabricated by screen printing sacrificial and structural layers onto a standard polyester cotton fabric. By printing additional conductive layers, a complete capacitive motion sensor on fabric using only screen printing has been fabricated. This type of free-standing structure cannot currently be fabricated using conventional fabric manufacturing processes. In addition, compared to conventional smart fabric fabrication processes (e.g. weaving and knitting), screen printing offers the advantages of geometric design flexibility and the ability to simultaneously print multiple devices of the same or different designs. Furthermore, a range of active inks exists from the printed electronics industry which can potentially be applied to create many types of smart fabric. Four cantilevers with different lengths have been printed on fabric using a five-layer structure with a sacrificial material underneath the cantilever. The sacrificial layer is subsequently removed at 160 °C for 30 min to achieve a freestanding cantilever above the fabric. Two silver electrodes, one on top of the cantilever and the other on top of the fabric, are used to capacitively detect the movement of the cantilever. In this way, an entirely printed motion sensor is produced on a standard fabric. The motion sensor was initially tested on an electromechanical shaker rig at a low frequency range to examine the linearity and the sensitivity of each design. Then, these sensors were individually attached to a moving human forearm to evaluate more representative results. A commercial accelerometer (Microstrain G-link) was mounted alongside for comparison. The printed sensors have a similar motion response to the commercial accelerometer, demonstrating the potential of a printed smart fabric motion sensor for use in intelligent clothing applications.

  6. Helical CT for lung-cancer screening. 3. Fundamental study for ultra-low-dose CT by application of small tube current and filter

    International Nuclear Information System (INIS)

    Itoh, Shigeki; Koyama, Shuji; Tusaka, Masatoshi; Maekoshi, Hisashi; Satake, Hiroko; Ishigaki, Takeo.

    1996-01-01

    In order to develop ultra-low-dose helical CT for lung cancer screening, the effect of reduction of the tube current to 20 mA and application of a 10 mm thick aluminium filter upon radiation dose and image quality was evaluated with a phantom. Exposure dose at the center of a gantry and absorbed dose at the center of an acrylic phantom at 20 mA with the filter were 15% and 29% of the dose at 50 mA without the filter, respectively. For reduction of absorbed dose, reduction of the tube current was more useful than application of the filter. Image noise at 20 mA with the filter was double that at 50 mA without the filter. Neither reduction of the tube current nor application of the filter changed full width at half maximum on section sensitivity of the Z-axis. Although reduction of the tube current did not affect the difference in CT values between an acrylic sphere and styroform, application of the filter caused a reduction of 4.5% in the difference in CT values. Neither reduction of the tube current nor application of the filter affected the contrast resolution of the high-contrast phantom; however, that of the low-contrast phantom deteriorated. Although improvement of the filter and evaluation of clinical images are necessary, reduction of the tube current to 20 mA and application of the aluminium filter appear to be a promising method for ultra-low-dose helical CT of the lung. (author)

  7. 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.

  8. Fragment-assisted hit investigation involving integrated HTS and fragment screening: Application to the identification of phosphodiesterase 10A (PDE10A) inhibitors.

    Science.gov (United States)

    Varnes, Jeffrey G; Geschwindner, Stefan; Holmquist, Christopher R; Forst, Janet; Wang, Xia; Dekker, Niek; Scott, Clay W; Tian, Gaochao; Wood, Michael W; Albert, Jeffrey S

    2016-01-01

    Fragment-based drug design (FBDD) relies on direct elaboration of fragment hits and typically requires high resolution structural information to guide optimization. In fragment-assisted drug discovery (FADD), fragments provide information to guide selection and design but do not serve as starting points for elaboration. We describe FADD and high-throughput screening (HTS) campaign strategies conducted in parallel against PDE10A where fragment hit co-crystallography was not available. The fragment screen led to prioritized fragment hits (IC50's ∼500μM), which were used to generate a hypothetical core scaffold. Application of this scaffold as a filter to HTS output afforded a 4μM hit, which, after preparation of a small number of analogs, was elaborated into a 16nM lead. This approach highlights the strength of FADD, as fragment methods were applied despite the absence of co-crystallographical information to efficiently identify a lead compound for further optimization. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. A Machine Learning Application Based in Random Forest for Integrating Mass Spectrometry-Based Metabolomic Data: A Simple Screening Method for Patients With Zika Virus.

    Science.gov (United States)

    Melo, Carlos Fernando Odir Rodrigues; Navarro, Luiz Claudio; de Oliveira, Diogo Noin; Guerreiro, Tatiane Melina; Lima, Estela de Oliveira; Delafiori, Jeany; Dabaja, Mohamed Ziad; Ribeiro, Marta da Silva; de Menezes, Maico; Rodrigues, Rafael Gustavo Martins; Morishita, Karen Noda; Esteves, Cibele Zanardi; de Amorim, Aline Lopes Lucas; Aoyagui, Caroline Tiemi; Parise, Pierina Lorencini; Milanez, Guilherme Paier; do Nascimento, Gabriela Mansano; Ribas Freitas, André Ricardo; Angerami, Rodrigo; Costa, Fábio Trindade Maranhão; Arns, Clarice Weis; Resende, Mariangela Ribeiro; Amaral, Eliana; Junior, Renato Passini; Ribeiro-do-Valle, Carolina C; Milanez, Helaine; Moretti, Maria Luiza; Proenca-Modena, Jose Luiz; Avila, Sandra; Rocha, Anderson; Catharino, Rodrigo Ramos

