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Sample records for high-throughput quantum chemistry

  1. High-throughput quantum chemistry and virtual screening for OLED material components

    Science.gov (United States)

    Halls, Mathew D.; Giesen, David J.; Hughes, Thomas F.; Goldberg, Alexander; Cao, Yixiang

    2013-09-01

    Computational structure enumeration, analysis using an automated simulation workflow and filtering of large chemical structure libraries to identify lead systems, has become a central paradigm in drug discovery research. Transferring this paradigm to challenges in materials science is now possible due to advances in the speed of computational resources and the efficiency and stability of chemical simulation packages. State-of-the-art software tools that have been developed for drug discovery can be applied to efficiently explore the chemical design space to identify solutions for problems such as organic light-emitting diode material components. In this work, virtual screening for OLED materials based on intrinsic quantum mechanical properties is illustrated. Also, a new approach to more reliably identify candidate systems is introduced that is based on the chemical reaction energetics of defect pathways for OLED materials.

  2. Quantum chemistry

    CERN Document Server

    Lowe, John P

    1993-01-01

    Praised for its appealing writing style and clear pedagogy, Lowe's Quantum Chemistry is now available in its Second Edition as a text for senior undergraduate- and graduate-level chemistry students. The book assumes little mathematical or physical sophistication and emphasizes an understanding of the techniques and results of quantum chemistry, thus enabling students to comprehend much of the current chemical literature in which quantum chemical methods or concepts are used as tools. The book begins with a six-chapter introduction of standard one-dimensional systems, the hydrogen atom,

  3. Life in the fast lane: high-throughput chemistry for lead generation and optimisation.

    Science.gov (United States)

    Hunter, D

    2001-01-01

    The pharmaceutical industry has come under increasing pressure due to regulatory restrictions on the marketing and pricing of drugs, competition, and the escalating costs of developing new drugs. These forces can be addressed by the identification of novel targets, reductions in the development time of new drugs, and increased productivity. Emphasis has been placed on identifying and validating new targets and on lead generation: the response from industry has been very evident in genomics and high throughput screening, where new technologies have been applied, usually coupled with a high degree of automation. The combination of numerous new potential biological targets and the ability to screen large numbers of compounds against many of these targets has generated the need for large diverse compound collections. To address this requirement, high-throughput chemistry has become an integral part of the drug discovery process. Copyright 2002 Wiley-Liss, Inc.

  4. High Throughput Facility

    Data.gov (United States)

    Federal Laboratory Consortium — Argonne?s high throughput facility provides highly automated and parallel approaches to material and materials chemistry development. The facility allows scientists...

  5. Turbocharged molecular discovery of OLED emitters: from high-throughput quantum simulation to highly efficient TADF devices

    Science.gov (United States)

    Gómez-Bombarelli, Rafael; Aguilera-Iparraguirre, Jorge; Hirzel, Timothy D.; Ha, Dong-Gwang; Einzinger, Markus; Wu, Tony; Baldo, Marc A.; Aspuru-Guzik, Alán.

    2016-09-01

    Discovering new OLED emitters requires many experiments to synthesize candidates and test performance in devices. Large scale computer simulation can greatly speed this search process but the problem remains challenging enough that brute force application of massive computing power is not enough to successfully identify novel structures. We report a successful High Throughput Virtual Screening study that leveraged a range of methods to optimize the search process. The generation of candidate structures was constrained to contain combinatorial explosion. Simulations were tuned to the specific problem and calibrated with experimental results. Experimentalists and theorists actively collaborated such that experimental feedback was regularly utilized to update and shape the computational search. Supervised machine learning methods prioritized candidate structures prior to quantum chemistry simulation to prevent wasting compute on likely poor performers. With this combination of techniques, each multiplying the strength of the search, this effort managed to navigate an area of molecular space and identify hundreds of promising OLED candidate structures. An experimentally validated selection of this set shows emitters with external quantum efficiencies as high as 22%.

  6. High-throughput experimentation in synthetic polymer chemistry: From RAFT and anionic polymerizations to process development

    NARCIS (Netherlands)

    Guerrero-Sanchez, C.A.; Paulus, R.M.; Fijten, M.W.M.; Mar, de la M.J.; Hoogenboom, R.; Schubert, U.S.

    2006-01-01

    The application of combinatorial and high-throughput approaches in polymer research is described. An overview of the utilized synthesis robots is given, including different parallel synthesizers and a process development robot. In addition, the application of the parallel synthesis robots to

  7. New high-throughput material-exploration system based on combinatorial chemistry and electrostatic atomization

    International Nuclear Information System (INIS)

    Fujimoto, K.; Takahashi, H.; Ito, S.; Inoue, S.; Watanabe, M.

    2006-01-01

    As a tool to facilitate future material explorations, our group has developed a new combinatorial system for the high-throughput preparation of compounds made up of more than three components. The system works in two steps: the atomization of a liquid by a high electric field followed by deposition to a grounded substrate. The combinatorial system based on this method has plural syringe pumps. The each starting materials are fed through the syringe pumps into a manifold, thoroughly mixed as they pass through the manifold, and atomized from the tip of a stainless steel nozzle onto a grounded substrate

  8. Enzyme-Initiated Quinone-Chitosan Conjugation Chemistry: Toward A General in Situ Strategy for High-Throughput Photoelectrochemical Enzymatic Bioanalysis.

    Science.gov (United States)

    Wang, Guang-Li; Yuan, Fang; Gu, Tiantian; Dong, Yuming; Wang, Qian; Zhao, Wei-Wei

    2018-02-06

    Herein we report a general and novel strategy for high-throughput photoelectrochemical (PEC) enzymatic bioanalysis on the basis of enzyme-initiated quinone-chitosan conjugation chemistry (QCCC). Specifically, the strategy was illustrated by using a model quinones-generating oxidase of tyrosinase (Tyr) to catalytically produce 1,2-bezoquinone or its derivative, which can easily and selectively be conjugated onto the surface of the chitosan deposited PbS/NiO/FTO photocathode via the QCCC. Upon illumination, the covalently attached quinones could act as electron acceptors of PbS quantum dots (QDs), improving the photocurrent generation and thus allowing the elegant probing of Tyr activity. Enzyme cascades, such as alkaline phosphatase (ALP)/Tyr and β-galactosidase (Gal)/Tyr, were further introduced into the system for the successful probing of the corresponding targets. This work features not only the first use of QCCC in PEC bioanalysis but also the separation of enzymatic reaction from the photoelectrode as well as the direct signal recording in a split-type protocol, which enables quite convenient and high-throughput detection as compared to previous formats. More importantly, by using numerous other oxidoreductases that involve quinones as reactants/products, this protocol could serve as a common basis for the development of a new class of QCCC-based PEC enzymatic bioanalysis and further extended for general enzyme-labeled PEC bioanalysis of versatile targets.

  9. High-throughput density functional calculations to optimize properties and interfacial chemistry of piezoelectric materials

    Science.gov (United States)

    Barr, Jordan A.; Lin, Fang-Yin; Ashton, Michael; Hennig, Richard G.; Sinnott, Susan B.

    2018-02-01

    High-throughput density functional theory calculations are conducted to search through 1572 A B O3 compounds to find a potential replacement material for lead zirconate titanate (PZT) that exhibits the same excellent piezoelectric properties as PZT and lacks both its use of the toxic element lead (Pb) and the formation of secondary alloy phases with platinum (Pt) electrodes. The first screening criterion employed a search through the Materials Project database to find A -B combinations that do not form ternary compounds with Pt. The second screening criterion aimed to eliminate potential candidates through first-principles calculations of their electronic structure, in which compounds with a band gap of 0.25 eV or higher were retained. Third, thermodynamic stability calculations were used to compare the candidates in a Pt environment to compounds already calculated to be stable within the Materials Project. Formation energies below or equal to 100 meV/atom were considered to be thermodynamically stable. The fourth screening criterion employed lattice misfit to identify those candidate perovskites that have low misfit with the Pt electrode and high misfit of potential secondary phases that can be formed when Pt alloys with the different A and B components. To aid in the final analysis, dynamic stability calculations were used to determine those perovskites that have dynamic instabilities that favor the ferroelectric distortion. Analysis of the data finds three perovskites warranting further investigation: CsNb O3 , RbNb O3 , and CsTa O3 .

  10. High-Throughput Synthetic Chemistry Enabled by Organic Solvent Disintegrating Tablet.

    Science.gov (United States)

    Li, Tingting; Xu, Lei; Xing, Yanjun; Xu, Bo

    2017-01-17

    Synthetic chemistry remains a time- and labor-intensive process of inherent hazardous nature. Our organic solvent disintegrating tablet (O-Tab) technology has shown potential to make industrial/synthetic chemistry more efficient. As is the case with pharmaceutical tablets, our reagent-containing O-Tabs are mechanically strong, but disintegrate rapidly when in contact with reaction media (organic solvents). For O-Tabs containing sensitive chemicals, they can be further coated to insulate them from air and moisture. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Principles of quantum chemistry

    CERN Document Server

    George, David V

    2013-01-01

    Principles of Quantum Chemistry focuses on the application of quantum mechanics in physical models and experiments of chemical systems.This book describes chemical bonding and its two specific problems - bonding in complexes and in conjugated organic molecules. The very basic theory of spectroscopy is also considered. Other topics include the early development of quantum theory; particle-in-a-box; general formulation of the theory of quantum mechanics; and treatment of angular momentum in quantum mechanics. The examples of solutions of Schroedinger equations; approximation methods in quantum c

  12. Advances in quantum chemistry

    CERN Document Server

    Sabin, John R

    2013-01-01

    Advances in Quantum Chemistry presents surveys of current topics in this rapidly developing field that has emerged at the cross section of the historically established areas of mathematics, physics, chemistry, and biology. It features detailed reviews written by leading international researchers. This volume focuses on the theory of heavy ion physics in medicine.Advances in Quantum Chemistry presents surveys of current topics in this rapidly developing field that has emerged at the cross section of the historically established areas of mathematics, physics, chemistry, and biology. It features

  13. A microliter-scale high-throughput screening system with quantum-dot nanoprobes for amyloid-β aggregation inhibitors.

    Directory of Open Access Journals (Sweden)

    Yukako Ishigaki

    Full Text Available The aggregation of amyloid β protein (Aβ is a key step in the pathogenesis of Alzheimer's disease (AD, and therefore inhibitory substances for Aβ aggregation may have preventive and/or therapeutic potential for AD. Here we report a novel microliter-scale high-throughput screening system for Aβ aggregation inhibitors based on fluorescence microscopy-imaging technology with quantum-dot Nanoprobes. This screening system could be analyzed with a 5-µl sample volume when a 1536-well plate was used, and the inhibitory activity could be estimated as half-maximal effective concentrations (EC50. We attempted to comprehensively screen Aβ aggregation inhibitors from 52 spices using this system to assess whether this novel screening system is actually useful for screening inhibitors. Screening results indicate that approximately 90% of the ethanolic extracts from the spices showed inhibitory activity for Aβ aggregation. Interestingly, spices belonging to the Lamiaceae, the mint family, showed significantly higher activity than the average of tested spices. Furthermore, we tried to isolate the main inhibitory compound from Saturejahortensis, summer savory, a member of the Lamiaceae, using this system, and revealed that the main active compound was rosmarinic acid. These results demonstrate that this novel microliter-scale high-throughput screening system could be applied to the actual screening of Aβ aggregation inhibitors. Since this system can analyze at a microscopic scale, it is likely that further minimization of the system would easily be possible such as protein microarray technology.

  14. Development of combinatorial chemistry methods for coatings: high-throughput adhesion evaluation and scale-up of combinatorial leads.

    Science.gov (United States)

    Potyrailo, Radislav A; Chisholm, Bret J; Morris, William G; Cawse, James N; Flanagan, William P; Hassib, Lamyaa; Molaison, Chris A; Ezbiansky, Karin; Medford, George; Reitz, Hariklia

    2003-01-01

    Coupling of combinatorial chemistry methods with high-throughput (HT) performance testing and measurements of resulting properties has provided a powerful set of tools for the 10-fold accelerated discovery of new high-performance coating materials for automotive applications. Our approach replaces labor-intensive steps with automated systems for evaluation of adhesion of 8 x 6 arrays of coating elements that are discretely deposited on a single 9 x 12 cm plastic substrate. Performance of coatings is evaluated with respect to their resistance to adhesion loss, because this parameter is one of the primary considerations in end-use automotive applications. Our HT adhesion evaluation provides previously unavailable capabilities of high speed and reproducibility of testing by using a robotic automation, an expanded range of types of tested coatings by using the coating tagging strategy, and an improved quantitation by using high signal-to-noise automatic imaging. Upon testing, the coatings undergo changes that are impossible to quantitatively predict using existing knowledge. Using our HT methodology, we have developed several coatings leads. These HT screening results for the best coating compositions have been validated on the traditional scales of coating formulation and adhesion loss testing. These validation results have confirmed the superb performance of combinatorially developed coatings over conventional coatings on the traditional scale.

  15. Quantum mechanics in chemistry

    CERN Document Server

    Schatz, George C

    2002-01-01

    Intended for graduate and advanced undergraduate students, this text explores quantum mechanical techniques from the viewpoint of chemistry and materials science. Dynamics, symmetry, and formalism are emphasized. An initial review of basic concepts from introductory quantum mechanics is followed by chapters examining symmetry, rotations, and angular momentum addition. Chapter 4 introduces the basic formalism of time-dependent quantum mechanics, emphasizing time-dependent perturbation theory and Fermi's golden rule. Chapter 5 sees this formalism applied to the interaction of radiation and matt

  16. Computational quantum chemistry website

    International Nuclear Information System (INIS)

    1997-01-01

    This report contains the contents of a web page related to research on the development of quantum chemistry methods for computational thermochemistry and the application of quantum chemistry methods to problems in material chemistry and chemical sciences. Research programs highlighted include: Gaussian-2 theory; Density functional theory; Molecular sieve materials; Diamond thin-film growth from buckyball precursors; Electronic structure calculations on lithium polymer electrolytes; Long-distance electronic coupling in donor/acceptor molecules; and Computational studies of NOx reactions in radioactive waste storage

  17. Complementing high-throughput X-ray powder diffraction data with quantum-chemical calculations

    DEFF Research Database (Denmark)

    Naelapaa, Kaisa; van de Streek, Jacco; Rantanen, Jukka

    2012-01-01

    of piroxicam form III. These combined experimental/quantum-chemical methods can provide access to reliable structural information in the course of an intensive experimentally based solid-form screening activity or in other circumstances wherein single crystals might never be viable, for example, for polymorphs...

  18. Quantum chemistry an introduction

    CERN Document Server

    Kauzmann, Walter

    2013-01-01

    Quantum Chemistry: An Introduction provides information pertinent to the fundamental aspects of quantum mechanics. This book presents the theory of partial differentiation equations by using the classical theory of vibrations as a means of developing physical insight into this essential branch of mathematics.Organized into five parts encompassing 16 chapters, this book begins with an overview of how quantum mechanical deductions are made. This text then describes the achievements and limitations of the application of quantum mechanics to chemical problems. Other chapters provide a brief survey

  19. Introductory quantum chemistry

    International Nuclear Information System (INIS)

    Chandra, A.K.

    1974-01-01

    This book on quantum chemistry is primarily intended for university students at the senior undergraduate level. It serves as an aid to the basic understanding of the important concepts of quantum mechanics introduced in the field of chemistry. Various chapters of the book are devoted to the following : (i) Waves and quanta, (ii) Operator concept in quantum chemistry, (iii) Wave mechanics of some simple systems, (iv) Perturbation theory, (v) Many-electron atoms and angular momenta (vi) Molecular orbital theory and its application to the electronic structure of diatomic molecules, (vii) Chemical bonding in polyatomic molecules and (viii) Chemical applications of Hellmann-Feynman theorem. At the end of each chapter, a set of problems is given and the answers to these problems are given at the end of the book. (A.K.)

  20. Fundamentals of quantum chemistry

    CERN Document Server

    House, J E

    2004-01-01

    An introduction to the principles of quantum mechanics needed in physical chemistry. Mathematical tools are presented and developed as needed and only basic calculus, chemistry, and physics is assumed. Applications include atomic and molecular structure, spectroscopy, alpha decay, tunneling, and superconductivity. New edition includes sections on perturbation theory, orbital symmetry of diatomic molecules, the Huckel MO method and Woodward/Hoffman rules as well as a new chapter on SCF and Hartree-Fock methods. * This revised text clearly presents basic q

  1. Quantum dots for a high-throughput Pfu polymerase based multi-round polymerase chain reaction (PCR).

    Science.gov (United States)

    Sang, Fuming; Zhang, Zhizhou; Yuan, Lin; Liu, Deli

    2018-02-26

    Multi-round PCR is an important technique for obtaining enough target DNA from rare DNA resources, and is commonly used in many fields including forensic science, ancient DNA analysis and cancer research. However, multi-round PCR is often aborted, largely due to the accumulation of non-specific amplification during repeated amplifications. Here, we developed a Pfu polymerase based multi-round PCR technique assisted by quantum dots (QDs). Different PCR assays, DNA polymerases (Pfu and Taq), DNA sizes and GC amounts were compared in this study. In the presence of QDs, PCR specificity could be retained even in the ninth-round amplification. Moreover, the longer and more complex the targets were, the earlier the abortion happened in multi-round PCR. However, no obvious enhancement of specificity was found in multi-round PCR using Taq DNA polymerase. Significantly, the fidelity of Pfu polymerase based multi-round PCR was not sacrificed in the presence of QDs. Besides, pre-incubation at 50 °C for an hour had no impact on multi-round PCR performance, which further authenticated the hot start effect of QDs modulated in multi-round PCR. The findings of this study demonstrated that a cost-effective and promising multi-round PCR technique for large-scale and high-throughput sample analysis could be established with high specificity, sensibility and accuracy.

  2. Product Chemistry and Process Efficiency of Biomass Torrefaction, Pyrolysis and Gasification Studied by High-Throughput Techniques and Multivariate Analysis

    Science.gov (United States)

    Xiao, Li

    Despite the great passion and endless efforts on development of renewable energy from biomass, the commercialization and scale up of biofuel production is still under pressure and facing challenges. New ideas and facilities are being tested around the world targeting at reducing cost and improving product value. Cutting edge technologies involving analytical chemistry, statistics analysis, industrial engineering, computer simulation, and mathematics modeling, etc. keep integrating modern elements into this classic research. One of those challenges of commercializing biofuel production is the complexity from chemical composition of biomass feedstock and the products. Because of this, feedstock selection and process optimization cannot be conducted efficiently. This dissertation attempts to further evaluate biomass thermal decomposition process using both traditional methods and advanced technique (Pyrolysis Molecular Beam Mass Spectrometry). Focus has been made on data base generation of thermal decomposition products from biomass at different temperatures, finding out the relationship between traditional methods and advanced techniques, evaluating process efficiency and optimizing reaction conditions, comparison of typically utilized biomass feedstock and new search on innovative species for economical viable feedstock preparation concepts, etc. Lab scale quartz tube reactors and 80il stainless steel sample cups coupled with auto-sampling system were utilized to simulate the complicated reactions happened in real fluidized or entrained flow reactors. Two main high throughput analytical techniques used are Near Infrared Spectroscopy (NIR) and Pyrolysis Molecular Beam Mass Spectrometry (Py-MBMS). Mass balance, carbon balance, and product distribution are presented in detail. Variations of thermal decomposition temperature range from 200°C to 950°C. Feedstocks used in the study involve typical hardwood and softwood (red oak, white oak, yellow poplar, loblolly pine

  3. Handbook of relativistic quantum chemistry

    International Nuclear Information System (INIS)

    Liu, Wenjian

    2017-01-01

    This handbook focuses on the foundations of relativistic quantum mechanics and addresses a number of fundamental issues never covered before in a book. For instance: How can many-body theory be combined with quantum electrodynamics? How can quantum electrodynamics be interfaced with relativistic quantum chemistry? What is the most appropriate relativistic many-electron Hamiltonian? How can we achieve relativistic explicit correlation? How can we formulate relativistic properties? - just to name a few. Since relativistic quantum chemistry is an integral component of computational chemistry, this handbook also supplements the ''Handbook of Computational Chemistry''. Generally speaking, it aims to establish the 'big picture' of relativistic molecular quantum mechanics as the union of quantum electrodynamics and relativistic quantum chemistry. Accordingly, it provides an accessible introduction for readers new to the field, presents advanced methodologies for experts, and discusses possible future perspectives, helping readers understand when/how to apply/develop the methodologies.

  4. Handbook of relativistic quantum chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenjian (ed.) [Peking Univ., Beijing (China). Center for Computational Science and Engineering

    2017-03-01

    This handbook focuses on the foundations of relativistic quantum mechanics and addresses a number of fundamental issues never covered before in a book. For instance: How can many-body theory be combined with quantum electrodynamics? How can quantum electrodynamics be interfaced with relativistic quantum chemistry? What is the most appropriate relativistic many-electron Hamiltonian? How can we achieve relativistic explicit correlation? How can we formulate relativistic properties? - just to name a few. Since relativistic quantum chemistry is an integral component of computational chemistry, this handbook also supplements the ''Handbook of Computational Chemistry''. Generally speaking, it aims to establish the 'big picture' of relativistic molecular quantum mechanics as the union of quantum electrodynamics and relativistic quantum chemistry. Accordingly, it provides an accessible introduction for readers new to the field, presents advanced methodologies for experts, and discusses possible future perspectives, helping readers understand when/how to apply/develop the methodologies.

  5. Quantum chemistry on a superconducting quantum processor

    Energy Technology Data Exchange (ETDEWEB)

    Kaicher, Michael P.; Wilhelm, Frank K. [Theoretical Physics, Saarland University, 66123 Saarbruecken (Germany); Love, Peter J. [Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States)

    2016-07-01

    Quantum chemistry is the most promising civilian application for quantum processors to date. We study its adaptation to superconducting (sc) quantum systems, computing the ground state energy of LiH through a variational hybrid quantum classical algorithm. We demonstrate how interactions native to sc qubits further reduce the amount of quantum resources needed, pushing sc architectures as a near-term candidate for simulations of more complex atoms/molecules.

  6. High Throughput, High Yield Fabrication of High Quantum Efficiency Back-Illuminated Photon Counting, Far UV, UV, and Visible Detector Arrays

    Science.gov (United States)

    Nikzad, Shouleh; Hoenk, M. E.; Carver, A. G.; Jones, T. J.; Greer, F.; Hamden, E.; Goodsall, T.

    2013-01-01

    In this paper we discuss the high throughput end-to-end post fabrication processing of high performance delta-doped and superlattice-doped silicon imagers for UV, visible, and NIR applications. As an example, we present our results on far ultraviolet and ultraviolet quantum efficiency (QE) in a photon counting, detector array. We have improved the QE by nearly an order of magnitude over microchannel plates (MCPs) that are the state-of-the-art UV detectors for many NASA space missions as well as defense applications. These achievements are made possible by precision interface band engineering of Molecular Beam Epitaxy (MBE) and Atomic Layer Deposition (ALD).

  7. Elementary quantum chemistry

    CERN Document Server

    Pilar, Frank L

    2003-01-01

    Useful introductory course and reference covers origins of quantum theory, Schrödinger wave equation, quantum mechanics of simple systems, electron spin, quantum states of atoms, Hartree-Fock self-consistent field method, more. 1990 edition.

  8. Relativistic quantum chemistry on quantum computers

    DEFF Research Database (Denmark)

    Veis, L.; Visnak, J.; Fleig, T.

    2012-01-01

    The past few years have witnessed a remarkable interest in the application of quantum computing for solving problems in quantum chemistry more efficiently than classical computers allow. Very recently, proof-of-principle experimental realizations have been reported. However, so far only...... the nonrelativistic regime (i.e., the Schrodinger equation) has been explored, while it is well known that relativistic effects can be very important in chemistry. We present a quantum algorithm for relativistic computations of molecular energies. We show how to efficiently solve the eigenproblem of the Dirac......-Coulomb Hamiltonian on a quantum computer and demonstrate the functionality of the proposed procedure by numerical simulations of computations of the spin-orbit splitting in the SbH molecule. Finally, we propose quantum circuits with three qubits and nine or ten controlled-NOT (CNOT) gates, which implement a proof...

  9. Remedial mathematics for quantum chemistry

    NARCIS (Netherlands)

    Koopman, L.; Brouwer, N.; Heck, A.; Buma, W.J.

    2008-01-01

    Proper mathematical skills are important for every science course and mathematics-intensive chemistry courses rely on a sound mathematical pre-knowledge. In the first-year quantum chemistry course at this university, it was noticed that many students lack basic mathematical knowledge. To tackle the

  10. Introducing Relativity into Quantum Chemistry

    Science.gov (United States)

    Li, Wai-Kee; Blinder, S. M.

    2011-01-01

    It is not often realized by chemists that the special theory of relativity is behind several aspects of quantum chemistry. The Schrdinger equation itself is based on relations between space-time and energy-momentum four vectors. Electron spin is, of course, the most obvious manifestation of relativity. The chemistry of some heavy elements is…

  11. Chemogenomics: a discipline at the crossroad of high throughput technologies, biomarker research, combinatorial chemistry, genomics, cheminformatics, bioinformatics and artificial intelligence.

    Science.gov (United States)

    Maréchal, Eric

    2008-09-01

    Chemogenomics is the study of the interaction of functional biological systems with exogenous small molecules, or in broader sense the study of the intersection of biological and chemical spaces. Chemogenomics requires expertises in biology, chemistry and computational sciences (bioinformatics, cheminformatics, large scale statistics and machine learning methods) but it is more than the simple apposition of each of these disciplines. Biological entities interacting with small molecules can be isolated proteins or more elaborate systems, from single cells to complete organisms. The biological space is therefore analyzed at various postgenomic levels (genomic, transcriptomic, proteomic or any phenotypic level). The space of small molecules is partially real, corresponding to commercial and academic collections of compounds, and partially virtual, corresponding to the chemical space possibly synthesizable. Synthetic chemistry has developed novel strategies allowing a physical exploration of this universe of possibilities. A major challenge of cheminformatics is to charter the virtual space of small molecules using realistic biological constraints (bioavailability, druggability, structural biological information). Chemogenomics is a descendent of conventional pharmaceutical approaches, since it involves the screening of chemolibraries for their effect on biological targets, and benefits from the advances in the corresponding enabling technologies and the introduction of new biological markers. Screening was originally motivated by the rigorous discovery of new drugs, neglecting and throwing away any molecule that would fail to meet the standards required for a therapeutic treatment. It is now the basis for the discovery of small molecules that might or might not be directly used as drugs, but which have an immense potential for basic research, as probes to explore an increasing number of biological phenomena. Concerns about the environmental impact of chemical industry

  12. High-throughput flow injection analysis mass spectroscopy with networked delivery of color-rendered results. 2. Three-dimensional spectral mapping of 96-well combinatorial chemistry racks.

    Science.gov (United States)

    Görlach, E; Richmond, R; Lewis, I

    1998-08-01

    For the last two years, the mass spectroscopy section of the Novartis Pharma Research Core Technology group has analyzed tens of thousands of multiple parallel synthesis samples from the Novartis Pharma Combinatorial Chemistry program, using an in-house developed automated high-throughput flow injection analysis electrospray ionization mass spectroscopy system. The electrospray spectra of these samples reflect the many structures present after the cleavage step from the solid support. The overall success of the sequential synthesis is mirrored in the purity of the expected end product, but the partial success of individual synthesis steps is evident in the impurities in the mass spectrum. However this latter reaction information, which is of considerable utility to the combinatorial chemist, is effectively hidden from view by the very large number of analyzed samples. This information is now revealed at the workbench of the combinatorial chemist by a novel three-dimensional display of each rack's complete mass spectral ion current using the in-house RackViewer Visual Basic application. Colorization of "forbidden loss" and "forbidden gas-adduct" zones, normalization to expected monoisotopic molecular weight, colorization of ionization intensity, and sorting by row or column were used in combination to highlight systematic patterns in the mass spectroscopy data.

  13. Handbook of computational quantum chemistry

    CERN Document Server

    Cook, David B

    2005-01-01

    Quantum chemistry forms the basis of molecular modeling, a tool widely used to obtain important chemical information and visual images of molecular systems. Recent advances in computing have resulted in considerable developments in molecular modeling, and these developments have led to significant achievements in the design and synthesis of drugs and catalysts. This comprehensive text provides upper-level undergraduates and graduate students with an introduction to the implementation of quantum ideas in molecular modeling, exploring practical applications alongside theoretical explanations.Wri

  14. A high-throughput homogeneous immunoassay based on Förster resonance energy transfer between quantum dots and gold nanoparticles

    International Nuclear Information System (INIS)

    Qian, Jing; Wang, Chengquan; Pan, Xiaohu; Liu, Songqin

    2013-01-01

    Graphical abstract: A Förster resonance energy transfer system by using polyclonal goat anti-CEA antibody labeled luminescent CdTe quantum dots (QDs) as donor and monoclonal goat anti-CEA antibody labeled gold nanoparticles (AuNPs) as acceptor for sensitive detection of tumor marker was proposed. Highlights: ► A homogeneous immunosensing strategy based on FRET for detection of tumor marker was proposed. ► Close of QDs and AuNPs allow the occurrence of quenching the photoluminescence of nano-bio-probes. ► Signal quenching was monitored by a self-developed image analyzer. ► The fluorometric assay format is attractive for widespread carcinoma screening and even field use. -- Abstract: A novel homogeneous immunoassay based on Förster resonance energy transfer for sensitive detection of tumor, e.g., marker with carcinoembryonic antigen (CEA), was proposed. The assay was consisted of polyclonal goat anti-CEA antibody labeled luminescent CdTe quantum dots (QDs) as donor and monoclonal goat anti-CEA antibody labeled gold nanoparticles (AuNPs) as acceptor. In presence of CEA, the bio-affinity between antigen and antibody made the QDs and AuNPs close enough, thus the photoluminescence (PL) quenching of CdTe QDs occurred. The PL properties could be transformed into the fluorometric variation, corresponding to the target antigen concentration, and could be easily monitored and analyzed with the home-made image analysis software. The fluorometric results indicated a linear detection range of 1–110 ng mL −1 for CEA, with a detection limit of 0.3 ng mL −1 . The proposed assay configuration was attractive for carcinoma screening or single sample in point-of-care testing, and even field use. In spite of the limit of available model analyte, this approach could be easily extended to detection of a wide range of biomarkers

  15. A high-throughput homogeneous immunoassay based on Förster resonance energy transfer between quantum dots and gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Jing [School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189 (China); School of Chemistry and Chemical Engineering, Jiangsu University, Zhengjiang 212013 (China); Wang, Chengquan [Changzhou College of Information Technology, Changzhou 213164 (China); Pan, Xiaohu [School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189 (China); Liu, Songqin, E-mail: liusq@seu.edu.cn [School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189 (China)

    2013-02-06

    Graphical abstract: A Förster resonance energy transfer system by using polyclonal goat anti-CEA antibody labeled luminescent CdTe quantum dots (QDs) as donor and monoclonal goat anti-CEA antibody labeled gold nanoparticles (AuNPs) as acceptor for sensitive detection of tumor marker was proposed. Highlights: ► A homogeneous immunosensing strategy based on FRET for detection of tumor marker was proposed. ► Close of QDs and AuNPs allow the occurrence of quenching the photoluminescence of nano-bio-probes. ► Signal quenching was monitored by a self-developed image analyzer. ► The fluorometric assay format is attractive for widespread carcinoma screening and even field use. -- Abstract: A novel homogeneous immunoassay based on Förster resonance energy transfer for sensitive detection of tumor, e.g., marker with carcinoembryonic antigen (CEA), was proposed. The assay was consisted of polyclonal goat anti-CEA antibody labeled luminescent CdTe quantum dots (QDs) as donor and monoclonal goat anti-CEA antibody labeled gold nanoparticles (AuNPs) as acceptor. In presence of CEA, the bio-affinity between antigen and antibody made the QDs and AuNPs close enough, thus the photoluminescence (PL) quenching of CdTe QDs occurred. The PL properties could be transformed into the fluorometric variation, corresponding to the target antigen concentration, and could be easily monitored and analyzed with the home-made image analysis software. The fluorometric results indicated a linear detection range of 1–110 ng mL{sup −1} for CEA, with a detection limit of 0.3 ng mL{sup −1}. The proposed assay configuration was attractive for carcinoma screening or single sample in point-of-care testing, and even field use. In spite of the limit of available model analyte, this approach could be easily extended to detection of a wide range of biomarkers.

  16. Quantum chemistry and scientific calculus

    International Nuclear Information System (INIS)

    Gervais, H.P.

    1988-01-01

    The 1988 progress report of the Polytechnic School research team, concerning the quantum chemistry and the scientific calculus. The research program involves the following topics: the transition metals - carbon monoxide systems, which are a suitable model for the chemisorption phenomena; the introduction of the vibronic perturbations in the magnetic screen constants; the gauge invariance method (used in the calculation of the magnetic perturbations), extended to the case of the static or dynamic electrical polarizabilities. The published papers, the congress communications and the thesis are listed [fr

  17. Computing protein infrared spectroscopy with quantum chemistry.

    Science.gov (United States)

    Besley, Nicholas A

    2007-12-15

    Quantum chemistry is a field of science that has undergone unprecedented advances in the last 50 years. From the pioneering work of Boys in the 1950s, quantum chemistry has evolved from being regarded as a specialized and esoteric discipline to a widely used tool that underpins much of the current research in chemistry today. This achievement was recognized with the award of the 1998 Nobel Prize in Chemistry to John Pople and Walter Kohn. As the new millennium unfolds, quantum chemistry stands at the forefront of an exciting new era. Quantitative calculations on systems of the magnitude of proteins are becoming a realistic possibility, an achievement that would have been unimaginable to the early pioneers of quantum chemistry. In this article we will describe ongoing work towards this goal, focusing on the calculation of protein infrared amide bands directly with quantum chemical methods.

  18. Exploiting Locality in Quantum Computation for Quantum Chemistry.

    Science.gov (United States)

    McClean, Jarrod R; Babbush, Ryan; Love, Peter J; Aspuru-Guzik, Alán

    2014-12-18

    Accurate prediction of chemical and material properties from first-principles quantum chemistry is a challenging task on traditional computers. Recent developments in quantum computation offer a route toward highly accurate solutions with polynomial cost; however, this solution still carries a large overhead. In this Perspective, we aim to bring together known results about the locality of physical interactions from quantum chemistry with ideas from quantum computation. We show that the utilization of spatial locality combined with the Bravyi-Kitaev transformation offers an improvement in the scaling of known quantum algorithms for quantum chemistry and provides numerical examples to help illustrate this point. We combine these developments to improve the outlook for the future of quantum chemistry on quantum computers.

  19. Second quantized approach to quantum chemistry

    International Nuclear Information System (INIS)

    Surjan, P.R.

    1989-01-01

    The subject of this book is the application of the second quantized approach to quantum chemistry. Second quantization is an alternative tool for dealing with many-electron theory. The vast majority of quantum chemical problems are more easily treated using second quantization as a language. This book offers a simple and pedagogical presentation of the theory and some applications. The reader is not supposed to be trained in higher mathematics, though familiarity with elementary quantum mechanics and quantum chemistry is assumed. Besides the basic formalism and standard illustrative applications, some recent topics of quantum chemistry are reviewed in some detail. This book bridges the gap between sophisticated quantum theory and practical quantum chemistry. (orig.)

  20. Quantum chemistry literature data base

    International Nuclear Information System (INIS)

    Ohno, Kimio; Morokuma, Keiji

    1982-01-01

    Ab initio computations of atomic and molecular electronic structure now appear in so many journals that it is very difficult for interested scientistics to locate proper and comprehensive references. This book is designed to help them and contains more than 2500 references to the literature published in the years 1978-1980. These have been gathered from nineteen well-known international core journals by quantum chemists themselves and the result is a thorough bibliography. Each entry is a full reference consisting of the following items: (1) authors, (2) journal name, volume, page and year, (3) compounds, (4) methods of calculation, (5) basis sets, (6) calculated properties, and (7) comments. For easy access to the references, the reader can consult the compound and author indexes. A short article on the reliability of ab initio calculations is included as an appendix; this gives a rough idea about the accuracy of the calculated results reported. As the book has been complied using the resources of a computer data base of quantum chemistry literature, it is particularly up to date and the authors will be able to provide supplements regularly. This bibliography will be an asset to large departments of chemistry and all university libraries. (orig.)

  1. From wave mechanics to quantum chemistry

    International Nuclear Information System (INIS)

    Daudel, R.

    1996-01-01

    The origin of wave mechanics, which is now called quantum mechanics, is evoked. The main stages of the birth of quantum chemistry are related as resulting from the application of quantum mechanics to the study of molecular properties and chemical reactions. (author). 14 refs

  2. Quantum Nanobiology and Biophysical Chemistry

    DEFF Research Database (Denmark)

    2013-01-01

    An introduction was provided in the first issue by way of an Editorial to this special two issue volume of Current Physical Chemistry – “Quantum Nanobiology and Biophysical Chemistry” [1]. The Guest Editors would like to thank all the authors and referees who have contributed to this second issue....... Wu et al. use density functional theory to explore the use of Ni/Fe bimetallic nanotechnology in the bioremediation of decabromo-diphenyl esters. Araújo-Chaves et al. explore the binding and reactivity of Mn(III) porphyrins in the membrane mimetic setting of model liposomal systems. Claussen et al....... demonstrate extremely low detection performance of acyl-homoserine lactone in a biologically relevant system using surface enhanced Raman spectroscopy. Sugihara and Bondar evaluate the influence of methyl-groups and the protein environment on retinal geometries in rhodopsin and bacteriorhodopsin, two...

  3. A Quantum Chemistry Concept Inventory for Physical Chemistry Classes

    Science.gov (United States)

    Dick-Perez, Marilu; Luxford, Cynthia J.; Windus, Theresa L.; Holme, Thomas

    2016-01-01

    A 14-item, multiple-choice diagnostic assessment tool, the quantum chemistry concept inventory or QCCI, is presented. Items were developed based on published student misconceptions and content coverage and then piloted and used in advanced physical chemistry undergraduate courses. In addition to the instrument itself, data from both a pretest,…

  4. Development of a high-throughput real time PCR based on a hot-start alternative for Pfu mediated by quantum dots

    Science.gov (United States)

    Sang, Fuming; Yang, Yang; Yuan, Lin; Ren, Jicun; Zhang, Zhizhou

    2015-09-01

    Hot start (HS) PCR is an excellent alternative for high-throughput real time PCR due to its ability to prevent nonspecific amplification at low temperature. Development of a cost-effective and simple HS PCR technique to guarantee high-throughput PCR specificity and consistency still remains a great challenge. In this study, we systematically investigated the HS characteristics of QDs triggered in real time PCR with EvaGreen and SYBR Green I dyes by the analysis of amplification curves, standard curves and melting curves. Two different kinds of DNA polymerases, Pfu and Taq, were employed. Here we showed that high specificity and efficiency of real time PCR were obtained in a plasmid DNA and an error-prone two-round PCR assay using QD-based HS PCR, even after an hour preincubation at 50 °C before real time PCR. Moreover, the results obtained by QD-based HS PCR were comparable to a commercial Taq antibody DNA polymerase. However, no obvious HS effect of QDs was found in real time PCR using Taq DNA polymerase. The findings of this study demonstrated that a cost-effective high-throughput real time PCR based on QD triggered HS PCR could be established with high consistency, sensitivity and accuracy.Hot start (HS) PCR is an excellent alternative for high-throughput real time PCR due to its ability to prevent nonspecific amplification at low temperature. Development of a cost-effective and simple HS PCR technique to guarantee high-throughput PCR specificity and consistency still remains a great challenge. In this study, we systematically investigated the HS characteristics of QDs triggered in real time PCR with EvaGreen and SYBR Green I dyes by the analysis of amplification curves, standard curves and melting curves. Two different kinds of DNA polymerases, Pfu and Taq, were employed. Here we showed that high specificity and efficiency of real time PCR were obtained in a plasmid DNA and an error-prone two-round PCR assay using QD-based HS PCR, even after an hour

  5. High Throughput Plasma Water Treatment

    Science.gov (United States)

    Mujovic, Selman; Foster, John

    2016-10-01

    The troublesome emergence of new classes of micro-pollutants, such as pharmaceuticals and endocrine disruptors, poses challenges for conventional water treatment systems. In an effort to address these contaminants and to support water reuse in drought stricken regions, new technologies must be introduced. The interaction of water with plasma rapidly mineralizes organics by inducing advanced oxidation in addition to other chemical, physical and radiative processes. The primary barrier to the implementation of plasma-based water treatment is process volume scale up. In this work, we investigate a potentially scalable, high throughput plasma water reactor that utilizes a packed bed dielectric barrier-like geometry to maximize the plasma-water interface. Here, the water serves as the dielectric medium. High-speed imaging and emission spectroscopy are used to characterize the reactor discharges. Changes in methylene blue concentration and basic water parameters are mapped as a function of plasma treatment time. Experimental results are compared to electrostatic and plasma chemistry computations, which will provide insight into the reactor's operation so that efficiency can be assessed. Supported by NSF (CBET 1336375).

  6. Quantum chemistry simulation on quantum computers: theories and experiments.

    Science.gov (United States)

    Lu, Dawei; Xu, Boruo; Xu, Nanyang; Li, Zhaokai; Chen, Hongwei; Peng, Xinhua; Xu, Ruixue; Du, Jiangfeng

    2012-07-14

    It has been claimed that quantum computers can mimic quantum systems efficiently in the polynomial scale. Traditionally, those simulations are carried out numerically on classical computers, which are inevitably confronted with the exponential growth of required resources, with the increasing size of quantum systems. Quantum computers avoid this problem, and thus provide a possible solution for large quantum systems. In this paper, we first discuss the ideas of quantum simulation, the background of quantum simulators, their categories, and the development in both theories and experiments. We then present a brief introduction to quantum chemistry evaluated via classical computers followed by typical procedures of quantum simulation towards quantum chemistry. Reviewed are not only theoretical proposals but also proof-of-principle experimental implementations, via a small quantum computer, which include the evaluation of the static molecular eigenenergy and the simulation of chemical reaction dynamics. Although the experimental development is still behind the theory, we give prospects and suggestions for future experiments. We anticipate that in the near future quantum simulation will become a powerful tool for quantum chemistry over classical computations.

  7. Density functional theory in quantum chemistry

    CERN Document Server

    Tsuneda, Takao

    2014-01-01

    This book examines density functional theory based on the foundation of quantum chemistry. Unconventional in approach, it reviews basic concepts, then describes the physical meanings of state-of-the-art exchange-correlation functionals and their corrections.

  8. High-throughput bioconjugation for enhanced 193 nm photodissociation via droplet phase initiated ion/ion chemistry using a front-end dual spray reactor.

    Science.gov (United States)

    Cotham, Victoria C; Shaw, Jared B; Brodbelt, Jennifer S

    2015-09-15

    Fast online chemical derivatization of peptides with an aromatic label for enhanced 193 nm ultraviolet photodissociation (UVPD) is demonstrated using a dual electrospray reactor implemented on the front-end of a linear ion trap (LIT) mass spectrometer. The reactor facilitates the intersection of protonated peptides with a second population of chromogenic 4-formyl-1,3-benzenedisulfonic acid (FBDSA) anions to promote real-time formation of ion/ion complexes at atmospheric pressure. Subsequent collisional activation of the ion/ion intermediate results in Schiff base formation generated via reaction between a primary amine in the peptide cation and the aldehyde moiety of the FBDSA anion. Utilizing 193 nm UVPD as the subsequent activation step in the MS(3) workflow results in acquisition of greater primary sequence information relative to conventional collision induced dissociation (CID). Furthermore, Schiff-base-modified peptides exhibit on average a 20% increase in UVPD efficiency compared to their unmodified counterparts. Due to the efficiency of covalent labeling achieved with the dual spray reactor, we demonstrate that this strategy can be integrated into a high-throughput LC-MS(n) workflow for rapid derivatization of peptide mixtures.

  9. Simulating chemistry using quantum computers.

    Science.gov (United States)

    Kassal, Ivan; Whitfield, James D; Perdomo-Ortiz, Alejandro; Yung, Man-Hong; Aspuru-Guzik, Alán

    2011-01-01

    The difficulty of simulating quantum systems, well known to quantum chemists, prompted the idea of quantum computation. One can avoid the steep scaling associated with the exact simulation of increasingly large quantum systems on conventional computers, by mapping the quantum system to another, more controllable one. In this review, we discuss to what extent the ideas in quantum computation, now a well-established field, have been applied to chemical problems. We describe algorithms that achieve significant advantages for the electronic-structure problem, the simulation of chemical dynamics, protein folding, and other tasks. Although theory is still ahead of experiment, we outline recent advances that have led to the first chemical calculations on small quantum information processors.

  10. Towards quantum chemistry on a quantum computer.

    Science.gov (United States)

    Lanyon, B P; Whitfield, J D; Gillett, G G; Goggin, M E; Almeida, M P; Kassal, I; Biamonte, J D; Mohseni, M; Powell, B J; Barbieri, M; Aspuru-Guzik, A; White, A G

    2010-02-01

    Exact first-principles calculations of molecular properties are currently intractable because their computational cost grows exponentially with both the number of atoms and basis set size. A solution is to move to a radically different model of computing by building a quantum computer, which is a device that uses quantum systems themselves to store and process data. Here we report the application of the latest photonic quantum computer technology to calculate properties of the smallest molecular system: the hydrogen molecule in a minimal basis. We calculate the complete energy spectrum to 20 bits of precision and discuss how the technique can be expanded to solve large-scale chemical problems that lie beyond the reach of modern supercomputers. These results represent an early practical step toward a powerful tool with a broad range of quantum-chemical applications.

  11. High Throughput Transcriptomics @ USEPA (Toxicology ...

    Science.gov (United States)

    The ideal chemical testing approach will provide complete coverage of all relevant toxicological responses. It should be sensitive and specific It should identify the mechanism/mode-of-action (with dose-dependence). It should identify responses relevant to the species of interest. Responses should ideally be translated into tissue-, organ-, and organism-level effects. It must be economical and scalable. Using a High Throughput Transcriptomics platform within US EPA provides broader coverage of biological activity space and toxicological MOAs and helps fill the toxicological data gap. Slide presentation at the 2016 ToxForum on using High Throughput Transcriptomics at US EPA for broader coverage biological activity space and toxicological MOAs.

  12. Relativistic quantum chemistry on quantum computers

    Czech Academy of Sciences Publication Activity Database

    Veis, Libor; Višňák, Jakub; Fleig, T.; Knecht, S.; Saue, T.; Visscher, L.; Pittner, Jiří

    2012-01-01

    Roč. 85, č. 3 (2012), 030304 ISSN 1050-2947 R&D Projects: GA ČR GA203/08/0626 Institutional support: RVO:61388955 Keywords : simulation * algorithm * computation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.042, year: 2012

  13. High-throughput continuous cryopump

    International Nuclear Information System (INIS)

    Foster, C.A.

    1986-01-01

    A cryopump with a unique method of regeneration which allows continuous operation at high throughput has been constructed and tested. Deuterium was pumped continuously at a throughput of 30 Torr.L/s at a speed of 2000 L/s and a compression ratio of 200. Argon was pumped at a throughput of 60 Torr.L/s at a speed of 1275 L/s. To produce continuous operation of the pump, a method of regeneration that does not thermally cycle the pump is employed. A small chamber (the ''snail'') passes over the pumping surface and removes the frost from it either by mechanical action with a scraper or by local heating. The material removed is topologically in a secondary vacuum system with low conductance into the primary vacuum; thus, the exhaust can be pumped at pressures up to an effective compression ratio determined by the ratio of the pumping speed to the leakage conductance of the snail. The pump, which is all-metal-sealed and dry and which regenerates every 60 s, would be an ideal system for pumping tritium. Potential fusion applications are for mpmp limiters, for repeating pneumatic pellet injection lines, and for the centrifuge pellet injector spin tank, all of which will require pumping tritium at high throughput. Industrial applications requiring ultraclean pumping of corrosive gases at high throughput, such as the reactive ion etch semiconductor process, may also be feasible

  14. Quantum Monte Carlo tunneling from quantum chemistry to quantum annealing

    Science.gov (United States)

    Mazzola, Guglielmo; Smelyanskiy, Vadim N.; Troyer, Matthias

    2017-10-01

    Quantum tunneling is ubiquitous across different fields, from quantum chemical reactions and magnetic materials to quantum simulators and quantum computers. While simulating the real-time quantum dynamics of tunneling is infeasible for high-dimensional systems, quantum tunneling also shows up in quantum Monte Carlo (QMC) simulations, which aim to simulate quantum statistics with resources growing only polynomially with the system size. Here we extend the recent results obtained for quantum spin models [Phys. Rev. Lett. 117, 180402 (2016), 10.1103/PhysRevLett.117.180402], and we study continuous-variable models for proton transfer reactions. We demonstrate that QMC simulations efficiently recover the scaling of ground-state tunneling rates due to the existence of an instanton path, which always connects the reactant state with the product. We discuss the implications of our results in the context of quantum chemical reactions and quantum annealing, where quantum tunneling is expected to be a valuable resource for solving combinatorial optimization problems.

  15. High throughput protein production screening

    Science.gov (United States)

    Beernink, Peter T [Walnut Creek, CA; Coleman, Matthew A [Oakland, CA; Segelke, Brent W [San Ramon, CA

    2009-09-08

    Methods, compositions, and kits for the cell-free production and analysis of proteins are provided. The invention allows for the production of proteins from prokaryotic sequences or eukaryotic sequences, including human cDNAs using PCR and IVT methods and detecting the proteins through fluorescence or immunoblot techniques. This invention can be used to identify optimized PCR and WT conditions, codon usages and mutations. The methods are readily automated and can be used for high throughput analysis of protein expression levels, interactions, and functional states.

  16. Quantum chemistry in environmental pesticide risk assessment.

    Science.gov (United States)

    Villaverde, Juan J; López-Goti, Carmen; Alcamí, Manuel; Lamsabhi, Al Mokhtar; Alonso-Prados, José L; Sandín-España, Pilar

    2017-11-01

    The scientific community and regulatory bodies worldwide, currently promote the development of non-experimental tests that produce reliable data for pesticide risk assessment. The use of standard quantum chemistry methods could allow the development of tools to perform a first screening of compounds to be considered for the experimental studies, improving the risk assessment. This fact results in a better distribution of resources and in better planning, allowing a more exhaustive study of the pesticides and their metabolic products. The current paper explores the potential of quantum chemistry in modelling toxicity and environmental behaviour of pesticides and their by-products by using electronic descriptors obtained computationally. Quantum chemistry has potential to estimate the physico-chemical properties of pesticides, including certain chemical reaction mechanisms and their degradation pathways, allowing modelling of the environmental behaviour of both pesticides and their by-products. In this sense, theoretical methods can contribute to performing a more focused risk assessment of pesticides used in the market, and may lead to higher quality and safer agricultural products. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  17. Faster quantum chemistry simulation on fault-tolerant quantum computers

    International Nuclear Information System (INIS)

    Cody Jones, N; McMahon, Peter L; Yamamoto, Yoshihisa; Whitfield, James D; Yung, Man-Hong; Aspuru-Guzik, Alán; Van Meter, Rodney

    2012-01-01

    Quantum computers can in principle simulate quantum physics exponentially faster than their classical counterparts, but some technical hurdles remain. We propose methods which substantially improve the performance of a particular form of simulation, ab initio quantum chemistry, on fault-tolerant quantum computers; these methods generalize readily to other quantum simulation problems. Quantum teleportation plays a key role in these improvements and is used extensively as a computing resource. To improve execution time, we examine techniques for constructing arbitrary gates which perform substantially faster than circuits based on the conventional Solovay–Kitaev algorithm (Dawson and Nielsen 2006 Quantum Inform. Comput. 6 81). For a given approximation error ϵ, arbitrary single-qubit gates can be produced fault-tolerantly and using a restricted set of gates in time which is O(log ϵ) or O(log log ϵ); with sufficient parallel preparation of ancillas, constant average depth is possible using a method we call programmable ancilla rotations. Moreover, we construct and analyze efficient implementations of first- and second-quantized simulation algorithms using the fault-tolerant arbitrary gates and other techniques, such as implementing various subroutines in constant time. A specific example we analyze is the ground-state energy calculation for lithium hydride. (paper)

  18. High-throughput computational search for strengthening precipitates in alloys

    International Nuclear Information System (INIS)

    Kirklin, S.; Saal, James E.; Hegde, Vinay I.; Wolverton, C.

    2016-01-01

    The search for high-strength alloys and precipitation hardened systems has largely been accomplished through Edisonian trial and error experimentation. Here, we present a novel strategy using high-throughput computational approaches to search for promising precipitate/alloy systems. We perform density functional theory (DFT) calculations of an extremely large space of ∼200,000 potential compounds in search of effective strengthening precipitates for a variety of different alloy matrices, e.g., Fe, Al, Mg, Ni, Co, and Ti. Our search strategy involves screening phases that are likely to produce coherent precipitates (based on small lattice mismatch) and are composed of relatively common alloying elements. When combined with the Open Quantum Materials Database (OQMD), we can computationally screen for precipitates that either have a stable two-phase equilibrium with the host matrix, or are likely to precipitate as metastable phases. Our search produces (for the structure types considered) nearly all currently known high-strength precipitates in a variety of fcc, bcc, and hcp matrices, thus giving us confidence in the strategy. In addition, we predict a number of new, currently-unknown precipitate systems that should be explored experimentally as promising high-strength alloy chemistries.

  19. Per-Olov Löwdin - father of quantum chemistry

    Science.gov (United States)

    Brändas, Erkki J.

    2017-09-01

    During 2016, we celebrate the 100th anniversary of the birth of Per-Olov Löwdin. He was appointed to the first Lehrstuhl in quantum chemistry at Uppsala University in 1960. Löwdin introduced quantum chemistry as a field in its own right by formulating its goals, establishing fundamental concepts, like the correlation energy, the method of configuration interaction, reduced density matrices, natural spin orbitals, charge and bond order matrices, symmetric orthogonalisation, and generalised self-consistent fields. His exposition of partitioning technique and perturbation theory, wave and reaction operators and associated non-linear summation techniques, introduced mathematical rigour and deductive order in the interpretative organisation of the new field. He brought the first computer to Uppsala University and pioneered the initiation of 'electronic brains' and anticipated their significance for quantum chemistry. Perhaps his single most influential contribution to the field was his education of two generations of future faculty in quantum chemistry through Summer Schools in the Scandinavian Mountains, Winter Institutes at Sanibel Island in the Gulf of Mexico. Per-Olov Löwdin founded the book series Advances in Quantum Chemistry and the International Journal of Quantum Chemistry. The evolution of quantum chemistry is appraised, starting from a collection of cross-disciplinary applications of quantum mechanics to the technologically advanced and predominant field of today, virtually used in all branches of chemistry. The scientific work of Per-Olov Löwdin has been crucial for the development of this new important province of science.

  20. Alternative algebraic approaches in quantum chemistry

    International Nuclear Information System (INIS)

    Mezey, Paul G.

    2015-01-01

    Various algebraic approaches of quantum chemistry all follow a common principle: the fundamental properties and interrelations providing the most essential features of a quantum chemical representation of a molecule or a chemical process, such as a reaction, can always be described by algebraic methods. Whereas such algebraic methods often provide precise, even numerical answers, nevertheless their main role is to give a framework that can be elaborated and converted into computational methods by involving alternative mathematical techniques, subject to the constraints and directions provided by algebra. In general, algebra describes sets of interrelations, often phrased in terms of algebraic operations, without much concern with the actual entities exhibiting these interrelations. However, in many instances, the very realizations of two, seemingly unrelated algebraic structures by actual quantum chemical entities or properties play additional roles, and unexpected connections between different algebraic structures are often giving new insight. Here we shall be concerned with two alternative algebraic structures: the fundamental group of reaction mechanisms, based on the energy-dependent topology of potential energy surfaces, and the interrelations among point symmetry groups for various distorted nuclear arrangements of molecules. These two, distinct algebraic structures provide interesting interrelations, which can be exploited in actual studies of molecular conformational and reaction processes. Two relevant theorems will be discussed

  1. Alternative algebraic approaches in quantum chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Mezey, Paul G., E-mail: paul.mezey@gmail.com [Canada Research Chair in Scientific Modeling and Simulation, Department of Chemistry and Department of Physics and Physical Oceanography, Memorial University of Newfoundland, 283 Prince Philip Drive, St. John' s, NL A1B 3X7 (Canada)

    2015-01-22

    Various algebraic approaches of quantum chemistry all follow a common principle: the fundamental properties and interrelations providing the most essential features of a quantum chemical representation of a molecule or a chemical process, such as a reaction, can always be described by algebraic methods. Whereas such algebraic methods often provide precise, even numerical answers, nevertheless their main role is to give a framework that can be elaborated and converted into computational methods by involving alternative mathematical techniques, subject to the constraints and directions provided by algebra. In general, algebra describes sets of interrelations, often phrased in terms of algebraic operations, without much concern with the actual entities exhibiting these interrelations. However, in many instances, the very realizations of two, seemingly unrelated algebraic structures by actual quantum chemical entities or properties play additional roles, and unexpected connections between different algebraic structures are often giving new insight. Here we shall be concerned with two alternative algebraic structures: the fundamental group of reaction mechanisms, based on the energy-dependent topology of potential energy surfaces, and the interrelations among point symmetry groups for various distorted nuclear arrangements of molecules. These two, distinct algebraic structures provide interesting interrelations, which can be exploited in actual studies of molecular conformational and reaction processes. Two relevant theorems will be discussed.

  2. Disciplines, models, and computers: the path to computational quantum chemistry.

    Science.gov (United States)

    Lenhard, Johannes

    2014-12-01

    Many disciplines and scientific fields have undergone a computational turn in the past several decades. This paper analyzes this sort of turn by investigating the case of computational quantum chemistry. The main claim is that the transformation from quantum to computational quantum chemistry involved changes in three dimensions. First, on the side of instrumentation, small computers and a networked infrastructure took over the lead from centralized mainframe architecture. Second, a new conception of computational modeling became feasible and assumed a crucial role. And third, the field of computa- tional quantum chemistry became organized in a market-like fashion and this market is much bigger than the number of quantum theory experts. These claims will be substantiated by an investigation of the so-called density functional theory (DFT), the arguably pivotal theory in the turn to computational quantum chemistry around 1990.

  3. Ab initio quantum chemistry for combustion

    International Nuclear Information System (INIS)

    Page, M.; Lengsfield, B.H.

    1991-01-01

    Advances in theoretical and computational methods, coupled with the rapid development of powerful and inexpensive computers, fuel the current rapid development in computational quantum chemistry (QC). Nowhere is this more evident than in the areas of QC most relevant to combustion: the description of bond breaking and rate phenomena. although the development of faster computers with larger memories has had a major impact on the scope of problems that can be addressed with QC, the development of new theoretical techniques and capabilities is responsible for adding new dimensions in QC and has paved the way for the unification of QC electronic structure calculations with statistical and dynamical models of chemical reactions. These advances will be stressed in this chapter. This paper describes past accomplishments selectively to set the stage for discussion of ideas or techniques that we believe will have significant impact on combustion research. Thus, the focus of the chapter is as much on the future as it is on the past

  4. Quantum chemistry-assisted synthesis route development

    International Nuclear Information System (INIS)

    Hori, Kenji; Sumimoto, Michinori; Murafuji, Toshihiro

    2015-01-01

    We have been investigating “quantum chemistry-assisted synthesis route development” using in silico screenings and applied the method to several targets. Another example was conducted to develop synthesis routes for a urea derivative, namely 1-(4-(trifluoromethyl)-2-oxo-2H-chromen-7-yl)urea. While five synthesis routes were examined, only three routes passed the second in silico screening. Among them, the reaction of 7-amino-4-(trifluoromethyl)-2H-chromen-2-one and O-methyl carbamate with BF 3 as an additive was ranked as the first choice for synthetic work. We were able to experimentally obtain the target compound even though its yield was as low as 21 %. The theoretical result was thus consistent with that observed. The summary of transition state data base (TSDB) is also provided. TSDB is the key to reducing time of in silico screenings

  5. From transistor to trapped-ion computers for quantum chemistry.

    Science.gov (United States)

    Yung, M-H; Casanova, J; Mezzacapo, A; McClean, J; Lamata, L; Aspuru-Guzik, A; Solano, E

    2014-01-07

    Over the last few decades, quantum chemistry has progressed through the development of computational methods based on modern digital computers. However, these methods can hardly fulfill the exponentially-growing resource requirements when applied to large quantum systems. As pointed out by Feynman, this restriction is intrinsic to all computational models based on classical physics. Recently, the rapid advancement of trapped-ion technologies has opened new possibilities for quantum control and quantum simulations. Here, we present an efficient toolkit that exploits both the internal and motional degrees of freedom of trapped ions for solving problems in quantum chemistry, including molecular electronic structure, molecular dynamics, and vibronic coupling. We focus on applications that go beyond the capacity of classical computers, but may be realizable on state-of-the-art trapped-ion systems. These results allow us to envision a new paradigm of quantum chemistry that shifts from the current transistor to a near-future trapped-ion-based technology.

  6. Virtually going green: The role of quantum computational chemistry in reducing pollution and toxicity in chemistry

    Science.gov (United States)

    Stevens, Jonathan

    2017-07-01

    Continuing advances in computational chemistry has permitted quantum mechanical calculation to assist in research in green chemistry and to contribute to the greening of chemical practice. Presented here are recent examples illustrating the contribution of computational quantum chemistry to green chemistry, including the possibility of using computation as a green alternative to experiments, but also illustrating contributions to greener catalysis and the search for greener solvents. Examples of applications of computation to ambitious projects for green synthetic chemistry using carbon dioxide are also presented.

  7. Solutions to selected exercise problems in quantum chemistry and spectroscopy

    DEFF Research Database (Denmark)

    Spanget-Larsen, Jens

    2016-01-01

    Suggested solutions to a number of problems from the collection "Exercise Problems in Quantum Chemistry and Spectroscopy", previously published on ResearchGate (DOI: 10.13140/RG.2.1.4024.8162).......Suggested solutions to a number of problems from the collection "Exercise Problems in Quantum Chemistry and Spectroscopy", previously published on ResearchGate (DOI: 10.13140/RG.2.1.4024.8162)....

  8. High throughput sample processing and automated scoring

    Directory of Open Access Journals (Sweden)

    Gunnar eBrunborg

    2014-10-01

    Full Text Available The comet assay is a sensitive and versatile method for assessing DNA damage in cells. In the traditional version of the assay, there are many manual steps involved and few samples can be treated in one experiment. High throughput modifications have been developed during recent years, and they are reviewed and discussed. These modifications include accelerated scoring of comets; other important elements that have been studied and adapted to high throughput are cultivation and manipulation of cells or tissues before and after exposure, and freezing of treated samples until comet analysis and scoring. High throughput methods save time and money but they are useful also for other reasons: large-scale experiments may be performed which are otherwise not practicable (e.g., analysis of many organs from exposed animals, and human biomonitoring studies, and automation gives more uniform sample treatment and less dependence on operator performance. The high throughput modifications now available vary largely in their versatility, capacity, complexity and costs. The bottleneck for further increase of throughput appears to be the scoring.

  9. High Throughput Analysis of Photocatalytic Water Purification

    NARCIS (Netherlands)

    Sobral Romao, J.I.; Baiao Barata, David; Habibovic, Pamela; Mul, Guido; Baltrusaitis, Jonas

    2014-01-01

    We present a novel high throughput photocatalyst efficiency assessment method based on 96-well microplates and UV-Vis spectroscopy. We demonstrate the reproducibility of the method using methyl orange (MO) decomposition, and compare kinetic data obtained with those provided in the literature for

  10. High-throughput scoring of seed germination

    NARCIS (Netherlands)

    Ligterink, Wilco; Hilhorst, Henk W.M.

    2017-01-01

    High-throughput analysis of seed germination for phenotyping large genetic populations or mutant collections is very labor intensive and would highly benefit from an automated setup. Although very often used, the total germination percentage after a nominated period of time is not very

  11. Quantum mechanics a comprehensive text for chemistry

    CERN Document Server

    Arora, Kishor

    2010-01-01

    This book contains 14 chapters. The text includes the inadequacy of classical mechanics and covers basic and fundamental concepts of quantum mechanics including concepts of transitional, vibration rotation and electronic energies, introduction to concepts of angular momenta, approximatemethods and their application concepts related to electron spin, symmetery concepts and quantum mechanics and ultimately the book features the theories of chemical bonding and use of softwares in quantum mechanics. the text of the book is presented in a lucid manner with ample examples and illustrations wherever

  12. High Throughput Neuro-Imaging Informatics

    Directory of Open Access Journals (Sweden)

    Michael I Miller

    2013-12-01

    Full Text Available This paper describes neuroinformatics technologies at 1 mm anatomical scale based on high throughput 3D functional and structural imaging technologies of the human brain. The core is an abstract pipeline for converting functional and structural imagery into their high dimensional neuroinformatic representations index containing O(E3-E4 discriminating dimensions. The pipeline is based on advanced image analysis coupled to digital knowledge representations in the form of dense atlases of the human brain at gross anatomical scale. We demonstrate the integration of these high-dimensional representations with machine learning methods, which have become the mainstay of other fields of science including genomics as well as social networks. Such high throughput facilities have the potential to alter the way medical images are stored and utilized in radiological workflows. The neuroinformatics pipeline is used to examine cross-sectional and personalized analyses of neuropsychiatric illnesses in clinical applications as well as longitudinal studies. We demonstrate the use of high throughput machine learning methods for supporting (i cross-sectional image analysis to evaluate the health status of individual subjects with respect to the population data, (ii integration of image and non-image information for diagnosis and prognosis.

  13. Quantum information and computation for chemistry

    CERN Document Server

    Kais, Sabre; Rice, Stuart A

    2014-01-01

    Examines the intersection of quantum information and chemical physics The Advances in Chemical Physics series is dedicated to reviewing new and emerging topics as well as the latest developments in traditional areas of study in the field of chemical physics. Each volume features detailed comprehensive analyses coupled with individual points of view that integrate the many disciplines of science that are needed for a full understanding of chemical physics. This volume of the series explores the latest research findings, applications, and new research paths from the quantum information science

  14. High throughput experimentation for the discovery of new catalysts

    International Nuclear Information System (INIS)

    Thomson, S.; Hoffmann, C.; Johann, T.; Wolf, A.; Schmidt, H.-W.; Farrusseng, D.; Schueth, F.