    2018-01-01

    Recent Zika outbreaks in South America, accompanied by unexpectedly severe clinical complications have brought much interest in fast and reliable screening methods for ZIKV (Zika virus) identification. Reverse-transcriptase polymerase chain reaction (RT-PCR) is currently the method of choice to detect ZIKV in biological samples. This approach, nonetheless, demands a considerable amount of time and resources such as kits and reagents that, in endemic areas, may result in a substantial financial burden over affected individuals and health services veering away from RT-PCR analysis. This study presents a powerful combination of high-resolution mass spectrometry and a machine-learning prediction model for data analysis to assess the existence of ZIKV infection across a series of patients that bear similar symptomatic conditions, but not necessarily are infected with the disease. By using mass spectrometric data that are inputted with the developed decision-making algorithm, we were able to provide a set of features that work as a "fingerprint" for this specific pathophysiological condition, even after the acute phase of infection. Since both mass spectrometry and machine learning approaches are well-established and have largely utilized tools within their respective fields, this combination of methods emerges as a distinct alternative for clinical applications, providing a diagnostic screening-faster and more accurate-with improved cost-effectiveness when compared to existing technologies.

  10. Clinical Application of Screening for GJB2 Mutations before Cochlear Implantation in a Heterogeneous Population with High Rate of Autosomal Recessive Nonsyndromic Hearing Loss

    Directory of Open Access Journals (Sweden)

    Masoud Motasaddi Zarandy

    2011-01-01

    Full Text Available Clinical application of mutation screening and its effect on the outcome of cochlear implantation is widely debated. We investigated the effect of mutations in GJB2 gene on the outcome of cochlear implantation in a population with a high rate of consanguineous marriage and autosomal recessive nonsyndromic hearing loss. Two hundred and one children with profound prelingual sensorineural hearing loss were included. Forty-six patients had 35delG in GJB2. Speech awareness thresholds (SATs and speech recognition thresholds (SRTs improved following implantation, but there was no difference in performance between patients with GJB2-related deafness versus control (all >0.10. Both groups had produced their first comprehensible words within the same period of time following implantation (2.27 months in GJB2-related deaf versus 2.62 months in controls, =0.22. Although our findings demonstrate the need to uncover unidentified genetic causes of hereditary deafness, they do not support the current policy for genetic screening before cochlear implantation, nor prove a prognostic value.

  11. Recycling wastes: its application in acoustic screens and construction materials; Residuos con necesidad de reciclado: su aplicacion en plantallas acusticas y como materiales de construccion

    Energy Technology Data Exchange (ETDEWEB)

    Santa Coloma, O.; Cortes, A.; Sanchez, J.A.

    1998-12-01

    The activities developed by man are origin of a great variety of wastes. These activities entail both the resource consumption and the generation of wastes. Both aspects are important because of the impact on the environment where man lives. If we focus on our attention on the consumption of natural resources, both economic aspects (every time the resources are more expensive) and its availability (it increases gradually the difficulty to get them). In this sense, it is very important to pro move the plans and programs necessary in order to minimize the wastes through the re utilization and recycling. Two of the options are the application of some wastes in the manufacture of acoustic screens and as construction materials. (Author)

  12. Screen dealing

    International Nuclear Information System (INIS)

    Barlow, J.W.

    1991-01-01

    The screen dealing system provides a facility whereby buyers and sellers of spot thermal coal can make bids and offers via the medium of the Reuters screen. A sale results when a market participant notifies his acceptance of a price to a central dealing desk. Use of the system is available to all genuine participants in the coal trade. This paper reports that it provides a focus for information and for the visible making of coal prices. For years screen trading has been used successfully to trade other commodities. At last coal is being traded electronically. It makes sense. It works. Users like it

  13. Facile fabrication of CdSe/CdS quantum dots and their application on the screening of colorectal cancer

    Science.gov (United States)

    Cao, Hongfeng; Dong, Quanjin; Hu, Li; Tu, Shiliang; Chai, Rui; Dai, Qiaoqiong

    2015-11-01

    In this paper, a facile aqueous route to water-soluble CdSe/CdS quantum dots (QDs) under mild conditions has been developed. The samples were characterized by means of transmission electron microscopy, energy-dispersive X-ray spectroscopy, and photoluminescence (PL) spectroscopy. The PL property of the QDs can be controlled by adjusting the reaction time. The CdSe/CdS QDs after 48-h reaction with size of 5 nm have the strongest PL intensity located at 553 nm, and the highest quantum yield of 19.9 %. The obtained QDs were applied for the colorectal cancer screening. The QDs could be conjugated with antibody of aldo-keto reductase family 1, member B10 (AKR1B10) for the detection of AKR1B10. The AKR1B10 in PBS/5 % serum solution with concentration of 1 ng/mL could be well calibrated, and the limit of detection could be lower than 0.05 ng/mL.

  14. Facile fabrication of CdSe/CdS quantum dots and their application on the screening of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Hongfeng; Dong, Quanjin, E-mail: qjdong1508@163.com [Zhejiang Provincial People’s Hospital, Department of Colorectal Surgery (China); Hu, Li [Nanjing University of Science and Technology, School of Environmental and Biological Engineering (China); Tu, Shiliang; Chai, Rui; Dai, Qiaoqiong [Zhejiang Provincial People’s Hospital, Department of Colorectal Surgery (China)

    2015-11-15

    In this paper, a facile aqueous route to water-soluble CdSe/CdS quantum dots (QDs) under mild conditions has been developed. The samples were characterized by means of transmission electron microscopy, energy-dispersive X-ray spectroscopy, and photoluminescence (PL) spectroscopy. The PL property of the QDs can be controlled by adjusting the reaction time. The CdSe/CdS QDs after 48-h reaction with size of 5 nm have the strongest PL intensity located at 553 nm, and the highest quantum yield of 19.9 %. The obtained QDs were applied for the colorectal cancer screening. The QDs could be conjugated with antibody of aldo-keto reductase family 1, member B10 (AKR1B10) for the detection of AKR1B10. The AKR1B10 in PBS/5 % serum solution with concentration of 1 ng/mL could be well calibrated, and the limit of detection could be lower than 0.05 ng/mL.