    2002-01-01

    Full text: The use of combinatorial chemistry to obtain new materials has been developed extensively by the pharmaceutical and biochemical industries, but such approaches have been slow to impact on the field of heterogeneous catalysis. The reasons for this lie in with difficulties associated in the synthesis, characterisation and determination of catalytic properties of such materials. In many synthetic and catalytic reactions, the conditions used are difficult to emulate using High Throughput Experimentation (HTE). Furthermore, the ability to screen these catalysts simultaneously in real time, requires the development and/or modification of characterisation methods. Clearly, there is a need for both high throughput synthesis and screening of new and novel reactions, and we describe several new concepts that help to achieve these goals. Although such problems have impeded the development of combinatorial catalysis, the fact remains that many highly attractive processes still exist for which no suitable catalysts have been developed. The ability to decrease the tiFme needed to evaluate catalyst is therefore essential and this makes the use of high throughput techniques highly desirable. In this presentation we will describe the synthesis, catalytic testing, and novel screening methods developed at the Max Planck Institute. Automated synthesis procedures, performed by the use of a modified Gilson pipette robot, will be described, as will the development of two 16 and 49 sample fixed bed reactors and two 25 and 29 sample three phase reactors for catalytic testing. We will also present new techniques for the characterisation of catalysts and catalytic products using standard IR microscopy and infrared focal plane array detection, respectively

  15. Quantum Chemistry; A concise introduction for students of physics, chemistry, biochemistry and materials science

    Science.gov (United States)

    Thakkar, Ajit J.

    2017-09-01

    This book provides non-specialists with a basic understanding of the underlying concepts of quantum chemistry. It is both a text for second- or third-year undergraduates and a reference for researchers who need a quick introduction or refresher. All chemists and many biochemists, materials scientists, engineers, and physicists routinely use spectroscopic measurements and electronic structure computations in their work. The emphasis of Quantum Chemistry on explaining ideas rather than enumerating facts or presenting procedural details makes this an excellent foundation text/reference.

  16. Optimizing qubit resources for quantum chemistry simulations in second quantization on a quantum computer

    International Nuclear Information System (INIS)

    Moll, Nikolaj; Fuhrer, Andreas; Staar, Peter; Tavernelli, Ivano

    2016-01-01

    Quantum chemistry simulations on a quantum computer suffer from the overhead needed for encoding the Fermionic problem in a system of qubits. By exploiting the block diagonality of a Fermionic Hamiltonian, we show that the number of required qubits can be reduced while the number of terms in the Hamiltonian will increase. All operations for this reduction can be performed in operator space. The scheme is conceived as a pre-computational step that would be performed prior to the actual quantum simulation. We apply this scheme to reduce the number of qubits necessary to simulate both the Hamiltonian of the two-site Fermi–Hubbard model and the hydrogen molecule. Both quantum systems can then be simulated with a two-qubit quantum computer. Despite the increase in the number of Hamiltonian terms, the scheme still remains a useful tool to reduce the dimensionality of specific quantum systems for quantum simulators with a limited number of resources. (paper)

  17. High throughput screening method for assessing heterogeneity of microorganisms

    NARCIS (Netherlands)

    Ingham, C.J.; Sprenkels, A.J.; van Hylckama Vlieg, J.E.T.; Bomer, Johan G.; de Vos, W.M.; van den Berg, Albert

    2006-01-01

    The invention relates to the field of microbiology. Provided is a method which is particularly powerful for High Throughput Screening (HTS) purposes. More specific a high throughput method for determining heterogeneity or interactions of microorganisms is provided.

  18. 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

  19. High Throughput PBTK: Open-Source Data and Tools for ...

    Science.gov (United States)

    Presentation on High Throughput PBTK at the PBK Modelling in Risk Assessment meeting in Ispra, Italy Presentation on High Throughput PBTK at the PBK Modelling in Risk Assessment meeting in Ispra, Italy

  20. Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry.

    Science.gov (United States)

    Rappoport, Dmitrij; Galvin, Cooper J; Zubarev, Dmitry Yu; Aspuru-Guzik, Alán

    2014-03-11

    While structures and reactivities of many small molecules can be computed efficiently and accurately using quantum chemical methods, heuristic approaches remain essential for modeling complex structures and large-scale chemical systems. Here, we present a heuristics-aided quantum chemical methodology applicable to complex chemical reaction networks such as those arising in cell metabolism and prebiotic chemistry. Chemical heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chemical structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chemical methodology to the formose reaction reproduces the experimentally observed reaction products, major reaction pathways, and autocatalytic cycles.

  1. Using high throughput experimental data and in silico models to discover alternatives to toxic chromate corrosion inhibitors

    International Nuclear Information System (INIS)

    Winkler, D.A.; Breedon, M.; White, P.; Hughes, A.E.; Sapper, E.D.; Cole, I.

    2016-01-01

    Highlights: • We screened a large library of organic compounds as replacements for toxic chromates. • High throughput automated corrosion testing was used to assess inhibitor performance. • Robust, predictive machine learning models of corrosion inhibition were developed. • Models indicated molecular features contributing to performance of organic inhibitors. • We also showed that quantum chemistry descriptors do not correlate with performance. - Abstract: Restrictions on the use of toxic chromate-based corrosion inhibitors have created important issues for the aerospace and other industries. Benign alternatives that offer similar or superior performance are needed. We used high throughput experiments to assess 100 small organic molecules as potential inhibitors of corrosion in aerospace aluminium alloys AA2024 and AA7075. We generated robust, predictive, quantitative computational models of inhibitor efficiency at two pH values using these data. The models identified molecular features of inhibitor molecules that had the greatest impact on corrosion inhibition. Models can be used to discover better corrosion inhibitors by screening libraries of organic compounds for candidates with high corrosion inhibition.

  2. Advances in analytical tools for high throughput strain engineering

    DEFF Research Database (Denmark)

    Marcellin, Esteban; Nielsen, Lars Keld

    2018-01-01

    The emergence of inexpensive, base-perfect genome editing is revolutionising biology. Modern industrial biotechnology exploits the advances in genome editing in combination with automation, analytics and data integration to build high-throughput automated strain engineering pipelines also known...... as biofoundries. Biofoundries replace the slow and inconsistent artisanal processes used to build microbial cell factories with an automated design–build–test cycle, considerably reducing the time needed to deliver commercially viable strains. Testing and hence learning remains relatively shallow, but recent...... advances in analytical chemistry promise to increase the depth of characterization possible. Analytics combined with models of cellular physiology in automated systems biology pipelines should enable deeper learning and hence a steeper pitch of the learning cycle. This review explores the progress...

  3. High-Throughput Scoring of Seed Germination.

    Science.gov (United States)

    Ligterink, Wilco; Hilhorst, Henk W M

    2017-01-01

    High-throughput analysis of seed germination for phenotyping large genetic populations or mutant collections is very labor intensive and would highly benefit from an automated setup. Although very often used, the total germination percentage after a nominated period of time is not very informative as it lacks information about start, rate, and uniformity of germination, which are highly indicative of such traits as dormancy, stress tolerance, and seed longevity. The calculation of cumulative germination curves requires information about germination percentage at various time points. We developed the GERMINATOR package: a simple, highly cost-efficient, and flexible procedure for high-throughput automatic scoring and evaluation of germination that can be implemented without the use of complex robotics. The GERMINATOR package contains three modules: (I) design of experimental setup with various options to replicate and randomize samples; (II) automatic scoring of germination based on the color contrast between the protruding radicle and seed coat on a single image; and (III) curve fitting of cumulative germination data and the extraction, recap, and visualization of the various germination parameters. GERMINATOR is a freely available package that allows the monitoring and analysis of several thousands of germination tests, several times a day by a single person.

  4. High throughput nonparametric probability density estimation.

    Science.gov (United States)

    Farmer, Jenny; Jacobs, Donald

    2018-01-01

    In high throughput applications, such as those found in bioinformatics and finance, it is important to determine accurate probability distribution functions despite only minimal information about data characteristics, and without using human subjectivity. Such an automated process for univariate data is implemented to achieve this goal by merging the maximum entropy method with single order statistics and maximum likelihood. The only required properties of the random variables are that they are continuous and that they are, or can be approximated as, independent and identically distributed. A quasi-log-likelihood function based on single order statistics for sampled uniform random data is used to empirically construct a sample size invariant universal scoring function. Then a probability density estimate is determined by iteratively improving trial cumulative distribution functions, where better estimates are quantified by the scoring function that identifies atypical fluctuations. This criterion resists under and over fitting data as an alternative to employing the Bayesian or Akaike information criterion. Multiple estimates for the probability density reflect uncertainties due to statistical fluctuations in random samples. Scaled quantile residual plots are also introduced as an effective diagnostic to visualize the quality of the estimated probability densities. Benchmark tests show that estimates for the probability density function (PDF) converge to the true PDF as sample size increases on particularly difficult test probability densities that include cases with discontinuities, multi-resolution scales, heavy tails, and singularities. These results indicate the method has general applicability for high throughput statistical inference.

  5. Modeling Steroidogenesis Disruption Using High-Throughput ...

    Science.gov (United States)

    Environmental chemicals can elicit endocrine disruption by altering steroid hormone biosynthesis and metabolism (steroidogenesis) causing adverse reproductive and developmental effects. Historically, a lack of assays resulted in few chemicals having been evaluated for effects on steroidogenesis. The steroidogenic pathway is a series of hydroxylation and dehydrogenation steps carried out by CYP450 and hydroxysteroid dehydrogenase enzymes, yet the only enzyme in the pathway for which a high-throughput screening (HTS) assay has been developed is aromatase (CYP19A1), responsible for the aromatization of androgens to estrogens. Recently, the ToxCast HTS program adapted the OECD validated H295R steroidogenesis assay using human adrenocortical carcinoma cells into a high-throughput model to quantitatively assess the concentration-dependent (0.003-100 µM) effects of chemicals on 10 steroid hormones including progestagens, androgens, estrogens and glucocorticoids. These results, in combination with two CYP19A1 inhibition assays, comprise a large dataset amenable to clustering approaches supporting the identification and characterization of putative mechanisms of action (pMOA) for steroidogenesis disruption. In total, 514 chemicals were tested in all CYP19A1 and steroidogenesis assays. 216 chemicals were identified as CYP19A1 inhibitors in at least one CYP19A1 assay. 208 of these chemicals also altered hormone levels in the H295R assay, suggesting 96% sensitivity in the

  6. Preliminary High-Throughput Metagenome Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Dusheyko, Serge; Furman, Craig; Pangilinan, Jasmyn; Shapiro, Harris; Tu, Hank

    2007-03-26

    Metagenome data sets present a qualitatively different assembly problem than traditional single-organism whole-genome shotgun (WGS) assembly. The unique aspects of such projects include the presence of a potentially large number of distinct organisms and their representation in the data set at widely different fractions. In addition, multiple closely related strains could be present, which would be difficult to assemble separately. Failure to take these issues into account can result in poor assemblies that either jumble together different strains or which fail to yield useful results. The DOE Joint Genome Institute has sequenced a number of metagenomic projects and plans to considerably increase this number in the coming year. As a result, the JGI has a need for high-throughput tools and techniques for handling metagenome projects. We present the techniques developed to handle metagenome assemblies in a high-throughput environment. This includes a streamlined assembly wrapper, based on the JGI?s in-house WGS assembler, Jazz. It also includes the selection of sensible defaults targeted for metagenome data sets, as well as quality control automation for cleaning up the raw results. While analysis is ongoing, we will discuss preliminary assessments of the quality of the assembly results (http://fames.jgi-psf.org).

  7. Quantum Chemistry of Solids LCAO Treatment of Crystals and Nanostructures

    CERN Document Server

    Evarestov, Robert A

    2012-01-01

    Quantum Chemistry of Solids delivers a comprehensive account of the main features and possibilities of LCAO methods for the first principles calculations of electronic structure of periodic systems. The first part describes the basic theory underlying the LCAO methods  applied to periodic systems and the use of Hartree-Fock(HF), Density Function theory(DFT) and hybrid Hamiltonians. The translation and site symmetry consideration is included to establish connection between k-space solid –state physics and real-space quantum chemistry. The inclusion of electron correlation effects for periodic systems is considered on the basis of localized crystalline orbitals. The possibilities of LCAO methods for chemical bonding analysis in periodic systems are discussed. The second part deals with the applications of LCAO methods  for calculations of bulk crystal properties, including magnetic ordering and crystal structure optimization.  In the second edition two new chapters are added in the application part II of t...

  8. Quantum Chemistry via Walks in Determinant Space

    Energy Technology Data Exchange (ETDEWEB)

    Umrigar, Cyrus J. [Cornell Univ., Ithaca, NY (United States)

    2016-01-05

    There are many chemical questions of practical interest to the DOE that could be answered if there were an electronic structure method that provided consistently accurate results for all systems at an affordable computational cost. The coupled cluster method with single, double and perturbative triple excitations (CCSD(T)) is the most frequently used high-order method, but it has known deficiencies, e.g., in the description of stretched bonds. The full configuration interaction (FCI) method is the most robust method for treating electronic correlations, but it is little used because its computational cost scales exponentially in the size of the system. The largest calculation that has been done to date employed 10 billion determinants. In this regard, there was a major advance in 2010. The Alavi group at Cambridge University developed a stochastic approach to FCI --- combining it with ideas from quantum Monte Carlo (QMC) --- called FCIQMC, that allows one to go to a far larger number of determinants in certain circumstances. The computational cost is exponential in the system and basis size but with a much reduced exponent compared to conventional FCI. In this project Umrigar's group made several major improvements to the FCIQMC method that increased its efficiency by many orders of magnitude. In addition this project resulted in a cross-fertilization of ideas between the FCIQMC method, the older phaseless auxilliary-field quantum Monte Carlo (AFQMC) method developed by Zhang and Krakauer (two of the PI's of this project), and symmetry-restored wavefunctions developed by Scuseria (also a PI of this project).

  9. High-Throughput Analysis of Enzyme Activities

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Guoxin [Iowa State Univ., Ames, IA (United States)

    2007-01-01

    High-throughput screening (HTS) techniques have been applied to many research fields nowadays. Robot microarray printing technique and automation microtiter handling technique allows HTS performing in both heterogeneous and homogeneous formats, with minimal sample required for each assay element. In this dissertation, new HTS techniques for enzyme activity analysis were developed. First, patterns of immobilized enzyme on nylon screen were detected by multiplexed capillary system. The imaging resolution is limited by the outer diameter of the capillaries. In order to get finer images, capillaries with smaller outer diameters can be used to form the imaging probe. Application of capillary electrophoresis allows separation of the product from the substrate in the reaction mixture, so that the product doesn't have to have different optical properties with the substrate. UV absorption detection allows almost universal detection for organic molecules. Thus, no modifications of either the substrate or the product molecules are necessary. This technique has the potential to be used in screening of local distribution variations of specific bio-molecules in a tissue or in screening of multiple immobilized catalysts. Another high-throughput screening technique is developed by directly monitoring the light intensity of the immobilized-catalyst surface using a scientific charge-coupled device (CCD). Briefly, the surface of enzyme microarray is focused onto a scientific CCD using an objective lens. By carefully choosing the detection wavelength, generation of product on an enzyme spot can be seen by the CCD. Analyzing the light intensity change over time on an enzyme spot can give information of reaction rate. The same microarray can be used for many times. Thus, high-throughput kinetic studies of hundreds of catalytic reactions are made possible. At last, we studied the fluorescence emission spectra of ADP and obtained the detection limits for ADP under three different

  10. NWChem: Quantum Chemistry Simulations at Scale

    Energy Technology Data Exchange (ETDEWEB)

    Apra, Edoardo; Kowalski, Karol; Hammond, Jeff R.; Klemm, Michael

    2015-01-17

    Methods based on quantum mechanics equations have been developed since the 1930's with the purpose of accurately studying the electronic structure of molecules. However, it is only during the last two decades that intense development of new computational algorithms has opened the possibility of performing accurate simulations of challenging molecular processes with high-order many-body methods. A wealth of evidence indicates that the proper inclusion of instantaneous interactions between electrons (or the so-called electron correlation effects) is indispensable for the accurate characterization of chemical reactivity, molecular properties, and interactions of light with matter. The availability of reliable methods for benchmarking of medium-size molecular systems provides also a unique chance to propagate high-level accuracy across spatial scales through the multiscale methodologies. Some of these methods have potential to utilize computational resources in an effi*cient way since they are characterized by high numerical complexity and appropriate level of data granularity, which can be effi*ciently distributed over multi-processor architectures. The broad spectrum of coupled cluster (CC) methods falls into this class of methodologies. Several recent CC implementations clearly demonstrated the scalability of CC formalisms on architectures composed of hundreds thousand computational cores. In this context NWChem provides a collection of Tensor Contraction Engine (TCE) generated parallel implementations of various coupled cluster methods capable of taking advantage of many thousand of cores on leadership class parallel architectures.

  11. High-Throughput Process Development for Biopharmaceuticals.

    Science.gov (United States)

    Shukla, Abhinav A; Rameez, Shahid; Wolfe, Leslie S; Oien, Nathan

    2017-11-14

    The ability to conduct multiple experiments in parallel significantly reduces the time that it takes to develop a manufacturing process for a biopharmaceutical. This is particularly significant before clinical entry, because process development and manufacturing are on the "critical path" for a drug candidate to enter clinical development. High-throughput process development (HTPD) methodologies can be similarly impactful during late-stage development, both for developing the final commercial process as well as for process characterization and scale-down validation activities that form a key component of the licensure filing package. This review examines the current state of the art for HTPD methodologies as they apply to cell culture, downstream purification, and analytical techniques. In addition, we provide a vision of how HTPD activities across all of these spaces can integrate to create a rapid process development engine that can accelerate biopharmaceutical drug development. Graphical Abstract.

  12. Spiers Memorial Lecture. Quantum chemistry: the first seventy years.

    Science.gov (United States)

    McWeeny, Roy

    2007-01-01

    Present-day theoretical chemistry is rooted in Quantum Mechanics. The aim of the opening lecture is to trace the evolution of Quantum Chemistry from the Heitler-London paper of 1927 up to the end of the last century, emphasizing concepts rather than calculations. The importance of symmetry concepts became evident in the early years: one thinks of the necessary anti-symmetry of the wave function under electron permutations, the Pauli principle, the aufbau scheme, and the classification of spectroscopic states. But for chemists perhaps the key concept is embodied in the Hellmann-Feynman theorem, which provides a pictorial interpretation of chemical bonding in terms of classical electrostatic forces exerted on the nuclei by the electron distribution. Much of the lecture is concerned with various electron distribution functions--the electron density, the current density, the spin density, and other 'property densities'--and with their use in interpreting both molecular structure and molecular properties. Other topics touched upon include Response theory and propagators; Chemical groups in molecules and the group function approach; Atoms in molecules and Bader's theory; Electron correlation and the 'pair function'. Finally, some long-standing controversies, in particular the EPR paradox, are re-examined in the context of molecular dissociation. By admitting the concept of symmetry breaking, along with the use of the von Neumann-Dirac statistical ensemble, orthodox quantum mechanics can lead to a convincing picture of the dissociation mechanism.

  13. AOPs and Biomarkers: Bridging High Throughput Screening ...

    Science.gov (United States)

    As high throughput screening (HTS) plays a larger role in toxicity testing, camputational toxicology has emerged as a critical component in interpreting the large volume of data produced. Computational models designed to quantify potential adverse effects based on HTS data will benefit from additional data sources that connect the magnitude of perturbation from the in vitro system to a level of concern at the organism or population level. The adverse outcome pathway (AOP) concept provides an ideal framework for combining these complementary data. Recent international efforts under the auspices of the Organization for Economic Co-operation and Development (OECD) have resulted in an AOP wiki designed to house formal descriptions of AOPs suitable for use in regulatory decision making. Recent efforts have built upon this to include an ontology describing the AOP with linkages to biological pathways, physiological terminology, and taxonomic applicability domains. Incorporation of an AOP network tool developed by the U.S. Army Corps of Engineers also allows consideration of cumulative risk from chemical and non-chemical stressors. Biomarkers are an important complement to formal AOP descriptions, particularly when dealing with susceptible subpopulations or lifestages in human health risk assessment. To address the issue of nonchemical stressors than may modify effects of criteria air pollutants, a novel method was used to integrate blood gene expression data with hema

  14. Uncertainty Quantification in High Throughput Screening ...

    Science.gov (United States)

    Using uncertainty quantification, we aim to improve the quality of modeling data from high throughput screening assays for use in risk assessment. ToxCast is a large-scale screening program that analyzes thousands of chemicals using over 800 assays representing hundreds of biochemical and cellular processes, including endocrine disruption, cytotoxicity, and zebrafish development. Over 2.6 million concentration response curves are fit to models to extract parameters related to potency and efficacy. Models built on ToxCast results are being used to rank and prioritize the toxicological risk of tested chemicals and to predict the toxicity of tens of thousands of chemicals not yet tested in vivo. However, the data size also presents challenges. When fitting the data, the choice of models, model selection strategy, and hit call criteria must reflect the need for computational efficiency and robustness, requiring hard and somewhat arbitrary cutoffs. When coupled with unavoidable noise in the experimental concentration response data, these hard cutoffs cause uncertainty in model parameters and the hit call itself. The uncertainty will then propagate through all of the models built on the data. Left unquantified, this uncertainty makes it difficult to fully interpret the data for risk assessment. We used bootstrap resampling methods to quantify the uncertainty in fitting models to the concentration response data. Bootstrap resampling determines confidence intervals for

  15. Relativistic quantum chemistry the fundamental theory of molecular science

    CERN Document Server

    Reiher, Markus

    2014-01-01

    Einstein proposed his theory of special relativity in 1905. For a long time it was believed that this theory has no significant impact on chemistry. This view changed in the 1970s when it was realized that (nonrelativistic) Schrödinger quantum mechanics yields results on molecular properties that depart significantly from experimental results. Especially when heavy elements are involved, these quantitative deviations can be so large that qualitative chemical reasoning and understanding is affected. For this to grasp the appropriate many-electron theory has rapidly evolved. Nowadays relativist

  16. Development of massively parallel quantum chemistry program SMASH

    Energy Technology Data Exchange (ETDEWEB)

    Ishimura, Kazuya [Department of Theoretical and Computational Molecular Science, Institute for Molecular Science 38 Nishigo-Naka, Myodaiji, Okazaki, Aichi 444-8585 (Japan)

    2015-12-31

    A massively parallel program for quantum chemistry calculations SMASH was released under the Apache License 2.0 in September 2014. The SMASH program is written in the Fortran90/95 language with MPI and OpenMP standards for parallelization. Frequently used routines, such as one- and two-electron integral calculations, are modularized to make program developments simple. The speed-up of the B3LYP energy calculation for (C{sub 150}H{sub 30}){sub 2} with the cc-pVDZ basis set (4500 basis functions) was 50,499 on 98,304 cores of the K computer.

  17. Development of massively parallel quantum chemistry program SMASH

    International Nuclear Information System (INIS)

    Ishimura, Kazuya

    2015-01-01

    A massively parallel program for quantum chemistry calculations SMASH was released under the Apache License 2.0 in September 2014. The SMASH program is written in the Fortran90/95 language with MPI and OpenMP standards for parallelization. Frequently used routines, such as one- and two-electron integral calculations, are modularized to make program developments simple. The speed-up of the B3LYP energy calculation for (C 150 H 30 ) 2 with the cc-pVDZ basis set (4500 basis functions) was 50,499 on 98,304 cores of the K computer

  18. Cold molecules: Progress in quantum engineering of chemistry and quantum matter

    Science.gov (United States)

    Bohn, John L.; Rey, Ana Maria; Ye, Jun

    2017-09-01

    Cooling atoms to ultralow temperatures has produced a wealth of opportunities in fundamental physics, precision metrology, and quantum science. The more recent application of sophisticated cooling techniques to molecules, which has been more challenging to implement owing to the complexity of molecular structures, has now opened the door to the longstanding goal of precisely controlling molecular internal and external degrees of freedom and the resulting interaction processes. This line of research can leverage fundamental insights into how molecules interact and evolve to enable the control of reaction chemistry and the design and realization of a range of advanced quantum materials.

  19. Ultraspecific probes for high throughput HLA typing

    Directory of Open Access Journals (Sweden)

    Eggers Rick

    2009-02-01

    Full Text Available Abstract Background The variations within an individual's HLA (Human Leukocyte Antigen genes have been linked to many immunological events, e.g. susceptibility to disease, response to vaccines, and the success of blood, tissue, and organ transplants. Although the microarray format has the potential to achieve high-resolution typing, this has yet to be attained due to inefficiencies of current probe design strategies. Results We present a novel three-step approach for the design of high-throughput microarray assays for HLA typing. This approach first selects sequences containing the SNPs present in all alleles of the locus of interest and next calculates the number of base changes necessary to convert a candidate probe sequences to the closest subsequence within the set of sequences that are likely to be present in the sample including the remainder of the human genome in order to identify those candidate probes which are "ultraspecific" for the allele of interest. Due to the high specificity of these sequences, it is possible that preliminary steps such as PCR amplification are no longer necessary. Lastly, the minimum number of these ultraspecific probes is selected such that the highest resolution typing can be achieved for the minimal cost of production. As an example, an array was designed and in silico results were obtained for typing of the HLA-B locus. Conclusion The assay presented here provides a higher resolution than has previously been developed and includes more alleles than previously considered. Based upon the in silico and preliminary experimental results, we believe that the proposed approach can be readily applied to any highly polymorphic gene system.

  20. 20180311 - High Throughput Transcriptomics: From screening to pathways (SOT 2018)

    Science.gov (United States)

    The EPA ToxCast effort has screened thousands of chemicals across hundreds of high-throughput in vitro screening assays. The project is now leveraging high-throughput transcriptomic (HTTr) technologies to substantially expand its coverage of biological pathways. The first HTTr sc...

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

    Science.gov (United States)

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

  2. High Throughput Determinations of Critical Dosing Parameters (IVIVE workshop)

    Science.gov (United States)

    High throughput toxicokinetics (HTTK) is an approach that allows for rapid estimations of TK for hundreds of environmental chemicals. HTTK-based reverse dosimetry (i.e, reverse toxicokinetics or RTK) is used in order to convert high throughput in vitro toxicity screening (HTS) da...

  3. Evaluating High Throughput Toxicokinetics and Toxicodynamics for IVIVE (WC10)

    Science.gov (United States)

    High-throughput screening (HTS) generates in vitro data for characterizing potential chemical hazard. TK models are needed to allow in vitro to in vivo extrapolation (IVIVE) to real world situations. The U.S. EPA has created a public tool (R package “httk” for high throughput tox...

  4. Patterning cell using Si-stencil for high-throughput assay

    KAUST Repository

    Wu, Jinbo

    2011-01-01

    In this communication, we report a newly developed cell pattering methodology by a silicon-based stencil, which exhibited advantages such as easy handling, reusability, hydrophilic surface and mature fabrication technologies. Cell arrays obtained by this method were used to investigate cell growth under a temperature gradient, which demonstrated the possibility of studying cell behavior in a high-throughput assay. This journal is © The Royal Society of Chemistry 2011.

  5. High-throughput characterization methods for lithium batteries

    Directory of Open Access Journals (Sweden)

    Yingchun Lyu

    2017-09-01

    Full Text Available The development of high-performance lithium ion batteries requires the discovery of new materials and the optimization of key components. By contrast with traditional one-by-one method, high-throughput method can synthesize and characterize a large number of compositionally varying samples, which is able to accelerate the pace of discovery, development and optimization process of materials. Because of rapid progress in thin film and automatic control technologies, thousands of compounds with different compositions could be synthesized rapidly right now, even in a single experiment. However, the lack of rapid or combinatorial characterization technologies to match with high-throughput synthesis methods, limit the application of high-throughput technology. Here, we review a series of representative high-throughput characterization methods used in lithium batteries, including high-throughput structural and electrochemical characterization methods and rapid measuring technologies based on synchrotron light sources.

  6. Expression of results in quantum chemistry physical chemistry division commission on physicochemical symbols, terminology and units

    CERN Document Server

    Whiffen, D H

    2013-01-01

    Expression of Results in Quantum Chemistry recommends the appropriate insertion of physical constants in the output information of a theoretical paper in order to make the numerical end results of theoretical work easily transformed to SI units by the reader. The acceptance of this recommendation would circumvent the need for a set of atomic units each with its own symbol and name. It is the traditional use of the phrase """"atomic units"""" in this area which has obscured the real problem. The four SI dimensions of length, mass, time, and current require four physical constants to be permitte

  7. High-throughput screening of chemicals as functional ...

    Science.gov (United States)

    Identifying chemicals that provide a specific function within a product, yet have minimal impact on the human body or environment, is the goal of most formulation chemists and engineers practicing green chemistry. We present a methodology to identify potential chemical functional substitutes from large libraries of chemicals using machine learning based models. We collect and analyze publicly available information on the function of chemicals in consumer products or industrial processes to identify a suite of harmonized function categories suitable for modeling. We use structural and physicochemical descriptors for these chemicals to build 41 quantitative structure–use relationship (QSUR) models for harmonized function categories using random forest classification. We apply these models to screen a library of nearly 6400 chemicals with available structure information for potential functional substitutes. Using our Functional Use database (FUse), we could identify uses for 3121 chemicals; 4412 predicted functional uses had a probability of 80% or greater. We demonstrate the potential application of the models to high-throughput (HT) screening for “candidate alternatives” by merging the valid functional substitute classifications with hazard metrics developed from HT screening assays for bioactivity. A descriptor set could be obtained for 6356 Tox21 chemicals that have undergone a battery of HT in vitro bioactivity screening assays. By applying QSURs, we wer

  8. 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).

  9. The unitary-group formulation of quantum chemistry

    International Nuclear Information System (INIS)

    Campbell, L.L.

    1990-01-01

    The major part of this dissertation establishes group theoretical techniques that are applicable to the quantum-mechanical many-body atomic and molecular problems. Several matrix element evaluation methods for many-body states are developed. The generator commutation method using generator states is presented for the first time as a complete algorithm, and a computer implementation of the method is developed. A major result of this work is the development of a new method of calculation called the freeon tensor product (FTP) method. This method is much simpler and for many purposes superior to the GUGA procedure (graphical unitary group approach), widely used in configuration interaction calculations. This dissertation is also concerned with the prediction of atomic spectra. In principle spectra can be computed by the methods of ab initio quantum chemistry. In practice these computations are difficult, expensive, time consuming, and not uniformly successful. In this dissertation, the author employs a semi-empirical group theoretical analysis of discrete spectra is the exact analog of the Fourier analysis of continuous functions. In particular, he focuses on the spectra of atoms with incomplete p, d, and f shells. The formulas and techniques are derived in a fashion that apply equally well for more complex systems, as well as the isofreeon model of spherical nuclei

  10. High throughput screening of starch structures using carbohydrate microarrays

    DEFF Research Database (Denmark)

    Tanackovic, Vanja; Rydahl, Maja Gro; Pedersen, Henriette Lodberg

    2016-01-01

    In this study we introduce the starch-recognising carbohydrate binding module family 20 (CBM20) from Aspergillus niger for screening biological variations in starch molecular structure using high throughput carbohydrate microarray technology. Defined linear, branched and phosphorylated...

  11. High-Throughput Analysis and Automation for Glycomics Studies

    NARCIS (Netherlands)

    Shubhakar, A.; Reiding, K.R.; Gardner, R.A.; Spencer, D.I.R.; Fernandes, D.L.; Wuhrer, M.

    2015-01-01

    This review covers advances in analytical technologies for high-throughput (HTP) glycomics. Our focus is on structural studies of glycoprotein glycosylation to support biopharmaceutical realization and the discovery of glycan biomarkers for human disease. For biopharmaceuticals, there is increasing

  12. MIPHENO: Data normalization for high throughput metabolic analysis.

    Science.gov (United States)

    High throughput methodologies such as microarrays, mass spectrometry and plate-based small molecule screens are increasingly used to facilitate discoveries from gene function to drug candidate identification. These large-scale experiments are typically carried out over the course...

  13. High throughput octal alpha/gamma spectrometer for low level bioassay estimations

    International Nuclear Information System (INIS)

    Bhasin, B.D.; Shirke, S.H.; Suri, M.M.; Vaidya, P.P.; Ghodgaonkar, M.D.

    1995-01-01

    The present paper describes the development of a high throughput octal alpha spectrometry system specially developed for the estimation of low levels of actinides in bioassay and environmental samples. The system processes simultaneously the outputs coming from eight independent detectors. It can be configured to simultaneously record low level alpha and gamma spectra. The high throughput is achieved by using a prioritised multiplexer router. The prioritised multiplexing and routing coupled with fast 8K ADC (conversion time 20 μsec) allow simultaneous acquisition of multiple spectra without any significant loss in counts. The dual (8K, 24bit) port memory facilitates easy online viewing of spectrum buildup. A menu driven user friendly software makes the operating system convenient to use. A specially developed software provides built-in routines for processing the spectra and estimating the isotopic activity. The interactive mode of software provides easy identification of isotopes compatible with the separation chemistry of different actinides. (author). 6 refs., 2 figs

  14. Solved and unsolved problems in relativistic quantum chemistry

    International Nuclear Information System (INIS)

    Kutzelnigg, Werner

    2012-01-01

    Graphical abstract: The graphical abstract represents the Dirac-Coulomb Hamiltonian in Fock space in a diagrammatic notation. A line (vertical or slanted) with an upgoing arrow represents an eletron, with a downgoing arrow a positron. A cross in the first line means the potential created by a nucleus, a broken line represents the Coulomb interaction between electrons and positrons. Highlights: ► Relativistic many-electron theory needs a Fock space and a field-dependent vacuum. ► A good starting point is QED in Coulomb gauge without transversal photons. ► The Dirac underworld picture is obsolete. ► A kinetically balanced even-tempered Gaussian basis is complete. ► ‘Quantum chemistry in Fock space is preferable over QED. - Abstract: A hierarchy of approximations in relativistic many-electron theory is discussed that starts with the Dirac equation and its expansion in a kinetically balanced basis, via a formulation of non-interacting electrons in Fock space (which is the only consistent way to deal with negative-energy states). The most straightforward approximate Hamiltonian for interacting electrons is derived from quantum electrodynamics (QED) in Coulomb gauge with the neglect of transversal photons. This allows an exact (non-perturbative) decoupling of the electromagnetic field from the fermionic field. The electric interaction of the fermions is non-retarded and non-quantized. The quantization of the fermionic field leads to a polarizable vacuum. The simplest (but somewhat problematic) approximation is a no-pair projected theory with external-field projectors. The Dirac-Coulomb operator in configuration space (first quantization) is not acceptable, even if the Brown–Ravenhall disease is much less virulent than often claimed. Effects of transversal photons, such as the Breit interaction and renormalized self-interaction can be taken care of perturbatively at the end, but there are still many open questions.

  15. Application of the CRAY-1 for quantum chemistry calculations

    International Nuclear Information System (INIS)

    Saunders, V.R.; Guest, M.F.

    1982-01-01

    The following steps in a typical quantum chemistry calculation will be considered: 1. Gaussian integrals evaluation. 2. Hartree-Fock computation of an uncorrelated wavefunction. 3. 4-index transformation of two-electron integrals. 4. Configuration interaction calculations of a correlated wavefunction. In all the above steps we have found that algorithms may be devised which formulate the problem as being dominated by a series of matrix multiplications: R=AB, where A (or B) is sparse. A routine for performing the sparse matrix multiply has been prepared with a maximum measured performance of 147 M flops. When this routine is used in our applications packages, overall performance of approximately 50, 100 and 120 M flops are observed for steps 1, 3 and 4, respectively. The result in step 2 is not so successful, as effective implementation of the matrix multiplication requires efficient performance of data gather and scatter sequences (not vectorisable on the CRAY-1), and a performance of 10 M flops is observed. The importance of gather/scatter sequences in such operations as file sorting is pointed out. The present performance is compared with that previously obtained on CDC 7600 equipment and from this data we deduce the cost-effectiveness of the CRAY-1 in our field. (orig.)

  16. A High-Throughput Biological Calorimetry Core: Steps to Startup, Run, and Maintain a Multiuser Facility.

    Science.gov (United States)

    Yennawar, Neela H; Fecko, Julia A; Showalter, Scott A; Bevilacqua, Philip C

    2016-01-01

    Many labs have conventional calorimeters where denaturation and binding experiments are setup and run one at a time. While these systems are highly informative to biopolymer folding and ligand interaction, they require considerable manual intervention for cleaning and setup. As such, the throughput for such setups is limited typically to a few runs a day. With a large number of experimental parameters to explore including different buffers, macromolecule concentrations, temperatures, ligands, mutants, controls, replicates, and instrument tests, the need for high-throughput automated calorimeters is on the rise. Lower sample volume requirements and reduced user intervention time compared to the manual instruments have improved turnover of calorimetry experiments in a high-throughput format where 25 or more runs can be conducted per day. The cost and efforts to maintain high-throughput equipment typically demands that these instruments be housed in a multiuser core facility. We describe here the steps taken to successfully start and run an automated biological calorimetry facility at Pennsylvania State University. Scientists from various departments at Penn State including Chemistry, Biochemistry and Molecular Biology, Bioengineering, Biology, Food Science, and Chemical Engineering are benefiting from this core facility. Samples studied include proteins, nucleic acids, sugars, lipids, synthetic polymers, small molecules, natural products, and virus capsids. This facility has led to higher throughput of data, which has been leveraged into grant support, attracting new faculty hire and has led to some exciting publications. © 2016 Elsevier Inc. All rights reserved.

  17. The high throughput biomedicine unit at the institute for molecular medicine Finland: high throughput screening meets precision medicine.

    Science.gov (United States)

    Pietiainen, Vilja; Saarela, Jani; von Schantz, Carina; Turunen, Laura; Ostling, Paivi; Wennerberg, Krister

    2014-05-01

    The High Throughput Biomedicine (HTB) unit at the Institute for Molecular Medicine Finland FIMM was established in 2010 to serve as a national and international academic screening unit providing access to state of the art instrumentation for chemical and RNAi-based high throughput screening. The initial focus of the unit was multiwell plate based chemical screening and high content microarray-based siRNA screening. However, over the first four years of operation, the unit has moved to a more flexible service platform where both chemical and siRNA screening is performed at different scales primarily in multiwell plate-based assays with a wide range of readout possibilities with a focus on ultraminiaturization to allow for affordable screening for the academic users. In addition to high throughput screening, the equipment of the unit is also used to support miniaturized, multiplexed and high throughput applications for other types of research such as genomics, sequencing and biobanking operations. Importantly, with the translational research goals at FIMM, an increasing part of the operations at the HTB unit is being focused on high throughput systems biological platforms for functional profiling of patient cells in personalized and precision medicine projects.

  18. High-throughput screening to identify inhibitors of lysine demethylases.

    Science.gov (United States)

    Gale, Molly; Yan, Qin

    2015-01-01

    Lysine demethylases (KDMs) are epigenetic regulators whose dysfunction is implicated in the pathology of many human diseases including various types of cancer, inflammation and X-linked intellectual disability. Particular demethylases have been identified as promising therapeutic targets, and tremendous efforts are being devoted toward developing suitable small-molecule inhibitors for clinical and research use. Several High-throughput screening strategies have been developed to screen for small-molecule inhibitors of KDMs, each with advantages and disadvantages in terms of time, cost, effort, reliability and sensitivity. In this Special Report, we review and evaluate the High-throughput screening methods utilized for discovery of novel small-molecule KDM inhibitors.

  19. High throughput materials research and development for lithium ion batteries

    Directory of Open Access Journals (Sweden)

    Parker Liu

    2017-09-01

    Full Text Available Development of next generation batteries requires a breakthrough in materials. Traditional one-by-one method, which is suitable for synthesizing large number of sing-composition material, is time-consuming and costly. High throughput and combinatorial experimentation, is an effective method to synthesize and characterize huge amount of materials over a broader compositional region in a short time, which enables to greatly speed up the discovery and optimization of materials with lower cost. In this work, high throughput and combinatorial materials synthesis technologies for lithium ion battery research are discussed, and our efforts on developing such instrumentations are introduced.

  20. Towards a high throughput droplet-based agglutination assay

    KAUST Repository

    Kodzius, Rimantas; Castro, David; Foulds, Ian G.

    2013-01-01

    This work demonstrates the detection method for a high throughput droplet based agglutination assay system. Using simple hydrodynamic forces to mix and aggregate functionalized microbeads we avoid the need to use magnetic assistance or mixing structures. The concentration of our target molecules was estimated by agglutination strength, obtained through optical image analysis. Agglutination in droplets was performed with flow rates of 150 µl/min and occurred in under a minute, with potential to perform high-throughput measurements. The lowest target concentration detected in droplet microfluidics was 0.17 nM, which is three orders of magnitude more sensitive than a conventional card based agglutination assay.

  1. Towards a high throughput droplet-based agglutination assay

    KAUST Repository

    Kodzius, Rimantas

    2013-10-22

    This work demonstrates the detection method for a high throughput droplet based agglutination assay system. Using simple hydrodynamic forces to mix and aggregate functionalized microbeads we avoid the need to use magnetic assistance or mixing structures. The concentration of our target molecules was estimated by agglutination strength, obtained through optical image analysis. Agglutination in droplets was performed with flow rates of 150 µl/min and occurred in under a minute, with potential to perform high-throughput measurements. The lowest target concentration detected in droplet microfluidics was 0.17 nM, which is three orders of magnitude more sensitive than a conventional card based agglutination assay.

  2. Meeting Report: High-Throughput Technologies for In Vivo Imaging Agents

    Directory of Open Access Journals (Sweden)

    Robert J. Gillies

    2005-04-01

    Full Text Available Combinatorial chemistry and high-throughput screening have become standard tools for discovering new drug candidates with suitable pharmacological properties. Now, those same technologies are starting to be applied to the problem of discovering novel in vivo imaging agents. Important differences in the biological and pharmacological properties needed for imaging agents, compared to those for a therapeutic agent, require new screening methods that emphasize those characteristics, such as optimized residence time and tissue specificity, that make for a good imaging agent candidate.

  3. Optimization and high-throughput screening of antimicrobial peptides.

    Science.gov (United States)

    Blondelle, Sylvie E; Lohner, Karl

    2010-01-01

    While a well-established process for lead compound discovery in for-profit companies, high-throughput screening is becoming more popular in basic and applied research settings in academia. The development of combinatorial libraries combined with easy and less expensive access to new technologies have greatly contributed to the implementation of high-throughput screening in academic laboratories. While such techniques were earlier applied to simple assays involving single targets or based on binding affinity, they have now been extended to more complex systems such as whole cell-based assays. In particular, the urgent need for new antimicrobial compounds that would overcome the rapid rise of drug-resistant microorganisms, where multiple target assays or cell-based assays are often required, has forced scientists to focus onto high-throughput technologies. Based on their existence in natural host defense systems and their different mode of action relative to commercial antibiotics, antimicrobial peptides represent a new hope in discovering novel antibiotics against multi-resistant bacteria. The ease of generating peptide libraries in different formats has allowed a rapid adaptation of high-throughput assays to the search for novel antimicrobial peptides. Similarly, the availability nowadays of high-quantity and high-quality antimicrobial peptide data has permitted the development of predictive algorithms to facilitate the optimization process. This review summarizes the various library formats that lead to de novo antimicrobial peptide sequences as well as the latest structural knowledge and optimization processes aimed at improving the peptides selectivity.

  4. HTTK: R Package for High-Throughput Toxicokinetics

    Science.gov (United States)

    Thousands of chemicals have been profiled by high-throughput screening programs such as ToxCast and Tox21; these chemicals are tested in part because most of them have limited or no data on hazard, exposure, or toxicokinetics. Toxicokinetic models aid in predicting tissue concent...

  5. Fun with High Throughput Toxicokinetics (CalEPA webinar)

    Science.gov (United States)

    Thousands of chemicals have been profiled by high-throughput screening (HTS) programs such as ToxCast and Tox21. These chemicals are tested in part because there are limited or no data on hazard, exposure, or toxicokinetics (TK). TK models aid in predicting tissue concentrations ...

  6. High-throughput cloning and expression in recalcitrant bacteria

    NARCIS (Netherlands)

    Geertsma, Eric R.; Poolman, Bert

    We developed a generic method for high-throughput cloning in bacteria that are less amenable to conventional DNA manipulations. The method involves ligation-independent cloning in an intermediary Escherichia coli vector, which is rapidly converted via vector-backbone exchange (VBEx) into an

  7. Enzyme free cloning for high throughput gene cloning and expression

    NARCIS (Netherlands)

    de Jong, R.N.; Daniëls, M.; Kaptein, R.; Folkers, G.E.

    2006-01-01

    Structural and functional genomics initiatives significantly improved cloning methods over the past few years. Although recombinational cloning is highly efficient, its costs urged us to search for an alternative high throughput (HTP) cloning method. We implemented a modified Enzyme Free Cloning

  8. High-throughput bioinformatics with the Cyrille2 pipeline system.

    NARCIS (Netherlands)

    Fiers, M.W.E.J.; Burgt, van der A.; Datema, E.; Groot, de J.C.W.; Ham, van R.C.H.J.

    2008-01-01

    Background - Modern omics research involves the application of high-throughput technologies that generate vast volumes of data. These data need to be pre-processed, analyzed and integrated with existing knowledge through the use of diverse sets of software tools, models and databases. The analyses

  9. Principles of conjugating quantum dots to proteins via carbodiimide chemistry

    International Nuclear Information System (INIS)

    Song Fayi; Chan, Warren C W

    2011-01-01

    The covalent coupling of nanomaterials to bio-recognition molecules is a critical intermediate step in using nanomaterials for biology and medicine. Here we investigate the carbodiimide-mediated conjugation of fluorescent quantum dots to different proteins (e.g., immunoglobulin G, bovine serum albumin, and horseradish peroxidase). To enable these studies, we developed a simple method to isolate quantum dot bioconjugates from unconjugated quantum dots. The results show that the reactant concentrations and protein type will impact the overall number of proteins conjugated onto the surfaces of the quantum dots, homogeneity of the protein–quantum dot conjugate population, quantum efficiency, binding avidity, and enzymatic kinetics. We propose general principles that should be followed for the successful coupling of proteins to quantum dots.

  10. Enabling new capabilities and insights from quantum chemistry by using component architectures

    International Nuclear Information System (INIS)

    Janssen, C L; Kenny, J P; Nielsen, I M B; Krishnan, M; Gurumoorthi, V; Valeev, E F; Windus, T L

    2006-01-01

    Steady performance gains in computing power, as well as improvements in Scientific computing algorithms, are making possible the study of coupled physical phenomena of great extent and complexity. The software required for such studies is also very complex and requires contributions from experts in multiple disciplines. We have investigated the use of the Common Component Architecture (CCA) as a mechanism to tackle some of the resulting software engineering challenges in quantum chemistry, focusing on three specific application areas. In our first application, we have developed interfaces permitting solvers and quantum chemistry packages to be readily exchanged. This enables our quantum chemistry packages to be used with alternative solvers developed by specialists, remedying deficiencies we discovered in the native solvers provided in each of the quantum chemistry packages. The second application involves development of a set of components designed to improve utilization of parallel machines by allowing multiple components to execute concurrently on subsets of the available processors. This was found to give substantial improvements in parallel scalability. Our final application is a set of components permitting different quantum chemistry packages to interchange intermediate data. These components enabled the investigation of promising new methods for obtaining accurate thermochemical data for reactions involving heavy elements

  11. Problems and solutions in quantum chemistry and physics

    CERN Document Server

    Johnson, Charles S

    1988-01-01

    Unusually varied problems, with detailed solutions, cover quantum mechanics, wave mechanics, angular momentum, molecular spectroscopy, scattering theory, more. 280 problems, plus 139 supplementary exercises.

  12. Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl-1H-benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors.

    Science.gov (United States)

    Cernak, Tim; Gesmundo, Nathan J; Dykstra, Kevin; Yu, Yang; Wu, Zhicai; Shi, Zhi-Cai; Vachal, Petr; Sperbeck, Donald; He, Shuwen; Murphy, Beth Ann; Sonatore, Lisa; Williams, Steven; Madeira, Maria; Verras, Andreas; Reiter, Maud; Lee, Claire Heechoon; Cuff, James; Sherer, Edward C; Kuethe, Jeffrey; Goble, Stephen; Perrotto, Nicholas; Pinto, Shirly; Shen, Dong-Ming; Nargund, Ravi; Balkovec, James; DeVita, Robert J; Dreher, Spencer D

    2017-05-11

    Miniaturization and parallel processing play an important role in the evolution of many technologies. We demonstrate the application of miniaturized high-throughput experimentation methods to resolve synthetic chemistry challenges on the frontlines of a lead optimization effort to develop diacylglycerol acyltransferase (DGAT1) inhibitors. Reactions were performed on ∼1 mg scale using glass microvials providing a miniaturized high-throughput experimentation capability that was used to study a challenging S N Ar reaction. The availability of robust synthetic chemistry conditions discovered in these miniaturized investigations enabled the development of structure-activity relationships that ultimately led to the discovery of soluble, selective, and potent inhibitors of DGAT1.

  13. Human development VIII: a theory of "deep" quantum chemistry and cell consciousness: quantum chemistry controls genes and biochemistry to give cells and higher organisms consciousness and complex behavior.

    Science.gov (United States)

    Ventegodt, Søren; Hermansen, Tyge Dahl; Flensborg-Madsen, Trine; Nielsen, Maj Lyck; Merrick, Joav

    2006-11-14

    Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it "sees", and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occam's razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules' orbitals make one huge "cell-orbital", which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants) and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness.

  14. Interactive Simulations to Support Quantum Mechanics Instruction for Chemistry Students

    Science.gov (United States)

    Kohnle, Antje; Benfield, Cory; Hahner, Georg; Paetkau, Mark

    2017-01-01

    The QuVis Quantum Mechanics Visualization Project provides freely available research-based interactive simulations with accompanying activities for the teaching and learning of quantum mechanics across a wide range of topics and levels. This article gives an overview of some of the simulations and describes their use in an introductory physical…

  15. High throughput 16S rRNA gene amplicon sequencing

    DEFF Research Database (Denmark)

    Nierychlo, Marta; Larsen, Poul; Jørgensen, Mads Koustrup

    S rRNA gene amplicon sequencing has been developed over the past few years and is now ready to use for more comprehensive studies related to plant operation and optimization thanks to short analysis time, low cost, high throughput, and high taxonomic resolution. In this study we show how 16S r......RNA gene amplicon sequencing can be used to reveal factors of importance for the operation of full-scale nutrient removal plants related to settling problems and floc properties. Using optimized DNA extraction protocols, indexed primers and our in-house Illumina platform, we prepared multiple samples...... be correlated to the presence of the species that are regarded as “strong” and “weak” floc formers. In conclusion, 16S rRNA gene amplicon sequencing provides a high throughput approach for a rapid and cheap community profiling of activated sludge that in combination with multivariate statistics can be used...

  16. High-throughput theoretical design of lithium battery materials

    International Nuclear Information System (INIS)

    Ling Shi-Gang; Gao Jian; Xiao Rui-Juan; Chen Li-Quan

    2016-01-01

    The rapid evolution of high-throughput theoretical design schemes to discover new lithium battery materials is reviewed, including high-capacity cathodes, low-strain cathodes, anodes, solid state electrolytes, and electrolyte additives. With the development of efficient theoretical methods and inexpensive computers, high-throughput theoretical calculations have played an increasingly important role in the discovery of new materials. With the help of automatic simulation flow, many types of materials can be screened, optimized and designed from a structural database according to specific search criteria. In advanced cell technology, new materials for next generation lithium batteries are of great significance to achieve performance, and some representative criteria are: higher energy density, better safety, and faster charge/discharge speed. (topical review)

  17. A CRISPR CASe for High-Throughput Silencing

    Directory of Open Access Journals (Sweden)

    Jacob eHeintze

    2013-10-01

    Full Text Available Manipulation of gene expression on a genome-wide level is one of the most important systematic tools in the post-genome era. Such manipulations have largely been enabled by expression cloning approaches using sequence-verified cDNA libraries, large-scale RNA interference libraries (shRNA or siRNA and zinc finger nuclease technologies. More recently, the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated (Cas9-mediated gene editing technology has been described that holds great promise for future use of this technology in genomic manipulation. It was suggested that the CRISPR system has the potential to be used in high-throughput, large-scale loss of function screening. Here we discuss some of the challenges in engineering of CRISPR/Cas genomic libraries and some of the aspects that need to be addressed in order to use this technology on a high-throughput scale.

  18. High-Throughput Thermodynamic Modeling and Uncertainty Quantification for ICME

    Science.gov (United States)

    Otis, Richard A.; Liu, Zi-Kui

    2017-05-01

    One foundational component of the integrated computational materials engineering (ICME) and Materials Genome Initiative is the computational thermodynamics based on the calculation of phase diagrams (CALPHAD) method. The CALPHAD method pioneered by Kaufman has enabled the development of thermodynamic, atomic mobility, and molar volume databases of individual phases in the full space of temperature, composition, and sometimes pressure for technologically important multicomponent engineering materials, along with sophisticated computational tools for using the databases. In this article, our recent efforts will be presented in terms of developing new computational tools for high-throughput modeling and uncertainty quantification based on high-throughput, first-principles calculations and the CALPHAD method along with their potential propagations to downstream ICME modeling and simulations.

  19. High throughput electrophysiology: new perspectives for ion channel drug discovery

    DEFF Research Database (Denmark)

    Willumsen, Niels J; Bech, Morten; Olesen, Søren-Peter

    2003-01-01

    Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels....... A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct...... characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion...

  20. Reverse Phase Protein Arrays for High-throughput Toxicity Screening

    DEFF Research Database (Denmark)

    Pedersen, Marlene Lemvig; Block, Ines; List, Markus

    High-throughput screening is extensively applied for identification of drug targets and drug discovery and recently it found entry into toxicity testing. Reverse phase protein arrays (RPPAs) are used widespread for quantification of protein markers. We reasoned that RPPAs also can be utilized...... beneficially in automated high-throughput toxicity testing. An advantage of using RPPAs is that, in addition to the baseline toxicity readout, they allow testing of multiple markers of toxicity, such as inflammatory responses, which do not necessarily cumulate in cell death. We used transfection of si......RNAs with known killing effects as a model system to demonstrate that RPPA-based protein quantification can serve as substitute readout of cell viability, hereby reliably reflecting toxicity. In terms of automation, cell exposure, protein harvest, serial dilution and sample reformatting were performed using...

  1. A high-throughput multiplex method adapted for GMO detection.

    Science.gov (United States)

    Chaouachi, Maher; Chupeau, Gaëlle; Berard, Aurélie; McKhann, Heather; Romaniuk, Marcel; Giancola, Sandra; Laval, Valérie; Bertheau, Yves; Brunel, Dominique

    2008-12-24

    A high-throughput multiplex assay for the detection of genetically modified organisms (GMO) was developed on the basis of the existing SNPlex method designed for SNP genotyping. This SNPlex assay allows the simultaneous detection of up to 48 short DNA sequences (approximately 70 bp; "signature sequences") from taxa endogenous reference genes, from GMO constructions, screening targets, construct-specific, and event-specific targets, and finally from donor organisms. This assay avoids certain shortcomings of multiplex PCR-based methods already in widespread use for GMO detection. The assay demonstrated high specificity and sensitivity. The results suggest that this assay is reliable, flexible, and cost- and time-effective for high-throughput GMO detection.

  2. High-throughput epitope identification for snakebite antivenom

    DEFF Research Database (Denmark)

    Engmark, Mikael; De Masi, Federico; Laustsen, Andreas Hougaard

    Insight into the epitopic recognition pattern for polyclonal antivenoms is a strong tool for accurate prediction of antivenom cross-reactivity and provides a basis for design of novel antivenoms. In this work, a high-throughput approach was applied to characterize linear epitopes in 966 individua...... toxins from pit vipers (Crotalidae) using the ICP Crotalidae antivenom. Due to an abundance of snake venom metalloproteinases and phospholipase A2s in the venoms used for production of the investigated antivenom, this study focuses on these toxin families.......Insight into the epitopic recognition pattern for polyclonal antivenoms is a strong tool for accurate prediction of antivenom cross-reactivity and provides a basis for design of novel antivenoms. In this work, a high-throughput approach was applied to characterize linear epitopes in 966 individual...

  3. High-throughput optical system for HDES hyperspectral imager

    Science.gov (United States)

    Václavík, Jan; Melich, Radek; Pintr, Pavel; Pleštil, Jan

    2015-01-01

    Affordable, long-wave infrared hyperspectral imaging calls for use of an uncooled FPA with high-throughput optics. This paper describes the design of the optical part of a stationary hyperspectral imager in a spectral range of 7-14 um with a field of view of 20°×10°. The imager employs a push-broom method made by a scanning mirror. High throughput and a demand for simplicity and rigidity led to a fully refractive design with highly aspheric surfaces and off-axis positioning of the detector array. The design was optimized to exploit the machinability of infrared materials by the SPDT method and a simple assemblage.

  4. Computational tools for high-throughput discovery in biology

    OpenAIRE

    Jones, Neil Christopher

    2007-01-01

    High throughput data acquisition technology has inarguably transformed the landscape of the life sciences, in part by making possible---and necessary---the computational disciplines of bioinformatics and biomedical informatics. These fields focus primarily on developing tools for analyzing data and generating hypotheses about objects in nature, and it is in this context that we address three pressing problems in the fields of the computational life sciences which each require computing capaci...

  5. Development of rapid high throughput biodosimetry tools for radiological triage

    International Nuclear Information System (INIS)

    Balajee, Adayabalam S.; Escalona, Maria; Smith, Tammy; Ryan, Terri; Dainiak, Nicholas

    2018-01-01

    Accidental or intentional radiological or nuclear (R/N) disasters constitute a major threat around the globe that can affect several tens, hundreds and thousands of humans. Currently available cytogenetic biodosimeters are time consuming and laborious to perform making them impractical for triage scenarios. Therefore, it is imperative to develop high throughput techniques which will enable timely assessment of personalized dose for making an appropriate 'life-saving' clinical decision

  6. High-throughput sequence alignment using Graphics Processing Units

    Directory of Open Access Journals (Sweden)

    Trapnell Cole

    2007-12-01

    Full Text Available Abstract Background The recent availability of new, less expensive high-throughput DNA sequencing technologies has yielded a dramatic increase in the volume of sequence data that must be analyzed. These data are being generated for several purposes, including genotyping, genome resequencing, metagenomics, and de novo genome assembly projects. Sequence alignment programs such as MUMmer have proven essential for analysis of these data, but researchers will need ever faster, high-throughput alignment tools running on inexpensive hardware to keep up with new sequence technologies. Results This paper describes MUMmerGPU, an open-source high-throughput parallel pairwise local sequence alignment program that runs on commodity Graphics Processing Units (GPUs in common workstations. MUMmerGPU uses the new Compute Unified Device Architecture (CUDA from nVidia to align multiple query sequences against a single reference sequence stored as a suffix tree. By processing the queries in parallel on the highly parallel graphics card, MUMmerGPU achieves more than a 10-fold speedup over a serial CPU version of the sequence alignment kernel, and outperforms the exact alignment component of MUMmer on a high end CPU by 3.5-fold in total application time when aligning reads from recent sequencing projects using Solexa/Illumina, 454, and Sanger sequencing technologies. Conclusion MUMmerGPU is a low cost, ultra-fast sequence alignment program designed to handle the increasing volume of data produced by new, high-throughput sequencing technologies. MUMmerGPU demonstrates that even memory-intensive applications can run significantly faster on the relatively low-cost GPU than on the CPU.

  7. A Functional High-Throughput Assay of Myelination in Vitro

    Science.gov (United States)

    2014-07-01

    Human induced pluripotent stem cells, hydrogels, 3D culture, electrophysiology, high-throughput assay 16. SECURITY CLASSIFICATION OF: 17...image the 3D rat dorsal root ganglion ( DRG ) cultures with sufficiently low background as to detect electrically-evoked depolarization events, as...of voltage-sensitive dyes. 8    We have made substantial progress in Task 4.1. We have fabricated neural fiber tracts from DRG explants and

  8. High throughput electrophysiology: new perspectives for ion channel drug discovery

    DEFF Research Database (Denmark)

    Willumsen, Niels J; Bech, Morten; Olesen, Søren-Peter

    2003-01-01

    . A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct....... The introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery....

  9. Intel: High Throughput Computing Collaboration: A CERN openlab / Intel collaboration

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    The Intel/CERN High Throughput Computing Collaboration studies the application of upcoming Intel technologies to the very challenging environment of the LHC trigger and data-acquisition systems. These systems will need to transport and process many terabits of data every second, in some cases with tight latency constraints. Parallelisation and tight integration of accelerators and classical CPU via Intel's OmniPath fabric are the key elements in this project.

  10. Using quantum chemistry muscle to flex massive systems: How to respond to something perturbing

    Energy Technology Data Exchange (ETDEWEB)

    Bertoni, Colleen [Iowa State Univ., Ames, IA (United States)

    2016-12-17

    Computational chemistry uses the theoretical advances of quantum mechanics and the algorithmic and hardware advances of computer science to give insight into chemical problems. It is currently possible to do highly accurate quantum chemistry calculations, but the most accurate methods are very computationally expensive. Thus it is only feasible to do highly accurate calculations on small molecules, since typically more computationally efficient methods are also less accurate. The overall goal of my dissertation work has been to try to decrease the computational expense of calculations without decreasing the accuracy. In particular, my dissertation work focuses on fragmentation methods, intermolecular interactions methods, analytic gradients, and taking advantage of new hardware.

  11. High-throughput bioinformatics with the Cyrille2 pipeline system

    Directory of Open Access Journals (Sweden)

    de Groot Joost CW

    2008-02-01

    Full Text Available Abstract Background Modern omics research involves the application of high-throughput technologies that generate vast volumes of data. These data need to be pre-processed, analyzed and integrated with existing knowledge through the use of diverse sets of software tools, models and databases. The analyses are often interdependent and chained together to form complex workflows or pipelines. Given the volume of the data used and the multitude of computational resources available, specialized pipeline software is required to make high-throughput analysis of large-scale omics datasets feasible. Results We have developed a generic pipeline system called Cyrille2. The system is modular in design and consists of three functionally distinct parts: 1 a web based, graphical user interface (GUI that enables a pipeline operator to manage the system; 2 the Scheduler, which forms the functional core of the system and which tracks what data enters the system and determines what jobs must be scheduled for execution, and; 3 the Executor, which searches for scheduled jobs and executes these on a compute cluster. Conclusion The Cyrille2 system is an extensible, modular system, implementing the stated requirements. Cyrille2 enables easy creation and execution of high throughput, flexible bioinformatics pipelines.

  12. High-Throughput Block Optical DNA Sequence Identification.

    Science.gov (United States)

    Sagar, Dodderi Manjunatha; Korshoj, Lee Erik; Hanson, Katrina Bethany; Chowdhury, Partha Pratim; Otoupal, Peter Britton; Chatterjee, Anushree; Nagpal, Prashant

    2018-01-01

    Optical techniques for molecular diagnostics or DNA sequencing generally rely on small molecule fluorescent labels, which utilize light with a wavelength of several hundred nanometers for detection. Developing a label-free optical DNA sequencing technique will require nanoscale focusing of light, a high-throughput and multiplexed identification method, and a data compression technique to rapidly identify sequences and analyze genomic heterogeneity for big datasets. Such a method should identify characteristic molecular vibrations using optical spectroscopy, especially in the "fingerprinting region" from ≈400-1400 cm -1 . Here, surface-enhanced Raman spectroscopy is used to demonstrate label-free identification of DNA nucleobases with multiplexed 3D plasmonic nanofocusing. While nanometer-scale mode volumes prevent identification of single nucleobases within a DNA sequence, the block optical technique can identify A, T, G, and C content in DNA k-mers. The content of each nucleotide in a DNA block can be a unique and high-throughput method for identifying sequences, genes, and other biomarkers as an alternative to single-letter sequencing. Additionally, coupling two complementary vibrational spectroscopy techniques (infrared and Raman) can improve block characterization. These results pave the way for developing a novel, high-throughput block optical sequencing method with lossy genomic data compression using k-mer identification from multiplexed optical data acquisition. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. The Evolution of Chemical High-Throughput Experimentation To Address Challenging Problems in Pharmaceutical Synthesis.