  15. STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions): application to acutely ill elderly patients and comparison with Beers' criteria.

    LENUS (Irish Health Repository)

    Gallagher, Paul

    2012-02-03

    Introduction: STOPP (Screening Tool of Older Persons\\' potentially inappropriate Prescriptions) is a new, systems-defined medicine review tool. We compared the performance of STOPP to that of established Beers\\' criteria in detecting potentially inappropriate medicines (PIMs) and related adverse drug events (ADEs) in older patients presenting for hospital admission. METHODS: we prospectively studied 715 consecutive acute admissions to a university teaching hospital. Diagnoses, reason for admission and concurrent medications were recorded. STOPP and Beers\\' criteria were applied. PIMs with clear causal connection or contribution to the principal reason for admission were determined. RESULTS: median patient age (interquartile range) was 77 (72-82) years. Median number of prescription medicines was 6 (range 0-21). STOPP identified 336 PIMs affecting 247 patients (35%), of whom one-third (n = 82) presented with an associated ADE. Beers\\' criteria identified 226 PIMs affecting 177 patients (25%), of whom 43 presented with an associated ADE. STOPP-related PIMs contributed to 11.5% of all admissions. Beers\\' criteria-related PIMs contributed to significantly fewer admissions (6%). CONCLUSION: STOPP criteria identified a significantly higher proportion of patients requiring hospitalisation as a result of PIM-related adverse events than Beers\\' criteria. This finding has significant implications for hospital geriatric practice.

  16. Spray-Deposited Large-Area Copper Nanowire Transparent Conductive Electrodes and Their Uses for Touch Screen Applications.

    Science.gov (United States)

    Chu, Hsun-Chen; Chang, Yen-Chen; Lin, Yow; Chang, Shu-Hao; Chang, Wei-Chung; Li, Guo-An; Tuan, Hsing-Yu

    2016-05-25

    Large-area conducting transparent conducting electrodes (TCEs) were prepared by a fast, scalable, and low-cost spray deposition of copper nanowire (CuNW) dispersions. Thin, long, and pure copper nanowires were obtained via the seed-mediated growth in an organic solvent-based synthesis. The mean length and diameter of nanowires are, respectively, 37.7 μm and 46 nm, corresponding to a high-mean-aspect ratio of 790. These wires were spray-deposited onto a glass substrate to form a nanowire conducting network which function as a TCE. CuNW TCEs exhibit high-transparency and high-conductivity since their relatively long lengths are advantageous in lowering in the sheet resistance. For example, a 2 × 2 cm(2) transparent nanowire electrode exhibits transmittance of T = 90% with a sheet resistance as low as 52.7 Ω sq(-1). Large-area sizes (>50 cm(2)) of CuNW TCEs were also prepared by the spray coating method and assembled as resistive touch screens that can be integrated with a variety of devices, including LED lighting array, a computer, electric motors, and audio electronic devices, showing the capability to make diverse sizes and functionalities of CuNW TCEs by the reported method.

  17. The Use of Application Blanks as Pre-Screening Devices in Employee Selection: An Assessment of Practices in Public Schools.

    Science.gov (United States)

    Bredeson, Paul V.

    1988-01-01

    Reports on a study of the use of employment application blanks as prescreening devices in public school employee selection. Findings suggest two major areas for further research. The first relates to legal compliance with Equal Opportunity Employment guidelines. The second concerns information relevancy to personnel selection. (JAM)

  18. Web-based Air Quality Screening Tool for Near-port Assessments: Example of Application in Porto, Portugal

    Science.gov (United States)

    The HARMO conference presents an opportunity to extend and further develop ORD’s collaboration with our European colleagues. This paper describes the C-PORT application in Porto, Portugal as a part of the EU project AIRSHIP designed to evaluate the air quality impacts of m...

  19. An UPLC-ESI-MS/MS Assay Using 6-Aminoquinolyl-N-Hydroxysuccinimidyl Carbamate Derivatization for Targeted Amino Acid Analysis: Application to Screening of Arabidopsis thaliana Mutants.

    Science.gov (United States)

    Salazar, Carolina; Armenta, Jenny M; Shulaev, Vladimir

    2012-07-06

    In spite of the large arsenal of methodologies developed for amino acid assessment in complex matrices, their implementation in metabolomics studies involving wide-ranging mutant screening is hampered by their lack of high-throughput, sensitivity, reproducibility, and/or wide dynamic range. In response to the challenge of developing amino acid analysis methods that satisfy the criteria required for metabolomic studies, improved reverse-phase high-performance liquid chromatography-mass spectrometry (RPHPLC-MS) methods have been recently reported for large-scale screening of metabolic phenotypes. However, these methods focus on the direct analysis of underivatized amino acids and, therefore, problems associated with insufficient retention and resolution are observed due to the hydrophilic nature of amino acids. It is well known that derivatization methods render amino acids more amenable for reverse phase chromatographic analysis by introducing highly-hydrophobic tags in their carboxylic acid or amino functional group. Therefore, an analytical platform that combines the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) pre-column derivatization method with ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) is presented in this article. For numerous reasons typical amino acid derivatization methods would be inadequate for large scale metabolic projects. However, AQC derivatization is a simple, rapid and reproducible way of obtaining stable amino acid adducts amenable for UPLC-ESI-MS/MS and the applicability of the method for high-throughput metabolomic analysis in Arabidopsis thaliana is demonstrated in this study. Overall, the major advantages offered by this amino acid analysis method include high-throughput, enhanced sensitivity and selectivity; characteristics that showcase its utility for the rapid screening of the preselected plant metabolites without compromising the quality of the metabolic data. The

  20. An UPLC-ESI-MS/MS Assay Using 6-Aminoquinolyl-N-Hydroxysuccinimidyl Carbamate Derivatization for Targeted Amino Acid Analysis: Application to Screening of Arabidopsis thaliana Mutants

    Directory of Open Access Journals (Sweden)

    Carolina Salazar

    2012-07-01

    Full Text Available In spite of the large arsenal of methodologies developed for amino acid assessment in complex matrices, their implementation in metabolomics studies involving wide-ranging mutant screening is hampered by their lack of high-throughput, sensitivity, reproducibility, and/or wide dynamic range. In response to the challenge of developing amino acid analysis methods that satisfy the criteria required for metabolomic studies, improved reverse-phase high-performance liquid chromatography-mass spectrometry (RPHPLC-MS methods have been recently reported for large-scale screening of metabolic phenotypes. However, these methods focus on the direct analysis of underivatized amino acids and, therefore, problems associated with insufficient retention and resolution are observed due to the hydrophilic nature of amino acids. It is well known that derivatization methods render amino acids more amenable for reverse phase chromatographic analysis by introducing highly-hydrophobic tags in their carboxylic acid or amino functional group. Therefore, an analytical platform that combines the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC pre-column derivatization method with ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS is presented in this article. For numerous reasons typical amino acid derivatization methods would be inadequate for large scale metabolic projects. However, AQC derivatization is a simple, rapid and reproducible way of obtaining stable amino acid adducts amenable for UPLC-ESI-MS/MS and the applicability of the method for high-throughput metabolomic analysis in Arabidopsis thaliana is demonstrated in this study. Overall, the major advantages offered by this amino acid analysis method include high-throughput, enhanced sensitivity and selectivity; characteristics that showcase its utility for the rapid screening of the preselected plant metabolites without compromising the quality of the

  1. 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.

  2. 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

  3. Airport Screening

    Science.gov (United States)

    Health Physics Society Specialists in Radiation Safety Airport Screening Fact Sheet Adopted: May 2011 Photo courtesy of Dan ... a safe level. An American National Standards Institute/Health Physics Society industry standard states that the maxi- mum ...

  4. Hypertension screening

    Science.gov (United States)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  5. Carrier Screening

    Science.gov (United States)

    ... How accurate is carrier screening? No test is perfect. In a small number of cases, test results ... in which an egg is removed from a woman’s ovary, fertilized in a laboratory with the man’s ...

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    José Augusto R. Rodrigues

    2010-01-01

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

  8. Large scale, highly conductive and patterned transparent films of silver nanowires on arbitrary substrates and their application in touch screens

    International Nuclear Information System (INIS)

    Madaria, Anuj R; Kumar, Akshay; Zhou Chongwu

    2011-01-01

    The application of silver nanowire films as transparent conductive electrodes has shown promising results recently. In this paper, we demonstrate the application of a simple spray coating technique to obtain large scale, highly uniform and conductive silver nanowire films on arbitrary substrates. We also integrated a polydimethylsiloxane (PDMS)-assisted contact transfer technique with spray coating, which allowed us to obtain large scale high quality patterned films of silver nanowires. The transparency and conductivity of the films was controlled by the volume of the dispersion used in spraying and the substrate area. We note that the optoelectrical property, σ DC /σ Op , for various films fabricated was in the range 75-350, which is extremely high for transparent thin film compared to other candidate alternatives to doped metal oxide film. Using this method, we obtain silver nanowire films on a flexible polyethylene terephthalate (PET) substrate with a transparency of 85% and sheet resistance of 33 Ω/sq, which is comparable to that of tin-doped indium oxide (ITO) on flexible substrates. In-depth analysis of the film shows a high performance using another commonly used figure-of-merit, Φ TE . Also, Ag nanowire film/PET shows good mechanical flexibility and the application of such a conductive silver nanowire film as an electrode in a touch panel has been demonstrated.

  9. Large scale, highly conductive and patterned transparent films of silver nanowires on arbitrary substrates and their application in touch screens.

    Science.gov (United States)

    Madaria, Anuj R; Kumar, Akshay; Zhou, Chongwu

    2011-06-17

    The application of silver nanowire films as transparent conductive electrodes has shown promising results recently. In this paper, we demonstrate the application of a simple spray coating technique to obtain large scale, highly uniform and conductive silver nanowire films on arbitrary substrates. We also integrated a polydimethylsiloxane (PDMS)-assisted contact transfer technique with spray coating, which allowed us to obtain large scale high quality patterned films of silver nanowires. The transparency and conductivity of the films was controlled by the volume of the dispersion used in spraying and the substrate area. We note that the optoelectrical property, σ(DC)/σ(Op), for various films fabricated was in the range 75-350, which is extremely high for transparent thin film compared to other candidate alternatives to doped metal oxide film. Using this method, we obtain silver nanowire films on a flexible polyethylene terephthalate (PET) substrate with a transparency of 85% and sheet resistance of 33 Ω/sq, which is comparable to that of tin-doped indium oxide (ITO) on flexible substrates. In-depth analysis of the film shows a high performance using another commonly used figure-of-merit, Φ(TE). Also, Ag nanowire film/PET shows good mechanical flexibility and the application of such a conductive silver nanowire film as an electrode in a touch panel has been demonstrated.

  10. 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)....

  11. 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)...