    Science.gov (United States)

    Krska, Shane W; DiRocco, Daniel A; Dreher, Spencer D; Shevlin, Michael

    2017-12-19

    The structural complexity of pharmaceuticals presents a significant challenge to modern catalysis. Many published methods that work well on simple substrates often fail when attempts are made to apply them to complex drug intermediates. The use of high-throughput experimentation (HTE) techniques offers a means to overcome this fundamental challenge by facilitating the rational exploration of large arrays of catalysts and reaction conditions in a time- and material-efficient manner. Initial forays into the use of HTE in our laboratories for solving chemistry problems centered around screening of chiral precious-metal catalysts for homogeneous asymmetric hydrogenation. The success of these early efforts in developing efficient catalytic steps for late-stage development programs motivated the desire to increase the scope of this approach to encompass other high-value catalytic chemistries. Doing so, however, required significant advances in reactor and workflow design and automation to enable the effective assembly and agitation of arrays of heterogeneous reaction mixtures and retention of volatile solvents under a wide range of temperatures. Associated innovations in high-throughput analytical chemistry techniques greatly increased the efficiency and reliability of these methods. These evolved HTE techniques have been utilized extensively to develop highly innovative catalysis solutions to the most challenging problems in large-scale pharmaceutical synthesis. Starting with Pd- and Cu-catalyzed cross-coupling chemistry, subsequent efforts expanded to other valuable modern synthetic transformations such as chiral phase-transfer catalysis, photoredox catalysis, and C-H functionalization. As our experience and confidence in HTE techniques matured, we envisioned their application beyond problems in process chemistry to address the needs of medicinal chemists. Here the problem of reaction generality is felt most acutely, and HTE approaches should prove broadly enabling

  14. A multi-endpoint, high-throughput study of nanomaterial toxicity in Caenorhabditis elegans

    Science.gov (United States)

    Jung, Sang-Kyu; Qu, Xiaolei; Aleman-Meza, Boanerges; Wang, Tianxiao; Riepe, Celeste; Liu, Zheng; Li, Qilin; Zhong, Weiwei

    2015-01-01

    The booming nanotech industry has raised public concerns about the environmental health and safety impact of engineered nanomaterials (ENMs). High-throughput assays are needed to obtain toxicity data for the rapidly increasing number of ENMs. Here we present a suite of high-throughput methods to study nanotoxicity in intact animals using Caenorhabditis elegans as a model. At the population level, our system measures food consumption of thousands of animals to evaluate population fitness. At the organism level, our automated system analyzes hundreds of individual animals for body length, locomotion speed, and lifespan. To demonstrate the utility of our system, we applied this technology to test the toxicity of 20 nanomaterials under four concentrations. Only fullerene nanoparticles (nC60), fullerol, TiO2, and CeO2 showed little or no toxicity. Various degrees of toxicity were detected from different forms of carbon nanotubes, graphene, carbon black, Ag, and fumed SiO2 nanoparticles. Aminofullerene and UV irradiated nC60 also showed small but significant toxicity. We further investigated the effects of nanomaterial size, shape, surface chemistry, and exposure conditions on toxicity. Our data are publicly available at the open-access nanotoxicity database www.QuantWorm.org/nano. PMID:25611253

  15. Learning Quantum Chemistry via a Visual-Conceptual Approach: Students' Bidirectional Textual and Visual Understanding

    Science.gov (United States)

    Dangur, Vered; Avargil, Shirly; Peskin, Uri; Dori, Yehudit Judy

    2014-01-01

    Most undergraduate chemistry courses and a few high school honors courses, which focus on physical chemistry and quantum mechanics, are highly mathematically-oriented. At the Technion, Israel Institute of Technology, we developed a new module for high school students, titled "Chemistry--From 'the Hole' to 'the Whole': From the Nanoscale to…

  16. Students' Levels of Explanations, Models, and Misconceptions in Basic Quantum Chemistry: A Phenomenographic Study

    Science.gov (United States)

    Stefani, Christina; Tsaparlis, Georgios

    2009-01-01

    We investigated students' knowledge constructions of basic quantum chemistry concepts, namely atomic orbitals, the Schrodinger equation, molecular orbitals, hybridization, and chemical bonding. Ausubel's theory of meaningful learning provided the theoretical framework and phenomenography the method of analysis. The semi-structured interview with…

  17. High Throughput Synthesis and Screening for Agents Inhibiting Androgen Receptor Mediated Gene Transcription

    National Research Council Canada - National Science Library

    Boger, Dale L

    2005-01-01

    .... This entails the high throughput synthesis of DNA binding agents related to distamycin, their screening for binding to androgen response elements using a new high throughput DNA binding screen...

  18. High Throughput Synthesis and Screening for Agents Inhibiting Androgen Receptor Mediated Gene Transcription

    National Research Council Canada - National Science Library

    Boger, Dale

    2004-01-01

    .... This entails the high throughput synthesis of DNA binding agents related to distamycin, their screening for binding to androgen response elements using a new high throughput DNA binding screen...

  19. Controlling high-throughput manufacturing at the nano-scale

    Science.gov (United States)

    Cooper, Khershed P.

    2013-09-01

    Interest in nano-scale manufacturing research and development is growing. The reason is to accelerate the translation of discoveries and inventions of nanoscience and nanotechnology into products that would benefit industry, economy and society. Ongoing research in nanomanufacturing is focused primarily on developing novel nanofabrication techniques for a variety of applications—materials, energy, electronics, photonics, biomedical, etc. Our goal is to foster the development of high-throughput methods of fabricating nano-enabled products. Large-area parallel processing and highspeed continuous processing are high-throughput means for mass production. An example of large-area processing is step-and-repeat nanoimprinting, by which nanostructures are reproduced again and again over a large area, such as a 12 in wafer. Roll-to-roll processing is an example of continuous processing, by which it is possible to print and imprint multi-level nanostructures and nanodevices on a moving flexible substrate. The big pay-off is high-volume production and low unit cost. However, the anticipated cost benefits can only be realized if the increased production rate is accompanied by high yields of high quality products. To ensure product quality, we need to design and construct manufacturing systems such that the processes can be closely monitored and controlled. One approach is to bring cyber-physical systems (CPS) concepts to nanomanufacturing. CPS involves the control of a physical system such as manufacturing through modeling, computation, communication and control. Such a closely coupled system will involve in-situ metrology and closed-loop control of the physical processes guided by physics-based models and driven by appropriate instrumentation, sensing and actuation. This paper will discuss these ideas in the context of controlling high-throughput manufacturing at the nano-scale.

  20. High-throughput screening to enhance oncolytic virus immunotherapy

    Directory of Open Access Journals (Sweden)

    Allan KJ

    2016-04-01

    Full Text Available KJ Allan,1,2 David F Stojdl,1–3 SL Swift1 1Children’s Hospital of Eastern Ontario (CHEO Research Institute, 2Department of Biology, Microbiology and Immunology, 3Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada Abstract: High-throughput screens can rapidly scan and capture large amounts of information across multiple biological parameters. Although many screens have been designed to uncover potential new therapeutic targets capable of crippling viruses that cause disease, there have been relatively few directed at improving the efficacy of viruses that are used to treat disease. Oncolytic viruses (OVs are biotherapeutic agents with an inherent specificity for treating malignant disease. Certain OV platforms – including those based on herpes simplex virus, reovirus, and vaccinia virus – have shown success against solid tumors in advanced clinical trials. Yet, many of these OVs have only undergone minimal engineering to solidify tumor specificity, with few extra modifications to manipulate additional factors. Several aspects of the interaction between an OV and a tumor-bearing host have clear value as targets to improve therapeutic outcomes. At the virus level, these include delivery to the tumor, infectivity, productivity, oncolysis, bystander killing, spread, and persistence. At the host level, these include engaging the immune system and manipulating the tumor microenvironment. Here, we review the chemical- and genome-based high-throughput screens that have been performed to manipulate such parameters during OV infection and analyze their impact on therapeutic efficacy. We further explore emerging themes that represent key areas of focus for future research. Keywords: oncolytic, virus, screen, high-throughput, cancer, chemical, genomic, immunotherapy

  1. Big Data Meets Quantum Chemistry Approximations: The Δ-Machine Learning Approach.

    Science.gov (United States)

    Ramakrishnan, Raghunathan; Dral, Pavlo O; Rupp, Matthias; von Lilienfeld, O Anatole

    2015-05-12

    Chemically accurate and comprehensive studies of the virtual space of all possible molecules are severely limited by the computational cost of quantum chemistry. We introduce a composite strategy that adds machine learning corrections to computationally inexpensive approximate legacy quantum methods. After training, highly accurate predictions of enthalpies, free energies, entropies, and electron correlation energies are possible, for significantly larger molecular sets than used for training. For thermochemical properties of up to 16k isomers of C7H10O2 we present numerical evidence that chemical accuracy can be reached. We also predict electron correlation energy in post Hartree-Fock methods, at the computational cost of Hartree-Fock, and we establish a qualitative relationship between molecular entropy and electron correlation. The transferability of our approach is demonstrated, using semiempirical quantum chemistry and machine learning models trained on 1 and 10% of 134k organic molecules, to reproduce enthalpies of all remaining molecules at density functional theory level of accuracy.

  2. High-throughput anisotropic plasma etching of polyimide for MEMS

    International Nuclear Information System (INIS)

    Bliznetsov, Vladimir; Manickam, Anbumalar; Ranganathan, Nagarajan; Chen, Junwei

    2011-01-01

    This note describes a new high-throughput process of polyimide etching for the fabrication of MEMS devices with an organic sacrificial layer approach. Using dual frequency superimposed capacitively coupled plasma we achieved a vertical profile of polyimide with an etching rate as high as 3.5 µm min −1 . After the fabrication of vertical structures in a polyimide material, additional steps were performed to fabricate structural elements of MEMS by deposition of a SiO 2 layer and performing release etching of polyimide. (technical note)

  3. Application of high-throughput DNA sequencing in phytopathology.

    Science.gov (United States)

    Studholme, David J; Glover, Rachel H; Boonham, Neil

    2011-01-01

    The new sequencing technologies are already making a big impact in academic research on medically important microbes and may soon revolutionize diagnostics, epidemiology, and infection control. Plant pathology also stands to gain from exploiting these opportunities. This manuscript reviews some applications of these high-throughput sequencing methods that are relevant to phytopathology, with emphasis on the associated computational and bioinformatics challenges and their solutions. Second-generation sequencing technologies have recently been exploited in genomics of both prokaryotic and eukaryotic plant pathogens. They are also proving to be useful in diagnostics, especially with respect to viruses. Copyright © 2011 by Annual Reviews. All rights reserved.

  4. High throughput production of mouse monoclonal antibodies using antigen microarrays

    DEFF Research Database (Denmark)

    De Masi, Federico; Chiarella, P.; Wilhelm, H.

    2005-01-01

    Recent advances in proteomics research underscore the increasing need for high-affinity monoclonal antibodies, which are still generated with lengthy, low-throughput antibody production techniques. Here we present a semi-automated, high-throughput method of hybridoma generation and identification....... Monoclonal antibodies were raised to different targets in single batch runs of 6-10 wk using multiplexed immunisations, automated fusion and cell-culture, and a novel antigen-coated microarray-screening assay. In a large-scale experiment, where eight mice were immunized with ten antigens each, we generated...

  5. REDItools: high-throughput RNA editing detection made easy.

    Science.gov (United States)

    Picardi, Ernesto; Pesole, Graziano

    2013-07-15

    The reliable detection of RNA editing sites from massive sequencing data remains challenging and, although several methodologies have been proposed, no computational tools have been released to date. Here, we introduce REDItools a suite of python scripts to perform high-throughput investigation of RNA editing using next-generation sequencing data. REDItools are in python programming language and freely available at http://code.google.com/p/reditools/. ernesto.picardi@uniba.it or graziano.pesole@uniba.it Supplementary data are available at Bioinformatics online.

  6. High Throughput System for Plant Height and Hyperspectral Measurement

    Science.gov (United States)

    Zhao, H.; Xu, L.; Jiang, H.; Shi, S.; Chen, D.

    2018-04-01

    Hyperspectral and three-dimensional measurement can obtain the intrinsic physicochemical properties and external geometrical characteristics of objects, respectively. Currently, a variety of sensors are integrated into a system to collect spectral and morphological information in agriculture. However, previous experiments were usually performed with several commercial devices on a single platform. Inadequate registration and synchronization among instruments often resulted in mismatch between spectral and 3D information of the same target. And narrow field of view (FOV) extends the working hours in farms. Therefore, we propose a high throughput prototype that combines stereo vision and grating dispersion to simultaneously acquire hyperspectral and 3D information.

  7. Quack: A quality assurance tool for high throughput sequence data.

    Science.gov (United States)

    Thrash, Adam; Arick, Mark; Peterson, Daniel G

    2018-05-01

    The quality of data generated by high-throughput DNA sequencing tools must be rapidly assessed in order to determine how useful the data may be in making biological discoveries; higher quality data leads to more confident results and conclusions. Due to the ever-increasing size of data sets and the importance of rapid quality assessment, tools that analyze sequencing data should quickly produce easily interpretable graphics. Quack addresses these issues by generating information-dense visualizations from FASTQ files at a speed far surpassing other publicly available quality assurance tools in a manner independent of sequencing technology. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Creation of a small high-throughput screening facility.

    Science.gov (United States)

    Flak, Tod

    2009-01-01

    The creation of a high-throughput screening facility within an organization is a difficult task, requiring a substantial investment of time, money, and organizational effort. Major issues to consider include the selection of equipment, the establishment of data analysis methodologies, and the formation of a group having the necessary competencies. If done properly, it is possible to build a screening system in incremental steps, adding new pieces of equipment and data analysis modules as the need grows. Based upon our experience with the creation of a small screening service, we present some guidelines to consider in planning a screening facility.

  9. High Throughput WAN Data Transfer with Hadoop-based Storage

    Science.gov (United States)

    Amin, A.; Bockelman, B.; Letts, J.; Levshina, T.; Martin, T.; Pi, H.; Sfiligoi, I.; Thomas, M.; Wüerthwein, F.

    2011-12-01

    Hadoop distributed file system (HDFS) is becoming more popular in recent years as a key building block of integrated grid storage solution in the field of scientific computing. Wide Area Network (WAN) data transfer is one of the important data operations for large high energy physics experiments to manage, share and process datasets of PetaBytes scale in a highly distributed grid computing environment. In this paper, we present the experience of high throughput WAN data transfer with HDFS-based Storage Element. Two protocols, GridFTP and fast data transfer (FDT), are used to characterize the network performance of WAN data transfer.

  10. High Throughput WAN Data Transfer with Hadoop-based Storage

    International Nuclear Information System (INIS)

    Amin, A; Thomas, M; Bockelman, B; Letts, J; Martin, T; Pi, H; Sfiligoi, I; Wüerthwein, F; Levshina, T

    2011-01-01

    Hadoop distributed file system (HDFS) is becoming more popular in recent years as a key building block of integrated grid storage solution in the field of scientific computing. Wide Area Network (WAN) data transfer is one of the important data operations for large high energy physics experiments to manage, share and process datasets of PetaBytes scale in a highly distributed grid computing environment. In this paper, we present the experience of high throughput WAN data transfer with HDFS-based Storage Element. Two protocols, GridFTP and fast data transfer (FDT), are used to characterize the network performance of WAN data transfer.

  11. High throughput platforms for structural genomics of integral membrane proteins.

    Science.gov (United States)

    Mancia, Filippo; Love, James

    2011-08-01

    Structural genomics approaches on integral membrane proteins have been postulated for over a decade, yet specific efforts are lagging years behind their soluble counterparts. Indeed, high throughput methodologies for production and characterization of prokaryotic integral membrane proteins are only now emerging, while large-scale efforts for eukaryotic ones are still in their infancy. Presented here is a review of recent literature on actively ongoing structural genomics of membrane protein initiatives, with a focus on those aimed at implementing interesting techniques aimed at increasing our rate of success for this class of macromolecules. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Spectrophotometric Enzyme Assays for High-Throughput Screening

    Directory of Open Access Journals (Sweden)

    Jean-Louis Reymond

    2004-01-01

    Full Text Available This paper reviews high-throughput screening enzyme assays developed in our laboratory over the last ten years. These enzyme assays were initially developed for the purpose of discovering catalytic antibodies by screening cell culture supernatants, but have proved generally useful for testing enzyme activities. Examples include TLC-based screening using acridone-labeled substrates, fluorogenic assays based on the β-elimination of umbelliferone or nitrophenol, and indirect assays such as the back-titration method with adrenaline and the copper-calcein fluorescence assay for aminoacids.

  13. Correction of Microplate Data from High-Throughput Screening.

    Science.gov (United States)

    Wang, Yuhong; Huang, Ruili

    2016-01-01

    High-throughput screening (HTS) makes it possible to collect cellular response data from a large number of cell lines and small molecules in a timely and cost-effective manner. The errors and noises in the microplate-formatted data from HTS have unique characteristics, and they can be generally grouped into three categories: run-wise (temporal, multiple plates), plate-wise (background pattern, single plate), and well-wise (single well). In this chapter, we describe a systematic solution for identifying and correcting such errors and noises, mainly basing on pattern recognition and digital signal processing technologies.

  14. HIGH THROUGHPUT SYSTEM FOR PLANT HEIGHT AND HYPERSPECTRAL MEASUREMENT

    Directory of Open Access Journals (Sweden)

    H. Zhao

    2018-04-01

    Full Text Available Hyperspectral and three-dimensional measurement can obtain the intrinsic physicochemical properties and external geometrical characteristics of objects, respectively. Currently, a variety of sensors are integrated into a system to collect spectral and morphological information in agriculture. However, previous experiments were usually performed with several commercial devices on a single platform. Inadequate registration and synchronization among instruments often resulted in mismatch between spectral and 3D information of the same target. And narrow field of view (FOV extends the working hours in farms. Therefore, we propose a high throughput prototype that combines stereo vision and grating dispersion to simultaneously acquire hyperspectral and 3D information.

  15. A high-throughput microtiter plate based method for the determination of peracetic acid and hydrogen peroxide.

    Science.gov (United States)

    Putt, Karson S; Pugh, Randall B

    2013-01-01

    Peracetic acid is gaining usage in numerous industries who have found a myriad of uses for its antimicrobial activity. However, rapid high throughput quantitation methods for peracetic acid and hydrogen peroxide are lacking. Herein, we describe the development of a high-throughput microtiter plate based assay based upon the well known and trusted titration chemical reactions. The adaptation of these titration chemistries to rapid plate based absorbance methods for the sequential determination of hydrogen peroxide specifically and the total amount of peroxides present in solution are described. The results of these methods were compared to those of a standard titration and found to be in good agreement. Additionally, the utility of the developed method is demonstrated through the generation of degradation curves of both peracetic acid and hydrogen peroxide in a mixed solution.

  16. A high-throughput microtiter plate based method for the determination of peracetic acid and hydrogen peroxide.

    Directory of Open Access Journals (Sweden)

    Karson S Putt

    Full Text Available Peracetic acid is gaining usage in numerous industries who have found a myriad of uses for its antimicrobial activity. However, rapid high throughput quantitation methods for peracetic acid and hydrogen peroxide are lacking. Herein, we describe the development of a high-throughput microtiter plate based assay based upon the well known and trusted titration chemical reactions. The adaptation of these titration chemistries to rapid plate based absorbance methods for the sequential determination of hydrogen peroxide specifically and the total amount of peroxides present in solution are described. The results of these methods were compared to those of a standard titration and found to be in good agreement. Additionally, the utility of the developed method is demonstrated through the generation of degradation curves of both peracetic acid and hydrogen peroxide in a mixed solution.

  17. High-Throughput Particle Manipulation Based on Hydrodynamic Effects in Microchannels

    Directory of Open Access Journals (Sweden)

    Chao Liu

    2017-03-01

    Full Text Available Microfluidic techniques are effective tools for precise manipulation of particles and cells, whose enrichment and separation is crucial for a wide range of applications in biology, medicine, and chemistry. Recently, lateral particle migration induced by the intrinsic hydrodynamic effects in microchannels, such as inertia and elasticity, has shown its promise for high-throughput and label-free particle manipulation. The particle migration can be engineered to realize the controllable focusing and separation of particles based on a difference in size. The widespread use of inertial and viscoelastic microfluidics depends on the understanding of hydrodynamic effects on particle motion. This review will summarize the progress in the fundamental mechanisms and key applications of inertial and viscoelastic particle manipulation.

  18. Development and operation of a high-throughput accurate-wavelength lens-based spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Bell, Ronald E., E-mail: rbell@pppl.gov [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543 (United States)

    2014-11-15

    A high-throughput spectrometer for the 400–820 nm wavelength range has been developed for charge exchange recombination spectroscopy or general spectroscopy. A large 2160 mm{sup −1} grating is matched with fast f/1.8 200 mm lenses, which provide stigmatic imaging. A precision optical encoder measures the grating angle with an accuracy ≤0.075 arc sec. A high quantum efficiency low-etaloning CCD detector allows operation at longer wavelengths. A patch panel allows input fibers to interface with interchangeable fiber holders that attach to a kinematic mount at the entrance slit. Computer-controlled hardware allows automated control of wavelength, timing, f-number, automated data collection, and wavelength calibration.

  19. High-throughput fragment screening by affinity LC-MS.

    Science.gov (United States)

    Duong-Thi, Minh-Dao; Bergström, Maria; Fex, Tomas; Isaksson, Roland; Ohlson, Sten

    2013-02-01

    Fragment screening, an emerging approach for hit finding in drug discovery, has recently been proven effective by its first approved drug, vemurafenib, for cancer treatment. Techniques such as nuclear magnetic resonance, surface plasmon resonance, and isothemal titration calorimetry, with their own pros and cons, have been employed for screening fragment libraries. As an alternative approach, screening based on high-performance liquid chromatography separation has been developed. In this work, we present weak affinity LC/MS as a method to screen fragments under high-throughput conditions. Affinity-based capillary columns with immobilized thrombin were used to screen a collection of 590 compounds from a fragment library. The collection was divided into 11 mixtures (each containing 35 to 65 fragments) and screened by MS detection. The primary screening was performed in 3500 fragments per day). Thirty hits were defined, which subsequently entered a secondary screening using an active site-blocked thrombin column for confirmation of specificity. One hit showed selective binding to thrombin with an estimated dissociation constant (K (D)) in the 0.1 mM range. This study shows that affinity LC/MS is characterized by high throughput, ease of operation, and low consumption of target and fragments, and therefore it promises to be a valuable method for fragment screening.

  20. High-throughput screening of ionic conductivity in polymer membranes

    International Nuclear Information System (INIS)

    Zapata, Pedro; Basak, Pratyay; Carson Meredith, J.

    2009-01-01

    Combinatorial and high-throughput techniques have been successfully used for efficient and rapid property screening in multiple fields. The use of these techniques can be an advantageous new approach to assay ionic conductivity and accelerate the development of novel materials in research areas such as fuel cells. A high-throughput ionic conductivity (HTC) apparatus is described and applied to screening candidate polymer electrolyte membranes for fuel cell applications. The device uses a miniature four-point probe for rapid, automated point-to-point AC electrochemical impedance measurements in both liquid and humid air environments. The conductivity of Nafion 112 HTC validation standards was within 1.8% of the manufacturer's specification. HTC screening of 40 novel Kynar poly(vinylidene fluoride) (PVDF)/acrylic polyelectrolyte (PE) membranes focused on varying the Kynar type (5x) and PE composition (8x) using reduced sample sizes. Two factors were found to be significant in determining the proton conducting capacity: (1) Kynar PVDF series: membranes containing a particular Kynar PVDF type exhibited statistically identical mean conductivity as other membranes containing different Kynar PVDF types that belong to the same series or family. (2) Maximum effective amount of polyelectrolyte: increments in polyelectrolyte content from 55 wt% to 60 wt% showed no statistically significant effect in increasing conductivity. In fact, some membranes experienced a reduction in conductivity.

  1. High-throughput technology for novel SO2 oxidation catalysts

    International Nuclear Information System (INIS)

    Loskyll, Jonas; Stoewe, Klaus; Maier, Wilhelm F

    2011-01-01

    We review the state of the art and explain the need for better SO 2 oxidation catalysts for the production of sulfuric acid. A high-throughput technology has been developed for the study of potential catalysts in the oxidation of SO 2 to SO 3 . High-throughput methods are reviewed and the problems encountered with their adaptation to the corrosive conditions of SO 2 oxidation are described. We show that while emissivity-corrected infrared thermography (ecIRT) can be used for primary screening, it is prone to errors because of the large variations in the emissivity of the catalyst surface. UV-visible (UV-Vis) spectrometry was selected instead as a reliable analysis method of monitoring the SO 2 conversion. Installing plain sugar absorbents at reactor outlets proved valuable for the detection and quantitative removal of SO 3 from the product gas before the UV-Vis analysis. We also overview some elements used for prescreening and those remaining after the screening of the first catalyst generations. (topical review)

  2. High-throughput electrical characterization for robust overlay lithography control

    Science.gov (United States)

    Devender, Devender; Shen, Xumin; Duggan, Mark; Singh, Sunil; Rullan, Jonathan; Choo, Jae; Mehta, Sohan; Tang, Teck Jung; Reidy, Sean; Holt, Jonathan; Kim, Hyung Woo; Fox, Robert; Sohn, D. K.

    2017-03-01

    Realizing sensitive, high throughput and robust overlay measurement is a challenge in current 14nm and advanced upcoming nodes with transition to 300mm and upcoming 450mm semiconductor manufacturing, where slight deviation in overlay has significant impact on reliability and yield1). Exponentially increasing number of critical masks in multi-patterning lithoetch, litho-etch (LELE) and subsequent LELELE semiconductor processes require even tighter overlay specification2). Here, we discuss limitations of current image- and diffraction- based overlay measurement techniques to meet these stringent processing requirements due to sensitivity, throughput and low contrast3). We demonstrate a new electrical measurement based technique where resistance is measured for a macro with intentional misalignment between two layers. Overlay is quantified by a parabolic fitting model to resistance where minima and inflection points are extracted to characterize overlay control and process window, respectively. Analyses using transmission electron microscopy show good correlation between actual overlay performance and overlay obtained from fitting. Additionally, excellent correlation of overlay from electrical measurements to existing image- and diffraction- based techniques is found. We also discuss challenges of integrating electrical measurement based approach in semiconductor manufacturing from Back End of Line (BEOL) perspective. Our findings open up a new pathway for accessing simultaneous overlay as well as process window and margins from a robust, high throughput and electrical measurement approach.

  3. Fluorescent foci quantitation for high-throughput analysis

    Directory of Open Access Journals (Sweden)

    Elena Ledesma-Fernández

    2015-06-01

    Full Text Available A number of cellular proteins localize to discrete foci within cells, for example DNA repair proteins, microtubule organizing centers, P bodies or kinetochores. It is often possible to measure the fluorescence emission from tagged proteins within these foci as a surrogate for the concentration of that specific protein. We wished to develop tools that would allow quantitation of fluorescence foci intensities in high-throughput studies. As proof of principle we have examined the kinetochore, a large multi-subunit complex that is critical for the accurate segregation of chromosomes during cell division. Kinetochore perturbations lead to aneuploidy, which is a hallmark of cancer cells. Hence, understanding kinetochore homeostasis and regulation are important for a global understanding of cell division and genome integrity. The 16 budding yeast kinetochores colocalize within the nucleus to form a single focus. Here we have created a set of freely-available tools to allow high-throughput quantitation of kinetochore foci fluorescence. We use this ‘FociQuant’ tool to compare methods of kinetochore quantitation and we show proof of principle that FociQuant can be used to identify changes in kinetochore protein levels in a mutant that affects kinetochore function. This analysis can be applied to any protein that forms discrete foci in cells.

  4. A gas trapping method for high-throughput metabolic experiments.

    Science.gov (United States)

    Krycer, James R; Diskin, Ciana; Nelson, Marin E; Zeng, Xiao-Yi; Fazakerley, Daniel J; James, David E

    2018-01-01

    Research into cellular metabolism has become more high-throughput, with typical cell-culture experiments being performed in multiwell plates (microplates). This format presents a challenge when trying to collect gaseous products, such as carbon dioxide (CO2), which requires a sealed environment and a vessel separate from the biological sample. To address this limitation, we developed a gas trapping protocol using perforated plastic lids in sealed cell-culture multiwell plates. We used this trap design to measure CO2 production from glucose and fatty acid metabolism, as well as hydrogen sulfide production from cysteine-treated cells. Our data clearly show that this gas trap can be applied to liquid and solid gas-collection media and can be used to study gaseous product generation by both adherent cells and cells in suspension. Since our gas traps can be adapted to multiwell plates of various sizes, they present a convenient, cost-effective solution that can accommodate the trend toward high-throughput measurements in metabolic research.

  5. High-throughput GPU-based LDPC decoding

    Science.gov (United States)

    Chang, Yang-Lang; Chang, Cheng-Chun; Huang, Min-Yu; Huang, Bormin

    2010-08-01

    Low-density parity-check (LDPC) code is a linear block code known to approach the Shannon limit via the iterative sum-product algorithm. LDPC codes have been adopted in most current communication systems such as DVB-S2, WiMAX, WI-FI and 10GBASE-T. LDPC for the needs of reliable and flexible communication links for a wide variety of communication standards and configurations have inspired the demand for high-performance and flexibility computing. Accordingly, finding a fast and reconfigurable developing platform for designing the high-throughput LDPC decoder has become important especially for rapidly changing communication standards and configurations. In this paper, a new graphic-processing-unit (GPU) LDPC decoding platform with the asynchronous data transfer is proposed to realize this practical implementation. Experimental results showed that the proposed GPU-based decoder achieved 271x speedup compared to its CPU-based counterpart. It can serve as a high-throughput LDPC decoder.

  6. A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay.

    Science.gov (United States)

    Todd, Douglas W; Philip, Rohit C; Niihori, Maki; Ringle, Ryan A; Coyle, Kelsey R; Zehri, Sobia F; Zabala, Leanne; Mudery, Jordan A; Francis, Ross H; Rodriguez, Jeffrey J; Jacob, Abraham

    2017-08-01

    Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells. Building on work by our group and others, we have built a new, fully automated high-throughput behavioral assay system that uses automated image analysis techniques to quantify rheotaxis behavior. This novel system consists of a custom-designed swimming apparatus and imaging system consisting of network-controlled Raspberry Pi microcomputers capturing infrared video. Automated analysis techniques detect individual zebrafish, compute their orientation, and quantify the rheotaxis behavior of a zebrafish test population, producing a powerful, high-throughput behavioral assay. Using our fully automated biological assay to test a standardized ototoxic dose of cisplatin against varying doses of compounds that protect or regenerate hair cells may facilitate rapid translation of candidate drugs into preclinical mammalian models of hearing loss.

  7. The JCSG high-throughput structural biology pipeline

    International Nuclear Information System (INIS)

    Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wooley, John; Wüthrich, Kurt; Wilson, Ian A.

    2010-01-01

    The Joint Center for Structural Genomics high-throughput structural biology pipeline has delivered more than 1000 structures to the community over the past ten years and has made a significant contribution to the overall goal of the NIH Protein Structure Initiative (PSI) of expanding structural coverage of the protein universe. The Joint Center for Structural Genomics high-throughput structural biology pipeline has delivered more than 1000 structures to the community over the past ten years. The JCSG has made a significant contribution to the overall goal of the NIH Protein Structure Initiative (PSI) of expanding structural coverage of the protein universe, as well as making substantial inroads into structural coverage of an entire organism. Targets are processed through an extensive combination of bioinformatics and biophysical analyses to efficiently characterize and optimize each target prior to selection for structure determination. The pipeline uses parallel processing methods at almost every step in the process and can adapt to a wide range of protein targets from bacterial to human. The construction, expansion and optimization of the JCSG gene-to-structure pipeline over the years have resulted in many technological and methodological advances and developments. The vast number of targets and the enormous amounts of associated data processed through the multiple stages of the experimental pipeline required the development of variety of valuable resources that, wherever feasible, have been converted to free-access web-based tools and applications

  8. High-throughput characterization for solar fuels materials discovery

    Science.gov (United States)

    Mitrovic, Slobodan; Becerra, Natalie; Cornell, Earl; Guevarra, Dan; Haber, Joel; Jin, Jian; Jones, Ryan; Kan, Kevin; Marcin, Martin; Newhouse, Paul; Soedarmadji, Edwin; Suram, Santosh; Xiang, Chengxiang; Gregoire, John; High-Throughput Experimentation Team

    2014-03-01

    In this talk I will present the status of the High-Throughput Experimentation (HTE) project of the Joint Center for Artificial Photosynthesis (JCAP). JCAP is an Energy Innovation Hub of the U.S. Department of Energy with a mandate to deliver a solar fuel generator based on an integrated photoelectrochemical cell (PEC). However, efficient and commercially viable catalysts or light absorbers for the PEC do not exist. The mission of HTE is to provide the accelerated discovery through combinatorial synthesis and rapid screening of material properties. The HTE pipeline also features high-throughput material characterization using x-ray diffraction and x-ray photoemission spectroscopy (XPS). In this talk I present the currently operating pipeline and focus on our combinatorial XPS efforts to build the largest free database of spectra from mixed-metal oxides, nitrides, sulfides and alloys. This work was performed at Joint Center for Artificial Photosynthesis, a DOE Energy Innovation Hub, supported through the Office of Science of the U.S. Department of Energy under Award No. DE-SC0004993.

  9. Combinatorial chemoenzymatic synthesis and high-throughput screening of sialosides.

    Science.gov (United States)

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

    2008-09-19

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

  10. COMPUTER APPROACHES TO WHEAT HIGH-THROUGHPUT PHENOTYPING

    Directory of Open Access Journals (Sweden)

    Afonnikov D.

    2012-08-01

    Full Text Available The growing need for rapid and accurate approaches for large-scale assessment of phenotypic characters in plants becomes more and more obvious in the studies looking into relationships between genotype and phenotype. This need is due to the advent of high throughput methods for analysis of genomes. Nowadays, any genetic experiment involves data on thousands and dozens of thousands of plants. Traditional ways of assessing most phenotypic characteristics (those with reliance on the eye, the touch, the ruler are little effective on samples of such sizes. Modern approaches seek to take advantage of automated phenotyping, which warrants a much more rapid data acquisition, higher accuracy of the assessment of phenotypic features, measurement of new parameters of these features and exclusion of human subjectivity from the process. Additionally, automation allows measurement data to be rapidly loaded into computer databases, which reduces data processing time.In this work, we present the WheatPGE information system designed to solve the problem of integration of genotypic and phenotypic data and parameters of the environment, as well as to analyze the relationships between the genotype and phenotype in wheat. The system is used to consolidate miscellaneous data on a plant for storing and processing various morphological traits and genotypes of wheat plants as well as data on various environmental factors. The system is available at www.wheatdb.org. Its potential in genetic experiments has been demonstrated in high-throughput phenotyping of wheat leaf pubescence.

  11. High-throughput screening with micro-x-ray fluorescence

    International Nuclear Information System (INIS)

    Havrilla, George J.; Miller, Thomasin C.

    2005-01-01

    Micro-x-ray fluorescence (MXRF) is a useful characterization tool for high-throughput screening of combinatorial libraries. Due to the increasing threat of use of chemical warfare (CW) agents both in military actions and against civilians by terrorist extremists, there is a strong push to improve existing methods and develop means for the detection of a broad spectrum of CW agents in a minimal amount of time to increase national security. This paper describes a combinatorial high-throughput screening technique for CW receptor discovery to aid in sensor development. MXRF can screen materials for elemental composition at the mesoscale level (tens to hundreds of micrometers). The key aspect of this work is the use of commercial MXRF instrumentation coupled with the inherent heteroatom elements within the target molecules of the combinatorial reaction to provide rapid and specific identification of lead species. The method is demonstrated by screening an 11-mer oligopeptide library for selective binding of the degradation products of the nerve agent VX. The identified oligopeptides can be used as selective molecular receptors for sensor development. The MXRF screening method is nondestructive, requires minimal sample preparation or special tags for analysis, and the screening time depends on the desired sensitivity

  12. Molecular physics and chemistry applications of quantum Monte Carlo

    International Nuclear Information System (INIS)

    Reynolds, P.J.; Barnett, R.N.; Hammond, B.L.; Lester, W.A. Jr.

    1985-09-01

    We discuss recent work with the diffusion quantum Monte Carlo (QMC) method in its application to molecular systems. The formal correspondence of the imaginary time Schroedinger equation to a diffusion equation allows one to calculate quantum mechanical expectation values as Monte Carlo averages over an ensemble of random walks. We report work on atomic and molecular total energies, as well as properties including electron affinities, binding energies, reaction barriers, and moments of the electronic charge distribution. A brief discussion is given on how standard QMC must be modified for calculating properties. Calculated energies and properties are presented for a number of molecular systems, including He, F, F - , H 2 , N, and N 2 . Recent progress in extending the basic QMC approach to the calculation of ''analytic'' (as opposed to finite-difference) derivatives of the energy is presented, together with an H 2 potential-energy curve obtained using analytic derivatives. 39 refs., 1 fig., 2 tabs

  13. High-Throughput Screening Using Fourier-Transform Infrared Imaging

    Directory of Open Access Journals (Sweden)

    Erdem Sasmaz

    2015-06-01

    Full Text Available Efficient parallel screening of combinatorial libraries is one of the most challenging aspects of the high-throughput (HT heterogeneous catalysis workflow. Today, a number of methods have been used in HT catalyst studies, including various optical, mass-spectrometry, and gas-chromatography techniques. Of these, rapid-scanning Fourier-transform infrared (FTIR imaging is one of the fastest and most versatile screening techniques. Here, the new design of the 16-channel HT reactor is presented and test results for its accuracy and reproducibility are shown. The performance of the system was evaluated through the oxidation of CO over commercial Pd/Al2O3 and cobalt oxide nanoparticles synthesized with different reducer-reductant molar ratios, surfactant types, metal and surfactant concentrations, synthesis temperatures, and ramp rates.

  14. High-Throughput Nanoindentation for Statistical and Spatial Property Determination

    Science.gov (United States)

    Hintsala, Eric D.; Hangen, Ude; Stauffer, Douglas D.

    2018-04-01

    Standard nanoindentation tests are "high throughput" compared to nearly all other mechanical tests, such as tension or compression. However, the typical rates of tens of tests per hour can be significantly improved. These higher testing rates enable otherwise impractical studies requiring several thousands of indents, such as high-resolution property mapping and detailed statistical studies. However, care must be taken to avoid systematic errors in the measurement, including choosing of the indentation depth/spacing to avoid overlap of plastic zones, pileup, and influence of neighboring microstructural features in the material being tested. Furthermore, since fast loading rates are required, the strain rate sensitivity must also be considered. A review of these effects is given, with the emphasis placed on making complimentary standard nanoindentation measurements to address these issues. Experimental applications of the technique, including mapping of welds, microstructures, and composites with varying length scales, along with studying the effect of surface roughness on nominally homogeneous specimens, will be presented.

  15. Proposed high throughput electrorefining treatment for spent N- Reactor fuel

    International Nuclear Information System (INIS)

    Gay, E.C.; Miller, W.E.; Laidler, J.J.

    1996-01-01

    A high-throughput electrorefining process is being adapted to treat spent N-Reactor fuel for ultimate disposal in a geologic repository. Anodic dissolution tests were made with unirradiated N-Reactor fuel to determine the type of fragmentation necessary to provide fuel segments suitable for this process. Based on these tests, a conceptual design was produced of a plant-scale electrorefiner. In this design, the diameter of an electrode assembly is about 1.07 m (42 in.). Three of these assemblies in an electrorefiner would accommodate a 3-metric-ton batch of N-Reactor fuel that would be processed at a rate of 42 kg of uranium per hour

  16. Printing Proteins as Microarrays for High-Throughput Function Determination

    Science.gov (United States)

    MacBeath, Gavin; Schreiber, Stuart L.

    2000-09-01

    Systematic efforts are currently under way to construct defined sets of cloned genes for high-throughput expression and purification of recombinant proteins. To facilitate subsequent studies of protein function, we have developed miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins. A high-precision robot designed to manufacture complementary DNA microarrays was used to spot proteins onto chemically derivatized glass slides at extremely high spatial densities. The proteins attached covalently to the slide surface yet retained their ability to interact specifically with other proteins, or with small molecules, in solution. Three applications for protein microarrays were demonstrated: screening for protein-protein interactions, identifying the substrates of protein kinases, and identifying the protein targets of small molecules.

  17. High-throughput determination of RNA structure by proximity ligation.

    Science.gov (United States)

    Ramani, Vijay; Qiu, Ruolan; Shendure, Jay

    2015-09-01

    We present an unbiased method to globally resolve RNA structures through pairwise contact measurements between interacting regions. RNA proximity ligation (RPL) uses proximity ligation of native RNA followed by deep sequencing to yield chimeric reads with ligation junctions in the vicinity of structurally proximate bases. We apply RPL in both baker's yeast (Saccharomyces cerevisiae) and human cells and generate contact probability maps for ribosomal and other abundant RNAs, including yeast snoRNAs, the RNA subunit of the signal recognition particle and the yeast U2 spliceosomal RNA homolog. RPL measurements correlate with established secondary structures for these RNA molecules, including stem-loop structures and long-range pseudoknots. We anticipate that RPL will complement the current repertoire of computational and experimental approaches in enabling the high-throughput determination of secondary and tertiary RNA structures.

  18. The Principals and Practice of Distributed High Throughput Computing

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    The potential of Distributed Processing Systems to deliver computing capabilities with qualities ranging from high availability and reliability to easy expansion in functionality and capacity were recognized and formalized in the 1970’s. For more three decade these principals Distributed Computing guided the development of the HTCondor resource and job management system. The widely adopted suite of software tools offered by HTCondor are based on novel distributed computing technologies and are driven by the evolving needs of High Throughput scientific applications. We will review the principals that underpin our work, the distributed computing frameworks and technologies we developed and the lessons we learned from delivering effective and dependable software tools in an ever changing landscape computing technologies and needs that range today from a desktop computer to tens of thousands of cores offered by commercial clouds. About the speaker Miron Livny received a B.Sc. degree in Physics and Mat...

  19. Noise and non-linearities in high-throughput data

    International Nuclear Information System (INIS)

    Nguyen, Viet-Anh; Lió, Pietro; Koukolíková-Nicola, Zdena; Bagnoli, Franco

    2009-01-01

    High-throughput data analyses are becoming common in biology, communications, economics and sociology. The vast amounts of data are usually represented in the form of matrices and can be considered as knowledge networks. Spectra-based approaches have proved useful in extracting hidden information within such networks and for estimating missing data, but these methods are based essentially on linear assumptions. The physical models of matching, when applicable, often suggest non-linear mechanisms, that may sometimes be identified as noise. The use of non-linear models in data analysis, however, may require the introduction of many parameters, which lowers the statistical weight of the model. According to the quality of data, a simpler linear analysis may be more convenient than more complex approaches. In this paper, we show how a simple non-parametric Bayesian model may be used to explore the role of non-linearities and noise in synthetic and experimental data sets

  20. High-throughput ab-initio dilute solute diffusion database.

    Science.gov (United States)

    Wu, Henry; Mayeshiba, Tam; Morgan, Dane

    2016-07-19

    We demonstrate automated generation of diffusion databases from high-throughput density functional theory (DFT) calculations. A total of more than 230 dilute solute diffusion systems in Mg, Al, Cu, Ni, Pd, and Pt host lattices have been determined using multi-frequency diffusion models. We apply a correction method for solute diffusion in alloys using experimental and simulated values of host self-diffusivity. We find good agreement with experimental solute diffusion data, obtaining a weighted activation barrier RMS error of 0.176 eV when excluding magnetic solutes in non-magnetic alloys. The compiled database is the largest collection of consistently calculated ab-initio solute diffusion data in the world.

  1. Dimensioning storage and computing clusters for efficient High Throughput Computing

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    Scientific experiments are producing huge amounts of data, and they continue increasing the size of their datasets and the total volume of data. These data are then processed by researchers belonging to large scientific collaborations, with the Large Hadron Collider being a good example. The focal point of Scientific Data Centres has shifted from coping efficiently with PetaByte scale storage to deliver quality data processing throughput. The dimensioning of the internal components in High Throughput Computing (HTC) data centers is of crucial importance to cope with all the activities demanded by the experiments, both the online (data acceptance) and the offline (data processing, simulation and user analysis). This requires a precise setup involving disk and tape storage services, a computing cluster and the internal networking to prevent bottlenecks, overloads and undesired slowness that lead to losses cpu cycles and batch jobs failures. In this paper we point out relevant features for running a successful s...

  2. High Throughput In Situ XAFS Screening of Catalysts

    International Nuclear Information System (INIS)

    Tsapatsaris, Nikolaos; Beesley, Angela M.; Weiher, Norbert; Tatton, Helen; Schroeder, Sven L. M.; Dent, Andy J.; Mosselmans, Frederick J. W.; Tromp, Moniek; Russu, Sergio; Evans, John; Harvey, Ian; Hayama, Shu

    2007-01-01

    We outline and demonstrate the feasibility of high-throughput (HT) in situ XAFS for synchrotron radiation studies. An XAS data acquisition and control system for the analysis of dynamic materials libraries under control of temperature and gaseous environments has been developed. The system is compatible with the 96-well industry standard and coupled to multi-stream quadrupole mass spectrometry (QMS) analysis of reactor effluents. An automated analytical workflow generates data quickly compared to traditional individual spectrum acquisition and analyses them in quasi-real time using an HT data analysis tool based on IFFEFIT. The system was used for the automated characterization of a library of 91 catalyst precursors containing ternary combinations of Cu, Pt, and Au on γ-Al2O3, and for the in situ characterization of Au catalysts supported on Al2O3 and TiO2

  3. Machine Learning for High-Throughput Stress Phenotyping in Plants.

    Science.gov (United States)

    Singh, Arti; Ganapathysubramanian, Baskar; Singh, Asheesh Kumar; Sarkar, Soumik

    2016-02-01

    Advances in automated and high-throughput imaging technologies have resulted in a deluge of high-resolution images and sensor data of plants. However, extracting patterns and features from this large corpus of data requires the use of machine learning (ML) tools to enable data assimilation and feature identification for stress phenotyping. Four stages of the decision cycle in plant stress phenotyping and plant breeding activities where different ML approaches can be deployed are (i) identification, (ii) classification, (iii) quantification, and (iv) prediction (ICQP). We provide here a comprehensive overview and user-friendly taxonomy of ML tools to enable the plant community to correctly and easily apply the appropriate ML tools and best-practice guidelines for various biotic and abiotic stress traits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. High-throughput mouse genotyping using robotics automation.

    Science.gov (United States)

    Linask, Kaari L; Lo, Cecilia W

    2005-02-01

    The use of mouse models is rapidly expanding in biomedical research. This has dictated the need for the rapid genotyping of mutant mouse colonies for more efficient utilization of animal holding space. We have established a high-throughput protocol for mouse genotyping using two robotics workstations: a liquid-handling robot to assemble PCR and a microfluidics electrophoresis robot for PCR product analysis. This dual-robotics setup incurs lower start-up costs than a fully automated system while still minimizing human intervention. Essential to this automation scheme is the construction of a database containing customized scripts for programming the robotics workstations. Using these scripts and the robotics systems, multiple combinations of genotyping reactions can be assembled simultaneously, allowing even complex genotyping data to be generated rapidly with consistency and accuracy. A detailed protocol, database, scripts, and additional background information are available at http://dir.nhlbi.nih.gov/labs/ldb-chd/autogene/.

  5. Ethoscopes: An open platform for high-throughput ethomics.

    Directory of Open Access Journals (Sweden)

    Quentin Geissmann

    2017-10-01

    Full Text Available Here, we present the use of ethoscopes, which are machines for high-throughput analysis of behavior in Drosophila and other animals. Ethoscopes provide a software and hardware solution that is reproducible and easily scalable. They perform, in real-time, tracking and profiling of behavior by using a supervised machine learning algorithm, are able to deliver behaviorally triggered stimuli to flies in a feedback-loop mode, and are highly customizable and open source. Ethoscopes can be built easily by using 3D printing technology and rely on Raspberry Pi microcomputers and Arduino boards to provide affordable and flexible hardware. All software and construction specifications are available at http://lab.gilest.ro/ethoscope.

  6. Radiation metabolomics : a window to high throughput radiation biodosimetry

    International Nuclear Information System (INIS)

    Rana, Poonam

    2016-01-01

    In the event of an intentional or accidental release of ionizing radiation in a densely populated area, timely assessment and triage of the general population for radiation exposure is critical. In particular, a significant number of victims may sustain radiation injury, which increases mortality and worsens the overall prognosis of victims from radiation trauma. Availability of a high-throughput noninvasive in vivo biodosimetry tool for assessing the radiation exposure is of particular importance for timely diagnosis of radiation injury. In this study, we describe the potential NMR techniques in evaluating the radiation injury. NMR is the most versatile technique that has been extensively used in the diverse fields of science since its discovery. NMR and biomedical sciences have been going hand in hand since its application in clinical imaging as MRI and metabolic profiling of biofluids was identified. We have established an NMR based metabonomic and in vivo spectroscopy approach to analyse and identify metabolic profile to measure metabolic fingerprint for radiation exposure. NMR spectroscopy experiments were conducted on urine and serum samples collected from mice irradiated with different doses of radiation. Additionally, in vivo NMR spectroscopy was also performed in different region of brains post irradiation in animal model. A number of metabolites associated with energy metabolism, gut flora metabolites, osmolytes, amino acids and membrane metabolism were identified in serum and urine metabolome. Our results illustrated a metabolic fingerprint for radiation exposure that elucidates perturbed physiological functions. Quantitative as well as multivariate analysis/assessment of these metabolites demonstrated dose and time dependent toxicological effect. In vivo spectroscopy from brain showed radiation induced changes in hippocampus region indicating whole body radiation had striking effect on brain metabolism as well. The results of the present work lay a

  7. A robust robotic high-throughput antibody purification platform.

    Science.gov (United States)

    Schmidt, Peter M; Abdo, Michael; Butcher, Rebecca E; Yap, Min-Yin; Scotney, Pierre D; Ramunno, Melanie L; Martin-Roussety, Genevieve; Owczarek, Catherine; Hardy, Matthew P; Chen, Chao-Guang; Fabri, Louis J

    2016-07-15

    Monoclonal antibodies (mAbs) have become the fastest growing segment in the drug market with annual sales of more than 40 billion US$ in 2013. The selection of lead candidate molecules involves the generation of large repertoires of antibodies from which to choose a final therapeutic candidate. Improvements in the ability to rapidly produce and purify many antibodies in sufficient quantities reduces the lead time for selection which ultimately impacts on the speed with which an antibody may transition through the research stage and into product development. Miniaturization and automation of chromatography using micro columns (RoboColumns(®) from Atoll GmbH) coupled to an automated liquid handling instrument (ALH; Freedom EVO(®) from Tecan) has been a successful approach to establish high throughput process development platforms. Recent advances in transient gene expression (TGE) using the high-titre Expi293F™ system have enabled recombinant mAb titres of greater than 500mg/L. These relatively high protein titres reduce the volume required to generate several milligrams of individual antibodies for initial biochemical and biological downstream assays, making TGE in the Expi293F™ system ideally suited to high throughput chromatography on an ALH. The present publication describes a novel platform for purifying Expi293F™-expressed recombinant mAbs directly from cell-free culture supernatant on a Perkin Elmer JANUS-VariSpan ALH equipped with a plate shuttle device. The purification platform allows automated 2-step purification (Protein A-desalting/size exclusion chromatography) of several hundred mAbs per week. The new robotic method can purify mAbs with high recovery (>90%) at sub-milligram level with yields of up to 2mg from 4mL of cell-free culture supernatant. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. A pocket device for high-throughput optofluidic holographic microscopy

    Science.gov (United States)

    Mandracchia, B.; Bianco, V.; Wang, Z.; Paturzo, M.; Bramanti, A.; Pioggia, G.; Ferraro, P.

    2017-06-01

    Here we introduce a compact holographic microscope embedded onboard a Lab-on-a-Chip (LoC) platform. A wavefront division interferometer is realized by writing a polymer grating onto the channel to extract a reference wave from the object wave impinging the LoC. A portion of the beam reaches the samples flowing along the channel path, carrying their information content to the recording device, while one of the diffraction orders from the grating acts as an off-axis reference wave. Polymeric micro-lenses are delivered forward the chip by Pyro-ElectroHydroDynamic (Pyro-EHD) inkjet printing techniques. Thus, all the required optical components are embedded onboard a pocket device, and fast, non-iterative, reconstruction algorithms can be used. We use our device in combination with a novel high-throughput technique, named Space-Time Digital Holography (STDH). STDH exploits the samples motion inside microfluidic channels to obtain a synthetic hologram, mapped in a hybrid space-time domain, and with intrinsic useful features. Indeed, a single Linear Sensor Array (LSA) is sufficient to build up a synthetic representation of the entire experiment (i.e. the STDH) with unlimited Field of View (FoV) along the scanning direction, independently from the magnification factor. The throughput of the imaging system is dramatically increased as STDH provides unlimited FoV, refocusable imaging of samples inside the liquid volume with no need for hologram stitching. To test our embedded STDH microscopy module, we counted, imaged and tracked in 3D with high-throughput red blood cells moving inside the channel volume under non ideal flow conditions.

  9. A high throughput mechanical screening device for cartilage tissue engineering.

    Science.gov (United States)

    Mohanraj, Bhavana; Hou, Chieh; Meloni, Gregory R; Cosgrove, Brian D; Dodge, George R; Mauck, Robert L

    2014-06-27

    Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome, given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying 'hits', or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput. © 2013 Published by Elsevier Ltd.

  10. A High-Throughput Antibody-Based Microarray Typing Platform

    Directory of Open Access Journals (Sweden)

    Ashan Perera

    2013-05-01

    Full Text Available Many rapid methods have been developed for screening foods for the presence of pathogenic microorganisms. Rapid methods that have the additional ability to identify microorganisms via multiplexed immunological recognition have the potential for classification or typing of microbial contaminants thus facilitating epidemiological investigations that aim to identify outbreaks and trace back the contamination to its source. This manuscript introduces a novel, high throughput typing platform that employs microarrayed multiwell plate substrates and laser-induced fluorescence of the nucleic acid intercalating dye/stain SYBR Gold for detection of antibody-captured bacteria. The aim of this study was to use this platform for comparison of different sets of antibodies raised against the same pathogens as well as demonstrate its potential effectiveness for serotyping. To that end, two sets of antibodies raised against each of the “Big Six” non-O157 Shiga toxin-producing E. coli (STEC as well as E. coli O157:H7 were array-printed into microtiter plates, and serial dilutions of the bacteria were added and subsequently detected. Though antibody specificity was not sufficient for the development of an STEC serotyping method, the STEC antibody sets performed reasonably well exhibiting that specificity increased at lower capture antibody concentrations or, conversely, at lower bacterial target concentrations. The favorable results indicated that with sufficiently selective and ideally concentrated sets of biorecognition elements (e.g., antibodies or aptamers, this high-throughput platform can be used to rapidly type microbial isolates derived from food samples within ca. 80 min of total assay time. It can also potentially be used to detect the pathogens from food enrichments and at least serve as a platform for testing antibodies.

  11. A Primer on High-Throughput Computing for Genomic Selection

    Directory of Open Access Journals (Sweden)

    Xiao-Lin eWu

    2011-02-01

    Full Text Available High-throughput computing (HTC uses computer clusters to solve advanced computational problems, with the goal of accomplishing high throughput over relatively long periods of time. In genomic selection, for example, a set of markers covering the entire genome is used to train a model based on known data, and the resulting model is used to predict the genetic merit of selection candidates. Sophisticated models are very computationally demanding and, with several traits to be evaluated sequentially, computing time is long and output is low. In this paper, we present scenarios and basic principles of how HTC can be used in genomic selection, implemented using various techniques from simple batch processing to pipelining in distributed computer clusters. Various scripting languages, such as shell scripting, Perl and R, are also very useful to devise pipelines. By pipelining, we can reduce total computing time and consequently increase throughput. In comparison to the traditional data processing pipeline residing on the central processors, performing general purpose computation on a graphics processing unit (GPU provide a new-generation approach to massive parallel computing in genomic selection. While the concept of HTC may still be new to many researchers in animal breeding, plant breeding, and genetics, HTC infrastructures have already been built in many institutions, such as the University of Wisconsin – Madison, which can be leveraged for genomic selection, in terms of central processing unit (CPU capacity, network connectivity, storage availability, and middleware connectivity. Exploring existing HTC infrastructures as well as general purpose computing environments will further expand our capability to meet increasing computing demands posed by unprecedented genomic data that we have today. We anticipate that HTC will impact genomic selection via better statistical models, faster solutions, and more competitive products (e.g., from design of

  12. 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.

  13. Determination of Quantum Chemistry Based Force Fields for Molecular Dynamics Simulations of Aromatic Polymers

    Science.gov (United States)

    Jaffe, Richard; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    Ab initio quantum chemistry calculations for model molecules can be used to parameterize force fields for molecular dynamics simulations of polymers. Emphasis in our research group is on using quantum chemistry-based force fields for molecular dynamics simulations of organic polymers in the melt and glassy states, but the methodology is applicable to simulations of small molecules, multicomponent systems and solutions. Special attention is paid to deriving reliable descriptions of the non-bonded and electrostatic interactions. Several procedures have been developed for deriving and calibrating these parameters. Our force fields for aromatic polyimide simulations will be described. In this application, the intermolecular interactions are the critical factor in determining many properties of the polymer (including its color).

  14. Quantum Chemistry of Solids The LCAO First Principles Treatment of Crystals

    CERN Document Server

    Evarestov, Robert A

    2007-01-01

    Quantum Chemistry of Solids delivers a comprehensive account of the main features and possibilities of LCAO methods for the first principles calculations of electronic structure of periodic systems. The first part describes the basic theory underlying the LCAO methods applied to periodic systems and the use of wave-function-based (Hartree-Fock), density-based (DFT) and hybrid hamiltonians. The translation and site symmetry consideration is included to establish connection between k-space solid-state physics and real-space quantum chemistry methods in the framework of cyclic model of an infinite crystal. The inclusion of electron correlation effects for periodic systems is considered on the basis of localized crystalline orbitals. The possibilities of LCAO methods for chemical bonding analysis in periodic systems are discussed. The second part deals with the applications of LCAO methods for calculations of bulk crystal properties, including magnetic ordering and crystal structure optimization. The discussion o...

  15. Multi-level meta-workflows: new concept for regularly occurring tasks in quantum chemistry.

    Science.gov (United States)

    Arshad, Junaid; Hoffmann, Alexander; Gesing, Sandra; Grunzke, Richard; Krüger, Jens; Kiss, Tamas; Herres-Pawlis, Sonja; Terstyanszky, Gabor

    2016-01-01

    In Quantum Chemistry, many tasks are reoccurring frequently, e.g. geometry optimizations, benchmarking series etc. Here, workflows can help to reduce the time of manual job definition and output extraction. These workflows are executed on computing infrastructures and may require large computing and data resources. Scientific workflows hide these infrastructures and the resources needed to run them. It requires significant efforts and specific expertise to design, implement and test these workflows. Many of these workflows are complex and monolithic entities that can be used for particular scientific experiments. Hence, their modification is not straightforward and it makes almost impossible to share them. To address these issues we propose developing atomic workflows and embedding them in meta-workflows. Atomic workflows deliver a well-defined research domain specific function. Publishing workflows in repositories enables workflow sharing inside and/or among scientific communities. We formally specify atomic and meta-workflows in order to define data structures to be used in repositories for uploading and sharing them. Additionally, we present a formal description focused at orchestration of atomic workflows into meta-workflows. We investigated the operations that represent basic functionalities in Quantum Chemistry, developed the relevant atomic workflows and combined them into meta-workflows. Having these workflows we defined the structure of the Quantum Chemistry workflow library and uploaded these workflows in the SHIWA Workflow Repository.Graphical AbstractMeta-workflows and embedded workflows in the template representation.

  16. Automatic Differentiation in Quantum Chemistry with Applications to Fully Variational Hartree-Fock.

    Science.gov (United States)

    Tamayo-Mendoza, Teresa; Kreisbeck, Christoph; Lindh, Roland; Aspuru-Guzik, Alán

    2018-05-23

    Automatic differentiation (AD) is a powerful tool that allows calculating derivatives of implemented algorithms with respect to all of their parameters up to machine precision, without the need to explicitly add any additional functions. Thus, AD has great potential in quantum chemistry, where gradients are omnipresent but also difficult to obtain, and researchers typically spend a considerable amount of time finding suitable analytical forms when implementing derivatives. Here, we demonstrate that AD can be used to compute gradients with respect to any parameter throughout a complete quantum chemistry method. We present DiffiQult , a Hartree-Fock implementation, entirely differentiated with the use of AD tools. DiffiQult is a software package written in plain Python with minimal deviation from standard code which illustrates the capability of AD to save human effort and time in implementations of exact gradients in quantum chemistry. We leverage the obtained gradients to optimize the parameters of one-particle basis sets in the context of the floating Gaussian framework.

  17. Quantum chemistry of the minimal CdSe clusters

    Science.gov (United States)

    Yang, Ping; Tretiak, Sergei; Masunov, Artëm E.; Ivanov, Sergei

    2008-08-01

    Colloidal quantum dots are semiconductor nanocrystals (NCs) which have stimulated a great deal of research and have attracted technical interest in recent years due to their chemical stability and the tunability of photophysical properties. While internal structure of large quantum dots is similar to bulk, their surface structure and passivating role of capping ligands (surfactants) are not fully understood to date. We apply ab initio wavefunction methods, density functional theory, and semiempirical approaches to study the passivation effects of substituted phosphine and amine ligands on the minimal cluster Cd2Se2, which is also used to benchmark different computational methods versus high level ab initio techniques. Full geometry optimization of Cd2Se2 at different theory levels and ligand coverage is used to understand the affinities of various ligands and the impact of ligands on cluster structure. Most possible bonding patterns between ligands and surface Cd/Se atoms are considered, including a ligand coordinated to Se atoms. The degree of passivation of Cd and Se atoms (one or two ligands attached to one atom) is also studied. The results suggest that B3LYP/LANL2DZ level of theory is appropriate for the system modeling, whereas frequently used semiempirical methods (such as AM1 and PM3) produce unphysical results. The use of hydrogen atom for modeling of the cluster passivating ligands is found to yield unphysical results as well. Hence, the surface termination of II-VI semiconductor NCs with hydrogen atoms often used in computational models should probably be avoided. Basis set superposition error, zero-point energy, and thermal corrections, as well as solvent effects simulated with polarized continuum model are found to produce minor variations on the ligand binding energies. The effects of Cd-Se complex structure on both the electronic band gap (highest occupied molecular orbital-lowest unoccupied molecular orbital energy difference) and ligand binding

  18. Photodissociation of quantum state-selected diatomic molecules yields new insight into ultracold chemistry

    Science.gov (United States)

    McDonald, Mickey; McGuyer, Bart H.; Lee, Chih-Hsi; Apfelbeck, Florian; Zelevinsky, Tanya

    2016-05-01

    When a molecule is subjected to a sufficiently energetic photon it can break apart into fragments through a process called ``photodissociation''. For over 70 years this simple chemical reaction has served as a vital experimental tool for acquiring information about molecular structure, since the character of the photodissociative transition can be inferred by measuring the 3D photofragment angular distribution (PAD). While theoretical understanding of this process has gradually evolved from classical considerations to a fully quantum approach, experiments to date have not yet revealed the full quantum nature of this process. In my talk I will describe recent experiments involving the photodissociation of ultracold, optical lattice-trapped, and fully quantum state-resolved 88Sr2 molecules. Optical absorption images of the PADs produced in these experiments reveal features which are inherently quantum mechanical in nature, such as matter-wave interference between output channels, and are sensitive to the quantum statistics of the molecular wavefunctions. The results of these experiments cannot be predicted using quasiclassical methods. Instead, we describe our results with a fully quantum mechanical model yielding new intuition about ultracold chemistry.

  19. Development of a High-Throughput Screen for Inhibitors of Epstein-Barr Virus EBNA1

    Science.gov (United States)

    Thompson, Scott; Messick, Troy; Schultz, David C.; Reichman, Melvin; Lieberman, Paul M.

    2012-01-01

    Latent infection with Epstein-Barr Virus (EBV) is a carcinogenic cofactor in several lymphoid and epithelial cell malignancies. At present, there are no small molecule inhibitors that specifically target EBV latent infection or latency-associated oncoproteins. EBNA1 is an EBV-encoded sequence-specific DNA-binding protein that is consistently expressed in EBV-associated tumors and required for stable maintenance of the viral genome in proliferating cells. EBNA1 is also thought to provide cell survival function in latently infected cells. In this work we describe the development of a biochemical high-throughput screening (HTS) method using a homogenous fluorescence polarization (FP) assay monitoring EBNA1 binding to its cognate DNA binding site. An FP-based counterscreen was developed using another EBV-encoded DNA binding protein, Zta, and its cognate DNA binding site. We demonstrate that EBNA1 binding to a fluorescent labeled DNA probe provides a robust assay with a Z-factor consistently greater than 0.6. A pilot screen of a small molecule library of ~14,000 compounds identified 3 structurally related molecules that selectively inhibit EBNA1, but not Zta. All three compounds had activity in a cell-based assay specific for the disruption of EBNA1 transcription repression function. One of the compounds was effective in reducing EBV genome copy number in Raji Burkitt lymphoma cells. These experiments provide a proof-of-concept that small molecule inhibitors of EBNA1 can be identified by biochemical high-throughput screening of compound libraries. Further screening in conjunction with medicinal chemistry optimization may provide a selective inhibitor of EBNA1 and EBV latent infection. PMID:20930215

  20. Crystal density predictions for nitramines based on quantum chemistry

    International Nuclear Information System (INIS)

    Qiu Ling; Xiao Heming; Gong Xuedong; Ju Xuehai; Zhu Weihua

    2007-01-01

    An efficient and convenient method for predicting the crystalline densities of energetic materials was established based on the quantum chemical computations. Density functional theory (DFT) with four different basis sets (6-31G**, 6-311G**, 6-31+G**, and 6-311++G**) and various semiempirical molecular orbital (MO) methods have been employed to predict the molecular volumes and densities of a series of energetic nitramines including acyclic, monocyclic, and polycyclic/cage molecules. The relationships between the calculated values and experimental data were discussed in detail, and linear correlations were suggested and compared at different levels. The calculation shows that if the selected basis set is larger, it will expend more CPU (central processing unit) time, larger molecular volume and smaller density will be obtained. And the densities predicted by the semiempirical MO methods are all systematically larger than the experimental data. In comparison with other methods, B3LYP/6-31G** is most accurate and economical to predict the solid-state densities of energetic nitramines. This may be instructive to the molecular designing and screening novel HEDMs

  1. On the applicability of one- and many-electron quantum chemistry models for hydrated electron clusters

    Science.gov (United States)

    Turi, László

    2016-04-01

    We evaluate the applicability of a hierarchy of quantum models in characterizing the binding energy of excess electrons to water clusters. In particular, we calculate the vertical detachment energy of an excess electron from water cluster anions with methods that include one-electron pseudopotential calculations, density functional theory (DFT) based calculations, and ab initio quantum chemistry using MP2 and eom-EA-CCSD levels of theory. The examined clusters range from the smallest cluster size (n = 2) up to nearly nanosize clusters with n = 1000 molecules. The examined cluster configurations are extracted from mixed quantum-classical molecular dynamics trajectories of cluster anions with n = 1000 water molecules using two different one-electron pseudopotenial models. We find that while MP2 calculations with large diffuse basis set provide a reasonable description for the hydrated electron system, DFT methods should be used with precaution and only after careful benchmarking. Strictly tested one-electron psudopotentials can still be considered as reasonable alternatives to DFT methods, especially in large systems. The results of quantum chemistry calculations performed on configurations, that represent possible excess electron binding motifs in the clusters, appear to be consistent with the results using a cavity structure preferring one-electron pseudopotential for the hydrated electron, while they are in sharp disagreement with the structural predictions of a non-cavity model.