  12. Microcystin-LR nanobody screening from an alpaca phage display nanobody library and its expression and application.

    Science.gov (United States)

    Xu, Chongxin; Yang, Ying; Liu, Liwen; Li, Jianhong; Liu, Xiaoqin; Zhang, Xiao; Liu, Yuan; Zhang, Cunzheng; Liu, Xianjin

    2018-04-30

    Microcystin-LR (MC-LR) is a type of biotoxin that pollutes the ecological environment and food. The study aimed to obtain new nanobodies from phage nanobody library for determination of MC-LR. The toxin was conjugated to keyhole limpet haemocyanin (KLH) and bovine serum albumin (BSA), respectively, then the conjugates were used as coated antigens for enrichment (coated MC-LR-KLH) and screening (coated MC-LR-BSA) of MC-LR phage nanobodies from an alpaca phage display nanobody library. The antigen-specific phage particles were enriched effectively with four rounds of biopanning. At the last round of enrichment, total 20 positive monoclonal phage nanobodies were obtained from the library, which were analyzed after monoclonal phage enzyme linked immunosorbent assay (ELISA), colony PCR and DNA sequencing. The most three positive nanobody genes, ANAb12, ANAb9 and ANAb7 were cloned into pET26b vector, then the nanobodies were expressed in Escherichia coli BL21 respectively. After being purified, the molecular weight (M.W.) of all nanobodies were approximate 15kDa with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The purified nanobodies, ANAb12, ANAb9 and ANAb7 were used to establish the indirect competitive ELISA (IC-ELISA) for MC-LR, and their half-maximum inhibition concentrations (IC 50 ) were 0.87, 1.17 and 1.47μg/L, their detection limits (IC 10 ) were 0.06, 0.08 and 0.12μg/L, respectively. All of them showed strong cross-reactivity (CRs) of 82.7-116.9% for MC-RR, MC-YR and MC-WR, and weak CRs of less than 4.56% for MC-LW, less than 0.1% for MC-LY and MC-LF. It was found that all the IC-ELISAs for MC-LR spiked in tap water samples detection were with good accuracy, stability and repeatability, their recoveries were 84.0-106.5%, coefficient of variations (CVs) were 3.4-10.6%. These results showed that IC-ELISA based on the nanobodies from the alpaca phage display antibody library were promising for high sensitive determination of multiple

  13. Nutritional screening tools application in a general hospital: a comparative study Aplicação de instrumentos de triagem nutricional em hospital geral: um estudo comparativo

    Directory of Open Access Journals (Sweden)

    Janaína Damasceno Bezerra

    2012-05-01

    Full Text Available Introduction: There are many nutritional screening tools and it becomes difficult to choose which one is the best to be used in clinical nutrition practice. Objective: To compare five nutritional screening tools (MST, NRS-2002, MUST, MNA and MNA-SF in adults and elderly hospitalized. Materials and Methods: A cross-sectional study, with the application of nutritional screening tools in adult and elderly patients in the first 48 hours of hospitalization was performed. Nutritional risk occurrence between adult and elderly patients was compared. Statistical analyses were performed using descriptive data and a non-parametric test (Man Whitney. Results: We evaluated 77 patients, 51 (66.2% adults and 26 (33.8% elderly, aged 53.6 (standard deviation of 17.9 years, with female predominance (53.2%. The main reasons for hospitalization were neoplasia and nephrolithotripsy. Overall, one quarter of patients was at nutritional risk. Nutritional risk in adults was detected with similarity by MUST and MST. However it was underestimated by NRS-2002. The MNA and MNA-SF, exclusively for the elderly, also had similar result to detect nutritional risk. In relation to the time of application, the MNA was the instrument with longer application time. Conclusion: Considering the higher detection of patients with nutritional risk, the easiness and the lower application time, we suggest, respectively, MUST and MNA-SF to be used in adult and elderly patients admitted in this hospital.Introdução: Com inúmeros instrumentos de triagem nutricional existentes, é difícil eleger o mais adequado para os protocolos de nutrição hospitalar. Objetivo: Comparar cinco instrumentos de triagem nutricional (MST, NRS-2002, MUST, MNA e MNA-SF em adultos e idosos hospitalizados. Materiais e Métodos: Nesse estudo transversal, cinco instrumentos de triagem nutricional foram aplicados aos pacientes nas primeiras 48 horas de internação hospitalar. A ocorrência de risco nutricional

  14. Identification of neuropathic pain in patients with neck/upper limb pain: application of a grading system and screening tools.

    Science.gov (United States)

    Tampin, Brigitte; Briffa, Noelle Kathryn; Goucke, Roger; Slater, Helen

    2013-12-01

    The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain has proposed a grading system for the presence of neuropathic pain (NeP) using the following categories: no NeP, possible, probable, or definite NeP. To further evaluate this system, we investigated patients with neck/upper limb pain with a suspected nerve lesion, to explore: (i) the clinical application of this grading system; (ii) the suitability of 2 NeP questionnaires (Leeds Assessment of Neuropathic Symptoms and Signs pain scale [LANSS] and the painDETECT questionnaire [PD-Q]) in identifying NeP in this patient cohort; and (iii) the level of agreement in identifying NeP between the NeuPSIG classification system and 2 NeP questionnaires. Patients (n = 152; age 52 ± 12 years; 53% male) completed the PD-Q and LANSS questionnaire and underwent a comprehensive clinical examination. The NeuPSIG grading system proved feasible for application in this patient cohort, although it required considerable time and expertise. Both questionnaires failed to identify a large number of patients with clinically classified definite NeP (LANSS sensitivity 22%, specificity 88%; PD-Q sensitivity 64%, specificity 62%). These lowered sensitivity scores contrast with those from the original PD-Q and LANSS validation studies and may reflect differences in the clinical characteristics of the study populations. The diagnostic accuracy of LANSS and PD-Q for the identification of NeP in patients with neck/upper limb pain appears limited. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  15. Luminescent screens

    International Nuclear Information System (INIS)

    Lu, C.-I.

    1982-01-01

    Luminescent screens which are useful for such purposes as intensifying screens for radiographs are comprised of a support bearing a layer of finely divided particles of a phosphor dispersed in a cross-linked polymeric matrix formed by heat-curing of a coating composition comprising an unsaturated cross-linkable polymer, a polymerizable acrylic monomer, a thermoplastic polyurethane elastomer, and a heat-activatable polymerization initiator. The phosphor layer includes voids formed by evaporation of an evaporable component which is present in the coating composition from which such layer is formed. (author)

  16. The Impact of Patient Education with a Smartphone Application on the Quality of Bowel Preparation for Screening Colonoscopy.

    Science.gov (United States)

    Cho, JeongHyeon; Lee, SeungHee; Shin, Jung A; Kim, Jeong Ho; Lee, Hong Sub

    2017-09-01

    Few studies have evaluated the use of a smartphone application (app) for educating people undergoing colonoscopy and optimizing bowel preparation. Therefore, this study was designed to develop a smartphone app for people to use as a preparation guide and to evaluate the efficacy of this app when used prior to colonoscopy. In total, 142 patients (male:female=84:58, mean age=43.5±9.3 years), who were scheduled to undergo a colonoscopy at Myongji Hospital, were enrolled in this study. Seventy-one patients were asked to use a smartphone app that we had recently developed to prepare for the colonoscopy, while the 71 patients of the sex and age-matched control group were educated via written and verbal instructions. The quality of bowel cleansing, evaluated using the Boston Bowel Preparation Scale, was significantly higher in the smartphone app group than in the control group (7.70±1.1 vs. 7.24±0.8, respectively, p =0.007 by t -test). No significant differences were found between the two groups regarding work-up time and the number of patients with polyps. In this study, targeting young adults (≤50 years), the bowel preparation achieved by patients using the smartphone app showed significantly better quality than that of the control group.

  17. Application of DNA Hybridization Biosensor as a Screening Method for the Detection of Genetically Modified Food Components

    Directory of Open Access Journals (Sweden)

    Marian Filipiak

    2008-03-01

    Full Text Available An electrochemical biosensor for the detection of genetically modified food components is presented. The biosensor was based on 21-mer single-stranded oligonucleotide (ssDNA probe specific to either 35S promoter or nos terminator, which are frequently present in transgenic DNA cassettes. ssDNA probe was covalently attached by 5’-phosphate end to amino group of cysteamine self-assembled monolayer (SAM on gold electrode surface with the use of activating reagents – water soluble 1-ethyl-3(3’- dimethylaminopropyl-carbodiimide (EDC and N-hydroxy-sulfosuccinimide (NHS. The hybridization reaction on the electrode surface was detected via methylene blue (MB presenting higher affinity to ssDNA probe than to DNA duplex. The electrode modification procedure was optimized using 19-mer oligoG and oligoC nucleotides. The biosensor enabled distinction between DNA samples isolated from soybean RoundupReady® (RR soybean and non-genetically modified soybean. The frequent introduction of investigated DNA sequences in other genetically modified organisms (GMOs give a broad perspectives for analytical application of the biosensor.

  18. Alcohol Use Screening

    Science.gov (United States)

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

  19. 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.

  20. 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.

  1. Validation of projective mapping as potential sensory screening tool for application by the honeybush herbal tea industry.

    Science.gov (United States)

    Moelich, Erika Ilette; Muller, Magdalena; Joubert, Elizabeth; Næs, Tormod; Kidd, Martin

    2017-09-01

    Honeybush herbal tea is produced from the endemic South African Cyclopia species. Plant material subjected to a high-temperature oxidation step ("fermentation") forms the bulk of production. Production lags behind demand forcing tea merchants to use blends of available material to supply local and international markets. The distinct differences in the sensory profiles of the herbal tea produced from the different Cyclopia species require that special care is given to blending to ensure a consistent, high quality product. Although conventional descriptive sensory analysis (DSA) is highly effective in providing a detailed sensory profile of herbal tea infusions, industry requires a method that is more time- and cost-effective. Recent advances in sensory science have led to the development of rapid profiling methodologies. The question is whether projective mapping can successfully be used for the sensory characterisation of herbal tea infusions. Trained assessors performed global and partial projective mapping to determine the validity of this technique for the sensory characterisation of infusions of five Cyclopia species. Similar product configurations were obtained when comparing results of DSA and global and partial projective mapping. Comparison of replicate sessions showed RV coefficients >0.8. A similarity index, based on multifactor analysis, was calculated to determine assessor repeatability. Global projective mapping, demonstrated to be a valid method for providing a broad sensory characterisation of Cyclopia species, is thus suitable as a rapid quality control method of honeybush infusions. Its application by the honeybush industry could improve the consistency of the sensory profile of blended products. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Hearing Screening

    Science.gov (United States)

    Johnson-Curiskis, Nanette

    2012-01-01

    Hearing levels are threatened by modern life--headsets for music, rock concerts, traffic noises, etc. It is crucial we know our hearing levels so that we can draw attention to potential problems. This exercise requires that students receive a hearing screening for their benefit as well as for making the connection of hearing to listening.

  3. Vision Screening

    Science.gov (United States)

    ... an efficient and cost-effective method to identify children with visual impairment or eye conditions that are likely to lead ... main goal of vision screening is to identify children who have or are at ... visual impairment unless treated in early childhood. Other problems that ...