  2. On the applicability of one- and many-electron quantum chemistry models for hydrated electron clusters

    Energy Technology Data Exchange (ETDEWEB)

    Turi, László, E-mail: turi@chem.elte.hu [Department of Physical Chemistry, Eötvös Loránd University, P.O. Box 32, H-1518 Budapest 112 (Hungary)

    2016-04-21

    We evaluate the applicability of a hierarchy of quantum models in characterizing the binding energy of excess electrons to water clusters. In particular, we calculate the vertical detachment energy of an excess electron from water cluster anions with methods that include one-electron pseudopotential calculations, density functional theory (DFT) based calculations, and ab initio quantum chemistry using MP2 and eom-EA-CCSD levels of theory. The examined clusters range from the smallest cluster size (n = 2) up to nearly nanosize clusters with n = 1000 molecules. The examined cluster configurations are extracted from mixed quantum-classical molecular dynamics trajectories of cluster anions with n = 1000 water molecules using two different one-electron pseudopotenial models. We find that while MP2 calculations with large diffuse basis set provide a reasonable description for the hydrated electron system, DFT methods should be used with precaution and only after careful benchmarking. Strictly tested one-electron psudopotentials can still be considered as reasonable alternatives to DFT methods, especially in large systems. The results of quantum chemistry calculations performed on configurations, that represent possible excess electron binding motifs in the clusters, appear to be consistent with the results using a cavity structure preferring one-electron pseudopotential for the hydrated electron, while they are in sharp disagreement with the structural predictions of a non-cavity model.

  3. The molecular electron density distribution meeting place of X-ray diffraction and quantum chemistry intermediate - between theory and experiment

    NARCIS (Netherlands)

    Feil, D.; Feil, Dirk

    1992-01-01

    Quantum chemistry and the concepts used daily in chemistry are increasingly growing apart. Among the concepts that are able to bridge the gap between theory and experimental practice, electron density distribution has an important place. The study of this distribution has led to new developments in

  4. Adaptation of quantum chemistry software for the electronic structure calculations on GPU for solid-state systems

    International Nuclear Information System (INIS)

    Gusakov, V.E.; Bel'ko, V.I.; Dorozhkin, N.N.

    2015-01-01

    We report on adaptation of quantum chemistry software - Quantum Espresso and LASTO - for the electronic structure calculations for the complex solid-state systems on the GeForce series GPUs using the nVIDIA CUDA technology. Specifically, protective covering based on transition metal nitrides are considered. (authors)

  5. The use of quantum chemistry in pharmaceutical research as illustrated by case studies of indometacin and carbamazepine

    DEFF Research Database (Denmark)

    Gordon, Keith C; McGoverin, Cushla M; Strachan, Clare J

    2007-01-01

    A number of case studies that illustrate how quantum chemistry may be used in studying pharmaceutical systems are reviewed. A brief introduction to quantum methods is provided and the use of these methods in understanding the structure and properties of indometacin and carbamazepine is discussed...

  6. Quantitative high throughput analytics to support polysaccharide production process development.

    Science.gov (United States)

    Noyes, Aaron; Godavarti, Ranga; Titchener-Hooker, Nigel; Coffman, Jonathan; Mukhopadhyay, Tarit

    2014-05-19

    The rapid development of purification processes for polysaccharide vaccines is constrained by a lack of analytical tools current technologies for the measurement of polysaccharide recovery and process-related impurity clearance are complex, time-consuming, and generally not amenable to high throughput process development (HTPD). HTPD is envisioned to be central to the improvement of existing polysaccharide manufacturing processes through the identification of critical process parameters that potentially impact the quality attributes of the vaccine and to the development of de novo processes for clinical candidates, across the spectrum of downstream processing. The availability of a fast and automated analytics platform will expand the scope, robustness, and evolution of Design of Experiment (DOE) studies. This paper details recent advances in improving the speed, throughput, and success of in-process analytics at the micro-scale. Two methods, based on modifications of existing procedures, are described for the rapid measurement of polysaccharide titre in microplates without the need for heating steps. A simplification of a commercial endotoxin assay is also described that features a single measurement at room temperature. These assays, along with existing assays for protein and nucleic acids are qualified for deployment in the high throughput screening of polysaccharide feedstreams. Assay accuracy, precision, robustness, interference, and ease of use are assessed and described. In combination, these assays are capable of measuring the product concentration and impurity profile of a microplate of 96 samples in less than one day. This body of work relies on the evaluation of a combination of commercially available and clinically relevant polysaccharides to ensure maximum versatility and reactivity of the final assay suite. Together, these advancements reduce overall process time by up to 30-fold and significantly reduce sample volume over current practices. The

  7. A primer on high-throughput computing for genomic selection.

    Science.gov (United States)

    Wu, Xiao-Lin; Beissinger, Timothy M; Bauck, Stewart; Woodward, Brent; Rosa, Guilherme J M; Weigel, Kent A; Gatti, Natalia de Leon; Gianola, Daniel

    2011-01-01

    High-throughput computing (HTC) uses computer clusters to solve advanced computational problems, with the goal of accomplishing high-throughput over relatively long periods of time. In genomic selection, for example, a set of markers covering the entire genome is used to train a model based on known data, and the resulting model is used to predict the genetic merit of selection candidates. Sophisticated models are very computationally demanding and, with several traits to be evaluated sequentially, computing time is long, and output is low. In this paper, we present scenarios and basic principles of how HTC can be used in genomic selection, implemented using various techniques from simple batch processing to pipelining in distributed computer clusters. Various scripting languages, such as shell scripting, Perl, and R, are also very useful to devise pipelines. By pipelining, we can reduce total computing time and consequently increase throughput. In comparison to the traditional data processing pipeline residing on the central processors, performing general-purpose computation on a graphics processing unit provide a new-generation approach to massive parallel computing in genomic selection. While the concept of HTC may still be new to many researchers in animal breeding, plant breeding, and genetics, HTC infrastructures have already been built in many institutions, such as the University of Wisconsin-Madison, which can be leveraged for genomic selection, in terms of central processing unit capacity, network connectivity, storage availability, and middleware connectivity. Exploring existing HTC infrastructures as well as general-purpose computing environments will further expand our capability to meet increasing computing demands posed by unprecedented genomic data that we have today. We anticipate that HTC will impact genomic selection via better statistical models, faster solutions, and more competitive products (e.g., from design of marker panels to realized

  8. SNP-PHAGE – High throughput SNP discovery pipeline

    Directory of Open Access Journals (Sweden)

    Cregan Perry B

    2006-10-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs as defined here are single base sequence changes or short insertion/deletions between or within individuals of a given species. As a result of their abundance and the availability of high throughput analysis technologies SNP markers have begun to replace other traditional markers such as restriction fragment length polymorphisms (RFLPs, amplified fragment length polymorphisms (AFLPs and simple sequence repeats (SSRs or microsatellite markers for fine mapping and association studies in several species. For SNP discovery from chromatogram data, several bioinformatics programs have to be combined to generate an analysis pipeline. Results have to be stored in a relational database to facilitate interrogation through queries or to generate data for further analyses such as determination of linkage disequilibrium and identification of common haplotypes. Although these tasks are routinely performed by several groups, an integrated open source SNP discovery pipeline that can be easily adapted by new groups interested in SNP marker development is currently unavailable. Results We developed SNP-PHAGE (SNP discovery Pipeline with additional features for identification of common haplotypes within a sequence tagged site (Haplotype Analysis and GenBank (-dbSNP submissions. This tool was applied for analyzing sequence traces from diverse soybean genotypes to discover over 10,000 SNPs. This package was developed on UNIX/Linux platform, written in Perl and uses a MySQL database. Scripts to generate a user-friendly web interface are also provided with common queries for preliminary data analysis. A machine learning tool developed by this group for increasing the efficiency of SNP discovery is integrated as a part of this package as an optional feature. The SNP-PHAGE package is being made available open source at http://bfgl.anri.barc.usda.gov/ML/snp-phage/. Conclusion SNP-PHAGE provides a bioinformatics

  9. Alignment of time-resolved data from high throughput experiments.

    Science.gov (United States)

    Abidi, Nada; Franke, Raimo; Findeisen, Peter; Klawonn, Frank

    2016-12-01

    To better understand the dynamics of the underlying processes in cells, it is necessary to take measurements over a time course. Modern high-throughput technologies are often used for this purpose to measure the behavior of cell products like metabolites, peptides, proteins, [Formula: see text]RNA or mRNA at different points in time. Compared to classical time series, the number of time points is usually very limited and the measurements are taken at irregular time intervals. The main reasons for this are the costs of the experiments and the fact that the dynamic behavior usually shows a strong reaction and fast changes shortly after a stimulus and then slowly converges to a certain stable state. Another reason might simply be missing values. It is common to repeat the experiments and to have replicates in order to carry out a more reliable analysis. The ideal assumptions that the initial stimulus really started exactly at the same time for all replicates and that the replicates are perfectly synchronized are seldom satisfied. Therefore, there is a need to first adjust or align the time-resolved data before further analysis is carried out. Dynamic time warping (DTW) is considered as one of the common alignment techniques for time series data with equidistant time points. In this paper, we modified the DTW algorithm so that it can align sequences with measurements at different, non-equidistant time points with large gaps in between. This type of data is usually known as time-resolved data characterized by irregular time intervals between measurements as well as non-identical time points for different replicates. This new algorithm can be easily used to align time-resolved data from high-throughput experiments and to come across existing problems such as time scarcity and existing noise in the measurements. We propose a modified method of DTW to adapt requirements imposed by time-resolved data by use of monotone cubic interpolation splines. Our presented approach

  10. Laboratory study of nitrate photolysis in Antarctic snow. I. Observed quantum yield, domain of photolysis, and secondary chemistry

    DEFF Research Database (Denmark)

    Meusinger, Carl; Berhanu, Tesfaye A.; Erbland, Joseph

    2014-01-01

    undergoing secondary (recombination) chemistry. Modeled NOx emissions may increase significantly above measured values due to the observed quantum yield in this study. The apparent quantum yield in the 200 nm band was found to be ∼ 1%, much lower than reported for aqueous chemistry. A companion paper...... are understood. It has been shown that photolysis of nitrate in the snowpack plays a major role in nitrate loss and that the photolysis products have a significant influence on the local troposphere as well as on other species in the snow. Reported quantum yields for the main reaction spans orders of magnitude...

  11. Adaptation to high throughput batch chromatography enhances multivariate screening.

    Science.gov (United States)

    Barker, Gregory A; Calzada, Joseph; Herzer, Sibylle; Rieble, Siegfried

    2015-09-01

    High throughput process development offers unique approaches to explore complex process design spaces with relatively low material consumption. Batch chromatography is one technique that can be used to screen chromatographic conditions in a 96-well plate. Typical batch chromatography workflows examine variations in buffer conditions or comparison of multiple resins in a given process, as opposed to the assessment of protein loading conditions in combination with other factors. A modification to the batch chromatography paradigm is described here where experimental planning, programming, and a staggered loading approach increase the multivariate space that can be explored with a liquid handling system. The iterative batch chromatography (IBC) approach is described, which treats every well in a 96-well plate as an individual experiment, wherein protein loading conditions can be varied alongside other factors such as wash and elution buffer conditions. As all of these factors are explored in the same experiment, the interactions between them are characterized and the number of follow-up confirmatory experiments is reduced. This in turn improves statistical power and throughput. Two examples of the IBC method are shown and the impact of the load conditions are assessed in combination with the other factors explored. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. High Throughput Multispectral Image Processing with Applications in Food Science.

    Directory of Open Access Journals (Sweden)

    Panagiotis Tsakanikas

    Full Text Available Recently, machine vision is gaining attention in food science as well as in food industry concerning food quality assessment and monitoring. Into the framework of implementation of Process Analytical Technology (PAT in the food industry, image processing can be used not only in estimation and even prediction of food quality but also in detection of adulteration. Towards these applications on food science, we present here a novel methodology for automated image analysis of several kinds of food products e.g. meat, vanilla crème and table olives, so as to increase objectivity, data reproducibility, low cost information extraction and faster quality assessment, without human intervention. Image processing's outcome will be propagated to the downstream analysis. The developed multispectral image processing method is based on unsupervised machine learning approach (Gaussian Mixture Models and a novel unsupervised scheme of spectral band selection for segmentation process optimization. Through the evaluation we prove its efficiency and robustness against the currently available semi-manual software, showing that the developed method is a high throughput approach appropriate for massive data extraction from food samples.

  13. Assessing the utility and limitations of high throughput virtual screening

    Directory of Open Access Journals (Sweden)

    Paul Daniel Phillips

    2016-05-01

    Full Text Available Due to low cost, speed, and unmatched ability to explore large numbers of compounds, high throughput virtual screening and molecular docking engines have become widely utilized by computational scientists. It is generally accepted that docking engines, such as AutoDock, produce reliable qualitative results for ligand-macromolecular receptor binding, and molecular docking results are commonly reported in literature in the absence of complementary wet lab experimental data. In this investigation, three variants of the sixteen amino acid peptide, α-conotoxin MII, were docked to a homology model of the a3β2-nicotinic acetylcholine receptor. DockoMatic version 2.0 was used to perform a virtual screen of each peptide ligand to the receptor for ten docking trials consisting of 100 AutoDock cycles per trial. The results were analyzed for both variation in the calculated binding energy obtained from AutoDock, and the orientation of bound peptide within the receptor. The results show that, while no clear correlation exists between consistent ligand binding pose and the calculated binding energy, AutoDock is able to determine a consistent positioning of bound peptide in the majority of trials when at least ten trials were evaluated.

  14. BOOGIE: Predicting Blood Groups from High Throughput Sequencing Data.

    Science.gov (United States)

    Giollo, Manuel; Minervini, Giovanni; Scalzotto, Marta; Leonardi, Emanuela; Ferrari, Carlo; Tosatto, Silvio C E

    2015-01-01

    Over the last decade, we have witnessed an incredible growth in the amount of available genotype data due to high throughput sequencing (HTS) techniques. This information may be used to predict phenotypes of medical relevance, and pave the way towards personalized medicine. Blood phenotypes (e.g. ABO and Rh) are a purely genetic trait that has been extensively studied for decades, with currently over thirty known blood groups. Given the public availability of blood group data, it is of interest to predict these phenotypes from HTS data which may translate into more accurate blood typing in clinical practice. Here we propose BOOGIE, a fast predictor for the inference of blood groups from single nucleotide variant (SNV) databases. We focus on the prediction of thirty blood groups ranging from the well known ABO and Rh, to the less studied Junior or Diego. BOOGIE correctly predicted the blood group with 94% accuracy for the Personal Genome Project whole genome profiles where good quality SNV annotation was available. Additionally, our tool produces a high quality haplotype phase, which is of interest in the context of ethnicity-specific polymorphisms or traits. The versatility and simplicity of the analysis make it easily interpretable and allow easy extension of the protocol towards other phenotypes. BOOGIE can be downloaded from URL http://protein.bio.unipd.it/download/.

  15. Multiplexing a high-throughput liability assay to leverage efficiencies.

    Science.gov (United States)

    Herbst, John; Anthony, Monique; Stewart, Jeremy; Connors, David; Chen, Taosheng; Banks, Martyn; Petrillo, Edward W; Agler, Michele

    2009-06-01

    In order to identify potential cytochrome P-450 3A4 (drug-metabolizing enzyme) inducers at an early stage of the drug discovery process, a cell-based transactivation high-throughput luciferase reporter assay for the human pregnane X receptor (PXR) in HepG2 cells has been implemented and multiplexed with a viability end point for data interpretation, as part of a Lead Profiling portfolio of assays. As a routine part of Lead Profiling operations, assays are periodically evaluated for utility as well as for potential improvements in technology or process. We used a recent evaluation of our PXR-transactivation assay as a model for the application of Lean Thinking-based process analysis to lab-bench assay optimization and automation. This resulted in the development of a 384-well multiplexed homogeneous assay simultaneously detecting PXR transactivation and HepG2 cell cytotoxicity. In order to multiplex fluorescent and luminescent read-outs, modifications to each assay were necessary, which included optimization of multiple assay parameters such as cell density, plate type, and reagent concentrations. Subsequently, a set of compounds including known cytotoxic compounds and PXR inducers were used to validate the multiplexed assay. Results from the multiplexed assay correlate well with those from the singleplexed assay formats measuring PXR transactivation and viability separately. Implementation of the multiplexed assay for routine compound profiling provides improved data quality, sample conservation, cost savings, and resource efficiencies.

  16. High throughput reaction screening using desorption electrospray ionization mass spectrometry.

    Science.gov (United States)

    Wleklinski, Michael; Loren, Bradley P; Ferreira, Christina R; Jaman, Zinia; Avramova, Larisa; Sobreira, Tiago J P; Thompson, David H; Cooks, R Graham

    2018-02-14

    We report the high throughput analysis of reaction mixture arrays using methods and data handling routines that were originally developed for biological tissue imaging. Desorption electrospray ionization (DESI) mass spectrometry (MS) is applied in a continuous on-line process at rates that approach 10 4 reactions per h at area densities of up to 1 spot per mm 2 (6144 spots per standard microtiter plate) with the sprayer moving at ca. 10 4 microns per s. Data are analyzed automatically by MS using in-house software to create ion images of selected reagents and products as intensity plots in standard array format. Amine alkylation reactions were used to optimize the system performance on PTFE membrane substrates using methanol as the DESI spray/analysis solvent. Reaction times can be screening of processes like N -alkylation and Suzuki coupling reactions as reported herein. Products and by-products were confirmed by on-line MS/MS upon rescanning of the array.

  17. Tiered High-Throughput Screening Approach to Identify ...

    Science.gov (United States)

    High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the US EPA ToxCast screening assay portfolio. To fill one critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast Phase I and II chemical libraries, comprised of 1,074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single concentration screen were retested in concentration-response. Due to high false positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed two additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using

  18. High-Throughput Screening Using Mass Spectrometry within Drug Discovery.

    Science.gov (United States)

    Rohman, Mattias; Wingfield, Jonathan

    2016-01-01

    In order to detect a biochemical analyte with a mass spectrometer (MS) it is necessary to ionize the analyte of interest. The analyte can be ionized by a number of different mechanisms, however, one common method is electrospray ionization (ESI). Droplets of analyte are sprayed through a highly charged field, the droplets pick up charge, and this is transferred to the analyte. High levels of salt in the assay buffer will potentially steal charge from the analyte and suppress the MS signal. In order to avoid this suppression of signal, salt is often removed from the sample prior to injection into the MS. Traditional ESI MS relies on liquid chromatography (LC) to remove the salt and reduce matrix effects, however, this is a lengthy process. Here we describe the use of RapidFire™ coupled to a triple-quadrupole MS for high-throughput screening. This system uses solid-phase extraction to de-salt samples prior to injection, reducing processing time such that a sample is injected into the MS ~every 10 s.

  19. High-throughput screening of chemical effects on ...

    Science.gov (United States)

    Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2,060 chemical samples on steroidogenesis via HPLC-MS/MS quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a three stage screening strategy. The first stage established the maximum tolerated concentration (MTC; >70% viability) per sample. The second stage quantified changes in hormone levels at the MTC while the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were pre-stimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2,060 chemical samples evaluated, 524 samples were selected for six-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into five distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A d

  20. High Throughput Heuristics for Prioritizing Human Exposure to ...

    Science.gov (United States)

    The risk posed to human health by any of the thousands of untested anthropogenic chemicals in our environment is a function of both the potential hazard presented by the chemical, and the possibility of being exposed. Without the capacity to make quantitative, albeit uncertain, forecasts of exposure, the putative risk of adverse health effect from a chemical cannot be evaluated. We used Bayesian methodology to infer ranges of exposure intakes that are consistent with biomarkers of chemical exposures identified in urine samples from the U.S. population by the National Health and Nutrition Examination Survey (NHANES). We perform linear regression on inferred exposure for demographic subsets of NHANES demarked by age, gender, and weight using high throughput chemical descriptors gleaned from databases and chemical structure-based calculators. We find that five of these descriptors are capable of explaining roughly 50% of the variability across chemicals for all the demographic groups examined, including children aged 6-11. For the thousands of chemicals with no other source of information, this approach allows rapid and efficient prediction of average exposure intake of environmental chemicals. The methods described by this manuscript provide a highly improved methodology for HTS of human exposure to environmental chemicals. The manuscript includes a ranking of 7785 environmental chemicals with respect to potential human exposure, including most of the Tox21 in vit

  1. High-Throughput Identification of Antimicrobial Peptides from Amphibious Mudskippers

    Directory of Open Access Journals (Sweden)

    Yunhai Yi

    2017-11-01

    Full Text Available Widespread existence of antimicrobial peptides (AMPs has been reported in various animals with comprehensive biological activities, which is consistent with the important roles of AMPs as the first line of host defense system. However, no big-data-based analysis on AMPs from any fish species is available. In this study, we identified 507 AMP transcripts on the basis of our previously reported genomes and transcriptomes of two representative amphibious mudskippers, Boleophthalmus pectinirostris (BP and Periophthalmus magnuspinnatus (PM. The former is predominantly aquatic with less time out of water, while the latter is primarily terrestrial with extended periods of time on land. Within these identified AMPs, 449 sequences are novel; 15 were reported in BP previously; 48 are identically overlapped between BP and PM; 94 were validated by mass spectrometry. Moreover, most AMPs presented differential tissue transcription patterns in the two mudskippers. Interestingly, we discovered two AMPs, hemoglobin β1 and amylin, with high inhibitions on Micrococcus luteus. In conclusion, our high-throughput screening strategy based on genomic and transcriptomic data opens an efficient pathway to discover new antimicrobial peptides for ongoing development of marine drugs.

  2. High-Throughput Identification of Antimicrobial Peptides from Amphibious Mudskippers.

    Science.gov (United States)

    Yi, Yunhai; You, Xinxin; Bian, Chao; Chen, Shixi; Lv, Zhao; Qiu, Limei; Shi, Qiong

    2017-11-22

    Widespread existence of antimicrobial peptides (AMPs) has been reported in various animals with comprehensive biological activities, which is consistent with the important roles of AMPs as the first line of host defense system. However, no big-data-based analysis on AMPs from any fish species is available. In this study, we identified 507 AMP transcripts on the basis of our previously reported genomes and transcriptomes of two representative amphibious mudskippers, Boleophthalmus pectinirostris (BP) and Periophthalmus magnuspinnatus (PM). The former is predominantly aquatic with less time out of water, while the latter is primarily terrestrial with extended periods of time on land. Within these identified AMPs, 449 sequences are novel; 15 were reported in BP previously; 48 are identically overlapped between BP and PM; 94 were validated by mass spectrometry. Moreover, most AMPs presented differential tissue transcription patterns in the two mudskippers. Interestingly, we discovered two AMPs, hemoglobin β1 and amylin, with high inhibitions on Micrococcus luteus . In conclusion, our high-throughput screening strategy based on genomic and transcriptomic data opens an efficient pathway to discover new antimicrobial peptides for ongoing development of marine drugs.

  3. [Morphometry of pulmonary tissue: From manual to high throughput automation].

    Science.gov (United States)

    Sallon, C; Soulet, D; Tremblay, Y

    2017-12-01

    Weibel's research has shown that any alteration of the pulmonary structure has effects on function. This demonstration required a quantitative analysis of lung structures called morphometry. This is possible thanks to stereology, a set of methods based on principles of geometry and statistics. His work has helped to better understand the morphological harmony of the lung, which is essential for its proper functioning. An imbalance leads to pathophysiology such as chronic obstructive pulmonary disease in adults and bronchopulmonary dysplasia in neonates. It is by studying this imbalance that new therapeutic approaches can be developed. These advances are achievable only through morphometric analytical methods, which are increasingly precise and focused, in particular thanks to the high-throughput automation of these methods. This review makes a comparison between an automated method that we developed in the laboratory and semi-manual methods of morphometric analyzes. The automation of morphometric measurements is a fundamental asset in the study of pulmonary pathophysiology because it is an assurance of robustness, reproducibility and speed. This tool will thus contribute significantly to the acceleration of the race for the development of new drugs. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  4. Use of High Throughput Screening Data in IARC Monograph ...

    Science.gov (United States)

    Purpose: Evaluation of carcinogenic mechanisms serves a critical role in IARC monograph evaluations, and can lead to “upgrade” or “downgrade” of the carcinogenicity conclusions based on human and animal evidence alone. Three recent IARC monograph Working Groups (110, 112, and 113) pioneered analysis of high throughput in vitro screening data from the U.S. Environmental Protection Agency’s ToxCast program in evaluations of carcinogenic mechanisms. Methods: For monograph 110, ToxCast assay data across multiple nuclear receptors were used to test the hypothesis that PFOA acts exclusively through the PPAR family of receptors, with activity profiles compared to several prototypical nuclear receptor-activating compounds. For monographs 112 and 113, ToxCast assays were systematically evaluated and used as an additional data stream in the overall evaluation of the mechanistic evidence. Specifically, ToxCast assays were mapped to 10 “key characteristics of carcinogens” recently identified by an IARC expert group, and chemicals’ bioactivity profiles were evaluated both in absolute terms (number of relevant assays positive for bioactivity) and relative terms (ranking with respect to other compounds evaluated by IARC, using the ToxPi methodology). Results: PFOA activates multiple nuclear receptors in addition to the PPAR family in the ToxCast assays. ToxCast assays offered substantial coverage for 5 of the 10 “key characteristics,” with the greates

  5. Management of High-Throughput DNA Sequencing Projects: Alpheus.

    Science.gov (United States)

    Miller, Neil A; Kingsmore, Stephen F; Farmer, Andrew; Langley, Raymond J; Mudge, Joann; Crow, John A; Gonzalez, Alvaro J; Schilkey, Faye D; Kim, Ryan J; van Velkinburgh, Jennifer; May, Gregory D; Black, C Forrest; Myers, M Kathy; Utsey, John P; Frost, Nicholas S; Sugarbaker, David J; Bueno, Raphael; Gullans, Stephen R; Baxter, Susan M; Day, Steve W; Retzel, Ernest F

    2008-12-26

    High-throughput DNA sequencing has enabled systems biology to begin to address areas in health, agricultural and basic biological research. Concomitant with the opportunities is an absolute necessity to manage significant volumes of high-dimensional and inter-related data and analysis. Alpheus is an analysis pipeline, database and visualization software for use with massively parallel DNA sequencing technologies that feature multi-gigabase throughput characterized by relatively short reads, such as Illumina-Solexa (sequencing-by-synthesis), Roche-454 (pyrosequencing) and Applied Biosystem's SOLiD (sequencing-by-ligation). Alpheus enables alignment to reference sequence(s), detection of variants and enumeration of sequence abundance, including expression levels in transcriptome sequence. Alpheus is able to detect several types of variants, including non-synonymous and synonymous single nucleotide polymorphisms (SNPs), insertions/deletions (indels), premature stop codons, and splice isoforms. Variant detection is aided by the ability to filter variant calls based on consistency, expected allele frequency, sequence quality, coverage, and variant type in order to minimize false positives while maximizing the identification of true positives. Alpheus also enables comparisons of genes with variants between cases and controls or bulk segregant pools. Sequence-based differential expression comparisons can be developed, with data export to SAS JMP Genomics for statistical analysis.

  6. High-Throughput Network Communication with NetIO

    CERN Document Server

    Schumacher, J\\"orn; The ATLAS collaboration; Vandelli, Wainer

    2016-01-01

    HPC network technologies like Infiniband, TrueScale or OmniPath provide low-latency and high-throughput communication between hosts, which makes them attractive options for data-acquisition systems in large-scale high-energy physics experiments. Like HPC networks, DAQ networks are local and include a well specified number of systems. Unfortunately traditional network communication APIs for HPC clusters like MPI or PGAS target exclusively the HPC community and are not suited well for DAQ applications. It is possible to build distributed DAQ applications using low-level system APIs like Infiniband Verbs (and this has been done), but it requires a non negligible effort and expert knowledge. On the other hand, message services like 0MQ have gained popularity in the HEP community. Such APIs allow to build distributed applications with a high-level approach and provide good performance. Unfortunately their usage usually limits developers to TCP/IP-based networks. While it is possible to operate a TCP/IP stack on to...

  7. High Throughput Sequencing for Detection of Foodborne Pathogens

    Directory of Open Access Journals (Sweden)

    Camilla Sekse

    2017-10-01

    Full Text Available High-throughput sequencing (HTS is becoming the state-of-the-art technology for typing of microbial isolates, especially in clinical samples. Yet, its application is still in its infancy for monitoring and outbreak investigations of foods. Here we review the published literature, covering not only bacterial but also viral and Eukaryote food pathogens, to assess the status and potential of HTS implementation to inform stakeholders, improve food safety and reduce outbreak impacts. The developments in sequencing technology and bioinformatics have outpaced the capacity to analyze and interpret the sequence data. The influence of sample processing, nucleic acid extraction and purification, harmonized protocols for generation and interpretation of data, and properly annotated and curated reference databases including non-pathogenic “natural” strains are other major obstacles to the realization of the full potential of HTS in analytical food surveillance, epidemiological and outbreak investigations, and in complementing preventive approaches for the control and management of foodborne pathogens. Despite significant obstacles, the achieved progress in capacity and broadening of the application range over the last decade is impressive and unprecedented, as illustrated with the chosen examples from the literature. Large consortia, often with broad international participation, are making coordinated efforts to cope with many of the mentioned obstacles. Further rapid progress can therefore be prospected for the next decade.

  8. Using high-throughput barcode sequencing to efficiently map connectomes.

    Science.gov (United States)

    Peikon, Ian D; Kebschull, Justus M; Vagin, Vasily V; Ravens, Diana I; Sun, Yu-Chi; Brouzes, Eric; Corrêa, Ivan R; Bressan, Dario; Zador, Anthony M

    2017-07-07

    The function of a neural circuit is determined by the details of its synaptic connections. At present, the only available method for determining a neural wiring diagram with single synapse precision-a 'connectome'-is based on imaging methods that are slow, labor-intensive and expensive. Here, we present SYNseq, a method for converting the connectome into a form that can exploit the speed and low cost of modern high-throughput DNA sequencing. In SYNseq, each neuron is labeled with a unique random nucleotide sequence-an RNA 'barcode'-which is targeted to the synapse using engineered proteins. Barcodes in pre- and postsynaptic neurons are then associated through protein-protein crosslinking across the synapse, extracted from the tissue, and joined into a form suitable for sequencing. Although our failure to develop an efficient barcode joining scheme precludes the widespread application of this approach, we expect that with further development SYNseq will enable tracing of complex circuits at high speed and low cost. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Dimensioning storage and computing clusters for efficient high throughput computing

    International Nuclear Information System (INIS)

    Accion, E; Bria, A; Bernabeu, G; Caubet, M; Delfino, M; Espinal, X; Merino, G; Lopez, F; Martinez, F; Planas, E

    2012-01-01

    Scientific experiments are producing huge amounts of data, and the size of their datasets and total volume of data continues increasing. These data are then processed by researchers belonging to large scientific collaborations, with the Large Hadron Collider being a good example. The focal point of scientific data centers has shifted from efficiently coping with PetaByte scale storage to deliver quality data processing throughput. The dimensioning of the internal components in High Throughput Computing (HTC) data centers is of crucial importance to cope with all the activities demanded by the experiments, both the online (data acceptance) and the offline (data processing, simulation and user analysis). This requires a precise setup involving disk and tape storage services, a computing cluster and the internal networking to prevent bottlenecks, overloads and undesired slowness that lead to losses cpu cycles and batch jobs failures. In this paper we point out relevant features for running a successful data storage and processing service in an intensive HTC environment.

  10. High Throughput Multispectral Image Processing with Applications in Food Science.

    Science.gov (United States)

    Tsakanikas, Panagiotis; Pavlidis, Dimitris; Nychas, George-John

    2015-01-01

    Recently, machine vision is gaining attention in food science as well as in food industry concerning food quality assessment and monitoring. Into the framework of implementation of Process Analytical Technology (PAT) in the food industry, image processing can be used not only in estimation and even prediction of food quality but also in detection of adulteration. Towards these applications on food science, we present here a novel methodology for automated image analysis of several kinds of food products e.g. meat, vanilla crème and table olives, so as to increase objectivity, data reproducibility, low cost information extraction and faster quality assessment, without human intervention. Image processing's outcome will be propagated to the downstream analysis. The developed multispectral image processing method is based on unsupervised machine learning approach (Gaussian Mixture Models) and a novel unsupervised scheme of spectral band selection for segmentation process optimization. Through the evaluation we prove its efficiency and robustness against the currently available semi-manual software, showing that the developed method is a high throughput approach appropriate for massive data extraction from food samples.

  11. Advances in High Throughput Screening of Biomass Recalcitrance (Poster)

    Energy Technology Data Exchange (ETDEWEB)

    Turner, G. B.; Decker, S. R.; Tucker, M. P.; Law, C.; Doeppke, C.; Sykes, R. W.; Davis, M. F.; Ziebell, A.

    2012-06-01

    This was a poster displayed at the Symposium. Advances on previous high throughput screening of biomass recalcitrance methods have resulted in improved conversion and replicate precision. Changes in plate reactor metallurgy, improved preparation of control biomass, species-specific pretreatment conditions, and enzymatic hydrolysis parameters have reduced overall coefficients of variation to an average of 6% for sample replicates. These method changes have improved plate-to-plate variation of control biomass recalcitrance and improved confidence in sugar release differences between samples. With smaller errors plant researchers can have a higher degree of assurance more low recalcitrance candidates can be identified. Significant changes in plate reactor, control biomass preparation, pretreatment conditions and enzyme have significantly reduced sample and control replicate variability. Reactor plate metallurgy significantly impacts sugar release aluminum leaching into reaction during pretreatment degrades sugars and inhibits enzyme activity. Removal of starch and extractives significantly decreases control biomass variability. New enzyme formulations give more consistent and higher conversion levels, however required re-optimization for switchgrass. Pretreatment time and temperature (severity) should be adjusted to specific biomass types i.e. woody vs. herbaceous. Desalting of enzyme preps to remove low molecular weight stabilizers and improved conversion levels likely due to water activity impacts on enzyme structure and substrate interactions not attempted here due to need to continually desalt and validate precise enzyme concentration and activity.