  4. Development of a Clinical Forecasting Model to Predict Comorbid Depression Among Diabetes Patients and an Application in Depression Screening Policy Making

    OpenAIRE

    Jin, Haomiao; Wu, Shinyi; Di Capua, Paul

    2015-01-01

    Introduction Depression is a common but often undiagnosed comorbid condition of people with diabetes. Mass screening can detect undiagnosed depression but may require significant resources and time. The objectives of this study were 1) to develop a clinical forecasting model that predicts comorbid depression among patients with diabetes and 2) to evaluate a model-based screening policy that saves resources and time by screening only patients considered as depressed by the clinical forecasting...

  5. Application of support vector machine to three-dimensional shape-based virtual screening using comprehensive three-dimensional molecular shape overlay with known inhibitors.

    Science.gov (United States)

    Sato, Tomohiro; Yuki, Hitomi; Takaya, Daisuke; Sasaki, Shunta; Tanaka, Akiko; Honma, Teruki

    2012-04-23

    In this study, machine learning using support vector machine was combined with three-dimensional (3D) molecular shape overlay, to improve the screening efficiency. Since the 3D molecular shape overlay does not use fingerprints or descriptors to compare two compounds, unlike 2D similarity methods, the application of machine learning to a 3D shape-based method has not been extensively investigated. The 3D similarity profile of a compound is defined as the array of 3D shape similarities with multiple known active compounds of the target protein and is used as the explanatory variable of support vector machine. As the measures of 3D shape similarity for our new prediction models, the prediction performances of the 3D shape similarity metrics implemented in ROCS, such as ShapeTanimoto and ScaledColor, were validated, using the known inhibitors of 15 target proteins derived from the ChEMBL database. The learning models based on the 3D similarity profiles stably outperformed the original ROCS when more than 10 known inhibitors were available as the queries. The results demonstrated the advantages of combining machine learning with the 3D similarity profile to process the 3D shape information of plural active compounds.

  6. Application of a diagnostic methodology by quantification of 26:0 lysophosphatidylcholine in dried blood spots for Japanese newborn screening of X-linked adrenoleukodystrophy

    Directory of Open Access Journals (Sweden)

    Chen Wu

    2017-09-01

    Full Text Available X-linked adrenoleukodystrophy (X-ALD is a rare inherited metabolic disease that results in the accumulation of very long chain fatty acids (VLCFA in plasma and all tissues. Recent studies regarding cerebral X-ALD (CALD treatment emphasize the importance of its early diagnosis. 26:0 lysophosphatidylcholine (LysoPC is a sensitive biomarker for newborn screening of X-ALD, while its application for Japanese DBS is unclear. Therefore, we evaluated the feasibility of 20:0 LysoPC and 24:0 LysoPC along with 26:0 LysoPC for diagnosing X-ALD in a cohort of newborns (n = 604, healthy adults (n = 50 and patients (n = 4. Results indicated that 26:0 LysoPC had strong significance for discrimination of patients by the amounts of 2.0 to 4.0 and 0.1 to 1.9 pmol/punch for patients and newborns/healthy adults, respectively. Based on these values, we recommend that further diagnostic confirmation is essential if the amount of 26:0 LysoPC in DBS is above 1.7 pmol/punch.

  7. A Machine Learning Application Based in Random Forest for Integrating Mass Spectrometry-Based Metabolomic Data: A Simple Screening Method for Patients With Zika Virus

    Directory of Open Access Journals (Sweden)

    Carlos Fernando Odir Rodrigues Melo

    2018-04-01

    Full Text Available Recent Zika outbreaks in South America, accompanied by unexpectedly severe clinical complications have brought much interest in fast and reliable screening methods for ZIKV (Zika virus identification. Reverse-transcriptase polymerase chain reaction (RT-PCR is currently the method of choice to detect ZIKV in biological samples. This approach, nonetheless, demands a considerable amount of time and resources such as kits and reagents that, in endemic areas, may result in a substantial financial burden over affected individuals and health services veering away from RT-PCR analysis. This study presents a powerful combination of high-resolution mass spectrometry and a machine-learning prediction model for data analysis to assess the existence of ZIKV infection across a series of patients that bear similar symptomatic conditions, but not necessarily are infected with the disease. By using mass spectrometric data that are inputted with the developed decision-making algorithm, we were able to provide a set of features that work as a “fingerprint” for this specific pathophysiological condition, even after the acute phase of infection. Since both mass spectrometry and machine learning approaches are well-established and have largely utilized tools within their respective fields, this combination of methods emerges as a distinct alternative for clinical applications, providing a diagnostic screening—faster and more accurate—with improved cost-effectiveness when compared to existing technologies.

  8. Kinetic comparison of tissue non-specific and placental human alkaline phosphatases expressed in baculovirus infected cells: application to screening for Down's syndrome.

    Science.gov (United States)

    Denier, Colette C; Brisson-Lougarre, Andrée A; Biasini, Ghislaine G; Grozdea, Jean J; Fournier, Didier D

    2002-01-01

    In humans, there are four alkaline phosphatases, and each form exhibits a characteristic pattern of tissue distribution. The availability of an easy method to reveal their activity has resulted in large amount of data reporting correlations between variations in activity and illnesses. For example, alkaline phosphatase from neutrophils of mothers pregnant with a trisomy 21 fetus (Down's syndrome) displays significant differences both in its biochemical and immunological properties, and in its affinity for some specific inhibitors. To analyse these differences, the biochemical characteristics of two isozymes (non specific and placental alkaline phosphatases) were expressed in baculovirus infected cells. Comparative analysis of the two proteins allowed us to estimate the kinetic constants of denaturation and sensitivity to two inhibitors (L-p-bromotetramisole and thiophosphate), allowing better discrimination between the two enzymes. These parameters were then used to estimate the ratio of the two isoenzymes in neutrophils of pregnant mothers with or without a trisomy 21 fetus. It appeared that the placental isozyme represented 13% of the total activity of neutrophils of non pregnant women. This proportion did not significantly increase with normal pregnancy. By contrast, in pregnancies with trisomy 21 fetus, the proportion reached 60-80% of activity. Over-expression of the placental isozyme compared with the tissue-nonspecific form in neutrophils of mother with a trisomy 21 fetus may explain why the characteristics of the alkaline phosphatase in these cells is different from normal. Application of this knowledge could improve the potential of using alkaline phosphatase measurements to screen for Down's syndrome.

  9. Data Mining Approaches for Genomic Biomarker Development: Applications Using Drug Screening Data from the Cancer Genome Project and the Cancer Cell Line Encyclopedia.

    Directory of Open Access Journals (Sweden)

    David G Covell

    Full Text Available Developing reliable biomarkers of tumor cell drug sensitivity and resistance can guide hypothesis-driven basic science research and influence pre-therapy clinical decisions. A popular strategy for developing biomarkers uses characterizations of human tumor samples against a range of cancer drug responses that correlate with genomic change; developed largely from the efforts of the Cancer Cell Line Encyclopedia (CCLE and Sanger Cancer Genome Project (CGP. The purpose of this study is to provide an independent analysis of this data that aims to vet existing and add novel perspectives to biomarker discoveries and applications. Existing and alternative data mining and statistical methods will be used to a evaluate drug responses of compounds with similar mechanism of action (MOA, b examine measures of gene expression (GE, copy number (CN and mutation status (MUT biomarkers, combined with gene set enrichment analysis (GSEA, for hypothesizing biological processes important for drug response, c conduct global comparisons of GE, CN and MUT as biomarkers across all drugs screened in the CGP dataset, and d assess the positive predictive power of CGP-derived GE biomarkers as predictors of drug response in CCLE tumor cells. The perspectives derived from individual and global examinations of GEs, MUTs and CNs confirm existing and reveal unique and shared roles for these biomarkers in tumor cell drug sensitivity and resistance. Applications of CGP-derived genomic biomarkers to predict the drug response of CCLE tumor cells finds a highly significant ROC, with a positive predictive power of 0.78. The results of this study expand the available data mining and analysis methods for genomic biomarker development and provide additional support for using biomarkers to guide hypothesis-driven basic science research and pre-therapy clinical decisions.

  10. Vision Screening

    Science.gov (United States)

    1993-01-01

    The Visi Screen OSS-C, marketed by Vision Research Corporation, incorporates image processing technology originally developed by Marshall Space Flight Center. Its advantage in eye screening is speed. Because it requires no response from a subject, it can be used to detect eye problems in very young children. An electronic flash from a 35 millimeter camera sends light into a child's eyes, which is reflected back to the camera lens. The photorefractor then analyzes the retinal reflexes generated and produces an image of the child's eyes, which enables a trained observer to identify any defects. The device is used by pediatricians, day care centers and civic organizations that concentrate on children with special needs.

  11. Mathematical Models of the Sinusoidal Screen Family

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. Perturbing dissimilar biomolecular targets from natural product scaffolds and focused chemical decoration

    DEFF Research Database (Denmark)

    Nielsen, John; Tung, Truong Thanh; Tim, Holm Jakobsen

    agents. On first attempt, by screening natural product sources we have successfully discovered that curcuminoids as potent inhibitors of p-type ATPases from diverse kingdoms of life including Pma1. On other attempt, the fungal metabolite fusaric acid was reported to reduce stomatal conductance in banana...

  14. 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...

  15. 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)

  16. Application of direct agglutination test (DAT) and fast agglutination screening test (FAST) for sero-diagnosis of visceral leishmaniasis in endemic area of Minas Gerais, Brazil

    NARCIS (Netherlands)

    Silva, Eduardo S.; Schoone, Gerard J.; Gontijo, Celia M. F.; Brazil, Reginaldo P.; Pacheco, Raquel S.; Schallig, Henk D. F. H.

    2005-01-01

    The direct agglutination test (DAT) has proved to be a very important sero-diagnostic tool combining high levels of intrinsic validity and ease of performance. Otherwise, fast agglutination screening test (FAST) utilises only one serum dilution making the test very suitable for the screening of

  17. Structural Characterization and Absolute Luminescence Efficiency Evaluation of Gd2O2S High Packing Density Ceramic Screens Doped with Tb3+ and Eu3+ for further Applications in Radiology

    Science.gov (United States)

    Dezi, Anna; Monachesi, Elenasophie; D'Ignazio, Michela; Scalise, Lorenzo; Montalto, Luigi; Paone, Nicola; Rinaldi, Daniele; Mengucci, Paolo; Loudos, George; Bakas, Athanasios; Michail, Christos; Valais, Ioannis; Fountzoula, Christine; Fountos, George; David, Stratos

    2017-11-01

    Rare earth activators are impurities added in the phosphor material to enhance probability of visible photon emission during the luminescence process. The main activators employed are rare earth trivalent ions such as Ce+3, Tb+3, Pr3+ and Eu+3. In this work, four terbium-activated Gd2O2S (GOS) powder screens with different thicknesses (1049 mg/cm2, 425.41 mg/cm2, 313 mg/cm2 and 187.36 mg/cm2) and one europium-activated GOS powder screen (232.18 mg/cm2) were studied to investigate possible applications for general radiology detectors. Results presented relevant differences in crystallinity between the GOS:Tb doped screens and GOS:Eu screens in respect to the dopant agent present. The AE (Absolute efficiency) was found to rise (i) with the increase of the X-ray tube voltage with the highest peaking at 110kVp and (ii) with the decrease of the thickness among the four GOS:Tb. Comparing similar thickness values, the europium-activated powder screen showed lower AE than the corresponding terbium-activated.

  18. 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 t