  12. High-Throughput Printing Process for Flexible Electronics

    Science.gov (United States)

    Hyun, Woo Jin

    Printed electronics is an emerging field for manufacturing electronic devices with low cost and minimal material waste for a variety of applications including displays, distributed sensing, smart packaging, and energy management. Moreover, its compatibility with roll-to-roll production formats and flexible substrates is desirable for continuous, high-throughput production of flexible electronics. Despite the promise, however, the roll-to-roll production of printed electronics is quite challenging due to web movement hindering accurate ink registration and high-fidelity printing. In this talk, I will present a promising strategy for roll-to-roll production using a novel printing process that we term SCALE (Self-aligned Capillarity-Assisted Lithography for Electronics). By utilizing capillarity of liquid inks on nano/micro-structured substrates, the SCALE process facilitates high-resolution and self-aligned patterning of electrically functional inks with greatly improved printing tolerance. I will show the fabrication of key building blocks (e.g. transistor, resistor, capacitor) for electronic circuits using the SCALE process on plastics.

  13. High-throughput selection for cellulase catalysts using chemical complementation.

    Science.gov (United States)

    Peralta-Yahya, Pamela; Carter, Brian T; Lin, Hening; Tao, Haiyan; Cornish, Virginia W

    2008-12-24

    Efficient enzymatic hydrolysis of lignocellulosic material remains one of the major bottlenecks to cost-effective conversion of biomass to ethanol. Improvement of glycosylhydrolases, however, is limited by existing medium-throughput screening technologies. Here, we report the first high-throughput selection for cellulase catalysts. This selection was developed by adapting chemical complementation to provide a growth assay for bond cleavage reactions. First, a URA3 counter selection was adapted to link chemical dimerizer activated gene transcription to cell death. Next, the URA3 counter selection was shown to detect cellulase activity based on cleavage of a tetrasaccharide chemical dimerizer substrate and decrease in expression of the toxic URA3 reporter. Finally, the utility of the cellulase selection was assessed by isolating cellulases with improved activity from a cellulase library created by family DNA shuffling. This application provides further evidence that chemical complementation can be readily adapted to detect different enzymatic activities for important chemical transformations for which no natural selection exists. Because of the large number of enzyme variants that selections can now test as compared to existing medium-throughput screens for cellulases, this assay has the potential to impact the discovery of improved cellulases and other glycosylhydrolases for biomass conversion from libraries of cellulases created by mutagenesis or obtained from natural biodiversity.

  14. Towards Prebiotic Catalytic Amyloids Using High Throughput Screening.

    Directory of Open Access Journals (Sweden)

    Michael P Friedmann

    Full Text Available Enzymes are capable of directing complex stereospecific transformations and of accelerating reaction rates many orders of magnitude. As even the simplest known enzymes comprise thousands of atoms, the question arises as to how such exquisite catalysts evolved. A logical predecessor would be shorter peptides, but they lack the defined structure and size that are apparently necessary for enzyme functions. However, some very short peptides are able to assemble into amyloids, thereby forming a well-defined tertiary structure called the cross-β-sheet, which bestows unique properties upon the peptides. We have hypothesized that amyloids could have been the catalytically active precursor to modern enzymes. To test this hypothesis, we designed an amyloid peptide library that could be screened for catalytic activity. Our approach, amenable to high-throughput methodologies, allowed us to find several peptides and peptide mixtures that form amyloids with esterase activity. These results indicate that amyloids, with their stability in a wide range of conditions and their potential as catalysts with low sequence specificity, would indeed be fitting precursors to modern enzymes. Furthermore, our approach can be efficiently expanded upon in library size, screening conditions, and target activity to yield novel amyloid catalysts with potential applications in aqueous-organic mixtures, at high temperature and in other extreme conditions that could be advantageous for industrial applications.

  15. Probabilistic Methods for Processing High-Throughput Sequencing Signals

    DEFF Research Database (Denmark)

    Sørensen, Lasse Maretty

    High-throughput sequencing has the potential to answer many of the big questions in biology and medicine. It can be used to determine the ancestry of species, to chart complex ecosystems and to understand and diagnose disease. However, going from raw sequencing data to biological or medical insig....... By estimating the genotypes on a set of candidate variants obtained from both a standard mapping-based approach as well as de novo assemblies, we are able to find considerably more structural variation than previous studies...... for reconstructing transcript sequences from RNA sequencing data. The method is based on a novel sparse prior distribution over transcript abundances and is markedly more accurate than existing approaches. The second chapter describes a new method for calling genotypes from a fixed set of candidate variants....... The method queries the reads using a graph representation of the variants and hereby mitigates the reference-bias that characterise standard genotyping methods. In the last chapter, we apply this method to call the genotypes of 50 deeply sequencing parent-offspring trios from the GenomeDenmark project...

  16. Efficient visualization of high-throughput targeted proteomics experiments: TAPIR.

    Science.gov (United States)

    Röst, Hannes L; Rosenberger, George; Aebersold, Ruedi; Malmström, Lars

    2015-07-15

    Targeted mass spectrometry comprises a set of powerful methods to obtain accurate and consistent protein quantification in complex samples. To fully exploit these techniques, a cross-platform and open-source software stack based on standardized data exchange formats is required. We present TAPIR, a fast and efficient Python visualization software for chromatograms and peaks identified in targeted proteomics experiments. The input formats are open, community-driven standardized data formats (mzML for raw data storage and TraML encoding the hierarchical relationships between transitions, peptides and proteins). TAPIR is scalable to proteome-wide targeted proteomics studies (as enabled by SWATH-MS), allowing researchers to visualize high-throughput datasets. The framework integrates well with existing automated analysis pipelines and can be extended beyond targeted proteomics to other types of analyses. TAPIR is available for all computing platforms under the 3-clause BSD license at https://github.com/msproteomicstools/msproteomicstools. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Quantifying Nanoparticle Internalization Using a High Throughput Internalization Assay.

    Science.gov (United States)

    Mann, Sarah K; Czuba, Ewa; Selby, Laura I; Such, Georgina K; Johnston, Angus P R

    2016-10-01

    The internalization of nanoparticles into cells is critical for effective nanoparticle mediated drug delivery. To investigate the kinetics and mechanism of internalization of nanoparticles into cells we have developed a DNA molecular sensor, termed the Specific Hybridization Internalization Probe - SHIP. Self-assembling polymeric 'pHlexi' nanoparticles were functionalized with a Fluorescent Internalization Probe (FIP) and the interactions with two different cell lines (3T3 and CEM cells) were studied. The kinetics of internalization were quantified and chemical inhibitors that inhibited energy dependent endocytosis (sodium azide), dynamin dependent endocytosis (Dyngo-4a) and macropinocytosis (5-(N-ethyl-N-isopropyl) amiloride (EIPA)) were used to study the mechanism of internalization. Nanoparticle internalization kinetics were significantly faster in 3T3 cells than CEM cells. We have shown that ~90% of the nanoparticles associated with 3T3 cells were internalized, compared to only 20% of the nanoparticles associated with CEM cells. Nanoparticle uptake was via a dynamin-dependent pathway, and the nanoparticles were trafficked to lysosomal compartments once internalized. SHIP is able to distinguish between nanoparticles that are associated on the outer cell membrane from nanoparticles that are internalized. This study demonstrates the assay can be used to probe the kinetics of nanoparticle internalization and the mechanisms by which the nanoparticles are taken up by cells. This information is fundamental for engineering more effective nanoparticle delivery systems. The SHIP assay is a simple and a high-throughput technique that could have wide application in therapeutic delivery research.

  18. High-Throughput Analysis and Automation for Glycomics Studies.

    Science.gov (United States)

    Shubhakar, Archana; Reiding, Karli R; Gardner, Richard A; Spencer, Daniel I R; Fernandes, Daryl L; Wuhrer, Manfred

    This review covers advances in analytical technologies for high-throughput (HTP) glycomics. Our focus is on structural studies of glycoprotein glycosylation to support biopharmaceutical realization and the discovery of glycan biomarkers for human disease. For biopharmaceuticals, there is increasing use of glycomics in Quality by Design studies to help optimize glycan profiles of drugs with a view to improving their clinical performance. Glycomics is also used in comparability studies to ensure consistency of glycosylation both throughout product development and between biosimilars and innovator drugs. In clinical studies there is as well an expanding interest in the use of glycomics-for example in Genome Wide Association Studies-to follow changes in glycosylation patterns of biological tissues and fluids with the progress of certain diseases. These include cancers, neurodegenerative disorders and inflammatory conditions. Despite rising activity in this field, there are significant challenges in performing large scale glycomics studies. The requirement is accurate identification and quantitation of individual glycan structures. However, glycoconjugate samples are often very complex and heterogeneous and contain many diverse branched glycan structures. In this article we cover HTP sample preparation and derivatization methods, sample purification, robotization, optimized glycan profiling by UHPLC, MS and multiplexed CE, as well as hyphenated techniques and automated data analysis tools. Throughout, we summarize the advantages and challenges with each of these technologies. The issues considered include reliability of the methods for glycan identification and quantitation, sample throughput, labor intensity, and affordability for large sample numbers.

  19. High Throughput T Epitope Mapping and Vaccine Development

    Directory of Open Access Journals (Sweden)

    Giuseppina Li Pira

    2010-01-01

    Full Text Available Mapping of antigenic peptide sequences from proteins of relevant pathogens recognized by T helper (Th and by cytolytic T lymphocytes (CTL is crucial for vaccine development. In fact, mapping of T-cell epitopes provides useful information for the design of peptide-based vaccines and of peptide libraries to monitor specific cellular immunity in protected individuals, patients and vaccinees. Nevertheless, epitope mapping is a challenging task. In fact, large panels of overlapping peptides need to be tested with lymphocytes to identify the sequences that induce a T-cell response. Since numerous peptide panels from antigenic proteins are to be screened, lymphocytes available from human subjects are a limiting factor. To overcome this limitation, high throughput (HTP approaches based on miniaturization and automation of T-cell assays are needed. Here we consider the most recent applications of the HTP approach to T epitope mapping. The alternative or complementary use of in silico prediction and experimental epitope definition is discussed in the context of the recent literature. The currently used methods are described with special reference to the possibility of applying the HTP concept to make epitope mapping an easier procedure in terms of time, workload, reagents, cells and overall cost.

  20. High-throughput literature mining to support read-across ...

    Science.gov (United States)

    Building scientific confidence in the development and evaluation of read-across remains an ongoing challenge. Approaches include establishing systematic frameworks to identify sources of uncertainty and ways to address them. One source of uncertainty is related to characterizing biological similarity. Many research efforts are underway such as structuring mechanistic data in adverse outcome pathways and investigating the utility of high throughput (HT)/high content (HC) screening data. A largely untapped resource for read-across to date is the biomedical literature. This information has the potential to support read-across by facilitating the identification of valid source analogues with similar biological and toxicological profiles as well as providing the mechanistic understanding for any prediction made. A key challenge in using biomedical literature is to convert and translate its unstructured form into a computable format that can be linked to chemical structure. We developed a novel text-mining strategy to represent literature information for read across. Keywords were used to organize literature into toxicity signatures at the chemical level. These signatures were integrated with HT in vitro data and curated chemical structures. A rule-based algorithm assessed the strength of the literature relationship, providing a mechanism to rank and visualize the signature as literature ToxPIs (LitToxPIs). LitToxPIs were developed for over 6,000 chemicals for a varie

  1. High-Throughput DNA sequencing of ancient wood.

    Science.gov (United States)

    Wagner, Stefanie; Lagane, Frédéric; Seguin-Orlando, Andaine; Schubert, Mikkel; Leroy, Thibault; Guichoux, Erwan; Chancerel, Emilie; Bech-Hebelstrup, Inger; Bernard, Vincent; Billard, Cyrille; Billaud, Yves; Bolliger, Matthias; Croutsch, Christophe; Čufar, Katarina; Eynaud, Frédérique; Heussner, Karl Uwe; Köninger, Joachim; Langenegger, Fabien; Leroy, Frédéric; Lima, Christine; Martinelli, Nicoletta; Momber, Garry; Billamboz, André; Nelle, Oliver; Palomo, Antoni; Piqué, Raquel; Ramstein, Marianne; Schweichel, Roswitha; Stäuble, Harald; Tegel, Willy; Terradas, Xavier; Verdin, Florence; Plomion, Christophe; Kremer, Antoine; Orlando, Ludovic

    2018-03-01

    Reconstructing the colonization and demographic dynamics that gave rise to extant forests is essential to forecasts of forest responses to environmental changes. Classical approaches to map how population of trees changed through space and time largely rely on pollen distribution patterns, with only a limited number of studies exploiting DNA molecules preserved in wooden tree archaeological and subfossil remains. Here, we advance such analyses by applying high-throughput (HTS) DNA sequencing to wood archaeological and subfossil material for the first time, using a comprehensive sample of 167 European white oak waterlogged remains spanning a large temporal (from 550 to 9,800 years) and geographical range across Europe. The successful characterization of the endogenous DNA and exogenous microbial DNA of 140 (~83%) samples helped the identification of environmental conditions favouring long-term DNA preservation in wood remains, and started to unveil the first trends in the DNA decay process in wood material. Additionally, the maternally inherited chloroplast haplotypes of 21 samples from three periods of forest human-induced use (Neolithic, Bronze Age and Middle Ages) were found to be consistent with those of modern populations growing in the same geographic areas. Our work paves the way for further studies aiming at using ancient DNA preserved in wood to reconstruct the micro-evolutionary response of trees to climate change and human forest management. © 2018 John Wiley & Sons Ltd.

  2. Quantum Chemistry beyond Born–Oppenheimer Approximation on a Quantum Computer: A Simulated Phase Estimation Study

    Czech Academy of Sciences Publication Activity Database

    Veis, Libor; Višňák, Jakub; Nishizawa, H.; Nakai, H.; Pittner, Jiří

    2016-01-01

    Roč. 116, č. 18 (2016), s. 1328-1336 ISSN 0020-7608 R&D Projects: GA ČR GA203/08/0626 Institutional support: RVO:61388955 Keywords : Born-Oppenheimer approximation * nuclear orbital plus molecular orbital method * phase estimation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.920, year: 2016

  3. Standardized Method for High-throughput Sterilization of Arabidopsis Seeds.

    Science.gov (United States)

    Lindsey, Benson E; Rivero, Luz; Calhoun, Chistopher S; Grotewold, Erich; Brkljacic, Jelena

    2017-10-17

    Arabidopsis thaliana (Arabidopsis) seedlings often need to be grown on sterile media. This requires prior seed sterilization to prevent the growth of microbial contaminants present on the seed surface. Currently, Arabidopsis seeds are sterilized using two distinct sterilization techniques in conditions that differ slightly between labs and have not been standardized, often resulting in only partially effective sterilization or in excessive seed mortality. Most of these methods are also not easily scalable to a large number of seed lines of diverse genotypes. As technologies for high-throughput analysis of Arabidopsis continue to proliferate, standardized techniques for sterilizing large numbers of seeds of different genotypes are becoming essential for conducting these types of experiments. The response of a number of Arabidopsis lines to two different sterilization techniques was evaluated based on seed germination rate and the level of seed contamination with microbes and other pathogens. The treatments included different concentrations of sterilizing agents and times of exposure, combined to determine optimal conditions for Arabidopsis seed sterilization. Optimized protocols have been developed for two different sterilization methods: bleach (liquid-phase) and chlorine (Cl2) gas (vapor-phase), both resulting in high seed germination rates and minimal microbial contamination. The utility of these protocols was illustrated through the testing of both wild type and mutant seeds with a range of germination potentials. Our results show that seeds can be effectively sterilized using either method without excessive seed mortality, although detrimental effects of sterilization were observed for seeds with lower than optimal germination potential. In addition, an equation was developed to enable researchers to apply the standardized chlorine gas sterilization conditions to airtight containers of different sizes. The protocols described here allow easy, efficient, and

  4. Mining Chemical Activity Status from High-Throughput Screening Assays

    KAUST Repository

    Soufan, Othman

    2015-12-14

    High-throughput screening (HTS) experiments provide a valuable resource that reports biological activity of numerous chemical compounds relative to their molecular targets. Building computational models that accurately predict such activity status (active vs. inactive) in specific assays is a challenging task given the large volume of data and frequently small proportion of active compounds relative to the inactive ones. We developed a method, DRAMOTE, to predict activity status of chemical compounds in HTP activity assays. For a class of HTP assays, our method achieves considerably better results than the current state-of-the-art-solutions. We achieved this by modification of a minority oversampling technique. To demonstrate that DRAMOTE is performing better than the other methods, we performed a comprehensive comparison analysis with several other methods and evaluated them on data from 11 PubChem assays through 1,350 experiments that involved approximately 500,000 interactions between chemicals and their target proteins. As an example of potential use, we applied DRAMOTE to develop robust models for predicting FDA approved drugs that have high probability to interact with the thyroid stimulating hormone receptor (TSHR) in humans. Our findings are further partially and indirectly supported by 3D docking results and literature information. The results based on approximately 500,000 interactions suggest that DRAMOTE has performed the best and that it can be used for developing robust virtual screening models. The datasets and implementation of all solutions are available as a MATLAB toolbox online at www.cbrc.kaust.edu.sa/dramote and can be found on Figshare.

  5. Using In Vitro High-Throughput Screening Data for Predicting ...

    Science.gov (United States)

    Today there are more than 80,000 chemicals in commerce and the environment. The potential human health risks are unknown for the vast majority of these chemicals as they lack human health risk assessments, toxicity reference values and risk screening values. We aim to use computational toxicology and quantitative high throughput screening (qHTS) technologies to fill these data gaps, and begin to prioritize these chemicals for additional assessment. By coupling qHTS data with adverse outcome pathways (AOPs) we can use ontologies to make predictions about potential hazards and to identify those assays which are sufficient to infer these same hazards. Once those assays are identified, we can use bootstrap natural spline-based metaregression to integrate the evidence across multiple replicates or assays (if a combination of assays are together necessary to be sufficient). In this pilot, we demonstrate how we were able to identify that benzo[k]fluoranthene (B[k]F) may induce DNA damage and steatosis using qHTS data and two separate AOPs. We also demonstrate how bootstrap natural spline-based metaregression can be used to integrate the data across multiple assay replicates to generate a concentration-response curve. We used this analysis to calculate an internal point of departure of 0.751µM and risk-specific concentrations of 0.378µM for both 1:1,000 and 1:10,000 additive risk for B[k]F induced DNA damage based on the p53 assay. Based on the available evidence, we

  6. Towards high throughput screening of electrochemical stability of battery electrolytes

    International Nuclear Information System (INIS)

    Borodin, Oleg; Olguin, Marco; Spear, Carrie E; Leiter, Kenneth W; Knap, Jaroslaw

    2015-01-01

    High throughput screening of solvents and additives with potential applications in lithium batteries is reported. The initial test set is limited to carbonate and phosphate-based compounds and focused on their electrochemical properties. Solvent stability towards first and second reduction and oxidation is reported from density functional theory (DFT) calculations performed on isolated solvents surrounded by implicit solvent. The reorganization energy is estimated from the difference between vertical and adiabatic redox energies and found to be especially important for the accurate prediction of reduction stability. A majority of tested compounds had the second reduction potential higher than the first reduction potential indicating that the second reduction reaction might play an important role in the passivation layer formation. Similarly, the second oxidation potential was smaller for a significant subset of tested molecules than the first oxidation potential. A number of potential sources of errors introduced during screening of the electrolyte electrochemical properties were examined. The formation of lithium fluoride during reduction of semifluorinated solvents such as fluoroethylene carbonate and the H-transfer during oxidation of solvents were found to shift the electrochemical potential by 1.5–2 V and could shrink the electrochemical stability window by as much as 3.5 V when such reactions are included in the screening procedure. The initial oxidation reaction of ethylene carbonate and dimethyl carbonate at the surface of the completely de-lithiated LiNi 0.5 Mn 1.5 O 4 high voltage spinel cathode was examined using DFT. Depending on the molecular orientation at the cathode surface, a carbonate molecule either exhibited deprotonation or was found bound to the transition metal via its carbonyl oxygen. (paper)

  7. Mining Chemical Activity Status from High-Throughput Screening Assays

    KAUST Repository

    Soufan, Othman; Ba Alawi, Wail; Afeef, Moataz A.; Essack, Magbubah; Rodionov, Valentin; Kalnis, Panos; Bajic, Vladimir B.

    2015-01-01

    High-throughput screening (HTS) experiments provide a valuable resource that reports biological activity of numerous chemical compounds relative to their molecular targets. Building computational models that accurately predict such activity status (active vs. inactive) in specific assays is a challenging task given the large volume of data and frequently small proportion of active compounds relative to the inactive ones. We developed a method, DRAMOTE, to predict activity status of chemical compounds in HTP activity assays. For a class of HTP assays, our method achieves considerably better results than the current state-of-the-art-solutions. We achieved this by modification of a minority oversampling technique. To demonstrate that DRAMOTE is performing better than the other methods, we performed a comprehensive comparison analysis with several other methods and evaluated them on data from 11 PubChem assays through 1,350 experiments that involved approximately 500,000 interactions between chemicals and their target proteins. As an example of potential use, we applied DRAMOTE to develop robust models for predicting FDA approved drugs that have high probability to interact with the thyroid stimulating hormone receptor (TSHR) in humans. Our findings are further partially and indirectly supported by 3D docking results and literature information. The results based on approximately 500,000 interactions suggest that DRAMOTE has performed the best and that it can be used for developing robust virtual screening models. The datasets and implementation of all solutions are available as a MATLAB toolbox online at www.cbrc.kaust.edu.sa/dramote and can be found on Figshare.

  8. Towards Chip Scale Liquid Chromatography and High Throughput Immunosensing

    Energy Technology Data Exchange (ETDEWEB)

    Ni, Jing [Iowa State Univ., Ames, IA (United States)

    2000-09-21

    This work describes several research projects aimed towards developing new instruments and novel methods for high throughput chemical and biological analysis. Approaches are taken in two directions. The first direction takes advantage of well-established semiconductor fabrication techniques and applies them to miniaturize instruments that are workhorses in analytical laboratories. Specifically, the first part of this work focused on the development of micropumps and microvalves for controlled fluid delivery. The mechanism of these micropumps and microvalves relies on the electrochemically-induced surface tension change at a mercury/electrolyte interface. A miniaturized flow injection analysis device was integrated and flow injection analyses were demonstrated. In the second part of this work, microfluidic chips were also designed, fabricated, and tested. Separations of two fluorescent dyes were demonstrated in microfabricated channels, based on an open-tubular liquid chromatography (OT LC) or an electrochemically-modulated liquid chromatography (EMLC) format. A reduction in instrument size can potentially increase analysis speed, and allow exceedingly small amounts of sample to be analyzed under diverse separation conditions. The second direction explores the surface enhanced Raman spectroscopy (SERS) as a signal transduction method for immunoassay analysis. It takes advantage of the improved detection sensitivity as a result of surface enhancement on colloidal gold, the narrow width of Raman band, and the stability of Raman scattering signals to distinguish several different species simultaneously without exploiting spatially-separated addresses on a biochip. By labeling gold nanoparticles with different Raman reporters in conjunction with different detection antibodies, a simultaneous detection of a dual-analyte immunoassay was demonstrated. Using this scheme for quantitative analysis was also studied and preliminary dose-response curves from an immunoassay of a

  9. A bioimage informatics platform for high-throughput embryo phenotyping.

    Science.gov (United States)

    Brown, James M; Horner, Neil R; Lawson, Thomas N; Fiegel, Tanja; Greenaway, Simon; Morgan, Hugh; Ring, Natalie; Santos, Luis; Sneddon, Duncan; Teboul, Lydia; Vibert, Jennifer; Yaikhom, Gagarine; Westerberg, Henrik; Mallon, Ann-Marie

    2018-01-01

    High-throughput phenotyping is a cornerstone of numerous functional genomics projects. In recent years, imaging screens have become increasingly important in understanding gene-phenotype relationships in studies of cells, tissues and whole organisms. Three-dimensional (3D) imaging has risen to prominence in the field of developmental biology for its ability to capture whole embryo morphology and gene expression, as exemplified by the International Mouse Phenotyping Consortium (IMPC). Large volumes of image data are being acquired by multiple institutions around the world that encompass a range of modalities, proprietary software and metadata. To facilitate robust downstream analysis, images and metadata must be standardized to account for these differences. As an open scientific enterprise, making the data readily accessible is essential so that members of biomedical and clinical research communities can study the images for themselves without the need for highly specialized software or technical expertise. In this article, we present a platform of software tools that facilitate the upload, analysis and dissemination of 3D images for the IMPC. Over 750 reconstructions from 80 embryonic lethal and subviable lines have been captured to date, all of which are openly accessible at mousephenotype.org. Although designed for the IMPC, all software is available under an open-source licence for others to use and develop further. Ongoing developments aim to increase throughput and improve the analysis and dissemination of image data. Furthermore, we aim to ensure that images are searchable so that users can locate relevant images associated with genes, phenotypes or human diseases of interest. © The Author 2016. Published by Oxford University Press.

  10. High-Throughput Next-Generation Sequencing of Polioviruses

    Science.gov (United States)

    Montmayeur, Anna M.; Schmidt, Alexander; Zhao, Kun; Magaña, Laura; Iber, Jane; Castro, Christina J.; Chen, Qi; Henderson, Elizabeth; Ramos, Edward; Shaw, Jing; Tatusov, Roman L.; Dybdahl-Sissoko, Naomi; Endegue-Zanga, Marie Claire; Adeniji, Johnson A.; Oberste, M. Steven; Burns, Cara C.

    2016-01-01

    ABSTRACT The poliovirus (PV) is currently targeted for worldwide eradication and containment. Sanger-based sequencing of the viral protein 1 (VP1) capsid region is currently the standard method for PV surveillance. However, the whole-genome sequence is sometimes needed for higher resolution global surveillance. In this study, we optimized whole-genome sequencing protocols for poliovirus isolates and FTA cards using next-generation sequencing (NGS), aiming for high sequence coverage, efficiency, and throughput. We found that DNase treatment of poliovirus RNA followed by random reverse transcription (RT), amplification, and the use of the Nextera XT DNA library preparation kit produced significantly better results than other preparations. The average viral reads per total reads, a measurement of efficiency, was as high as 84.2% ± 15.6%. PV genomes covering >99 to 100% of the reference length were obtained and validated with Sanger sequencing. A total of 52 PV genomes were generated, multiplexing as many as 64 samples in a single Illumina MiSeq run. This high-throughput, sequence-independent NGS approach facilitated the detection of a diverse range of PVs, especially for those in vaccine-derived polioviruses (VDPV), circulating VDPV, or immunodeficiency-related VDPV. In contrast to results from previous studies on other viruses, our results showed that filtration and nuclease treatment did not discernibly increase the sequencing efficiency of PV isolates. However, DNase treatment after nucleic acid extraction to remove host DNA significantly improved the sequencing results. This NGS method has been successfully implemented to generate PV genomes for molecular epidemiology of the most recent PV isolates. Additionally, the ability to obtain full PV genomes from FTA cards will aid in facilitating global poliovirus surveillance. PMID:27927929

  11. Maximizing gain in high-throughput screening using conformal prediction.

    Science.gov (United States)

    Svensson, Fredrik; Afzal, Avid M; Norinder, Ulf; Bender, Andreas

    2018-02-21

    Iterative screening has emerged as a promising approach to increase the efficiency of screening campaigns compared to traditional high throughput approaches. By learning from a subset of the compound library, inferences on what compounds to screen next can be made by predictive models, resulting in more efficient screening. One way to evaluate screening is to consider the cost of screening compared to the gain associated with finding an active compound. In this work, we introduce a conformal predictor coupled with a gain-cost function with the aim to maximise gain in iterative screening. Using this setup we were able to show that by evaluating the predictions on the training data, very accurate predictions on what settings will produce the highest gain on the test data can be made. We evaluate the approach on 12 bioactivity datasets from PubChem training the models using 20% of the data. Depending on the settings of the gain-cost function, the settings generating the maximum gain were accurately identified in 8-10 out of the 12 datasets. Broadly, our approach can predict what strategy generates the highest gain based on the results of the cost-gain evaluation: to screen the compounds predicted to be active, to screen all the remaining data, or not to screen any additional compounds. When the algorithm indicates that the predicted active compounds should be screened, our approach also indicates what confidence level to apply in order to maximize gain. Hence, our approach facilitates decision-making and allocation of the resources where they deliver the most value by indicating in advance the likely outcome of a screening campaign.

  12. Scanning fluorescence detector for high-throughput DNA genotyping

    Science.gov (United States)

    Rusch, Terry L.; Petsinger, Jeremy; Christensen, Carl; Vaske, David A.; Brumley, Robert L., Jr.; Luckey, John A.; Weber, James L.

    1996-04-01

    A new scanning fluorescence detector (SCAFUD) was developed for high-throughput genotyping of short tandem repeat polymorphisms (STRPs). Fluorescent dyes are incorporated into relatively short DNA fragments via polymerase chain reaction (PCR) and are separated by electrophoresis in short, wide polyacrylamide gels (144 lanes with well to read distances of 14 cm). Excitation light from an argon laser with primary lines at 488 and 514 nm is introduced into the gel through a fiber optic cable, dichroic mirror, and 40X microscope objective. Emitted fluorescent light is collected confocally through a second fiber. The confocal head is translated across the bottom of the gel at 0.5 Hz. The detection unit utilizes dichroic mirrors and band pass filters to direct light with 10 - 20 nm bandwidths to four photomultiplier tubes (PMTs). PMT signals are independently amplified with variable gain and then sampled at a rate of 2500 points per scan using a computer based A/D board. LabView software (National Instruments) is used for instrument operation. Currently, three fluorescent dyes (Fam, Hex and Rox) are simultaneously detected with peak detection wavelengths of 543, 567, and 613 nm, respectively. The detection limit for fluorescein-labeled primers is about 100 attomoles. Planned SCAFUD upgrades include rearrangement of laser head geometry, use of additional excitation lasers for simultaneous detection of more dyes, and the use of detector arrays instead of individual PMTs. Extensive software has been written for automatic analysis of SCAFUD images. The software enables background subtraction, band identification, multiple- dye signal resolution, lane finding, band sizing and allele calling. Whole genome screens are currently underway to search for loci influencing such complex diseases as diabetes, asthma, and hypertension. Seven production SCAFUDs are currently in operation. Genotyping output for the coming year is projected to be about one million total genotypes (DNA

  13. Development of a high throughput single-particle screening for inorganic semiconductor nanorods as neural voltage sensor

    Science.gov (United States)

    Kuo, Yung; Park, Kyoungwon; Li, Jack; Ingargiola, Antonino; Park, Joonhyuck; Shvadchak, Volodymyr; Weiss, Shimon

    2017-08-01

    Monitoring membrane potential in neurons requires sensors with minimal invasiveness, high spatial and temporal (sub-ms) resolution, and large sensitivity for enabling detection of sub-threshold activities. While organic dyes and fluorescent proteins have been developed to possess voltage-sensing properties, photobleaching, cytotoxicity, low sensitivity, and low spatial resolution have obstructed further studies. Semiconductor nanoparticles (NPs), as prospective voltage sensors, have shown excellent sensitivity based on Quantum confined Stark effect (QCSE) at room temperature and at single particle level. Both theory and experiment have shown their voltage sensitivity can be increased significantly via material, bandgap, and structural engineering. Based on theoretical calculations, we synthesized one of the optimal candidates for voltage sensors: 12 nm type-II ZnSe/CdS nanorods (NRs), with an asymmetrically located seed. The voltage sensitivity and spectral shift were characterized in vitro using spectrally-resolved microscopy using electrodes grown by thin film deposition, which "sandwich" the NRs. We characterized multiple batches of such NRs and iteratively modified the synthesis to achieve higher voltage sensitivity (ΔF/F> 10%), larger spectral shift (>5 nm), better homogeneity, and better colloidal stability. Using a high throughput screening method, we were able to compare the voltage sensitivity of our NRs with commercial spherical quantum dots (QDs) with single particle statistics. Our method of high throughput screening with spectrally-resolved microscope also provides a versatile tool for studying single particles spectroscopy under field modulation.

  14. Quantum Chemistry, and Eclectic Mix: From Silicon Carbide to Size Consistency

    Energy Technology Data Exchange (ETDEWEB)

    Rintelman, Jamie Marie [Iowa State Univ., Ames, IA (United States)

    2004-12-19

    Chemistry is a field of great breadth and variety. It is this diversity that makes for both an interesting and challenging field. My interests have spanned three major areas of theoretical chemistry: applications, method development, and method evaluation. The topics presented in this thesis are as follows: (1) a multi-reference study of the geometries and relative energies of four atom silicon carbide clusters in the gas phase; (2) the reaction of acetylene on the Si(100)-(2x1) surface; (3) an improvement to the Effective Fragment Potential (EFP) solvent model to enable the study of reactions in both aqueous and nonaqueous solution; and (4) an evaluation of the size consistency of Multireference Perturbation Theory (MRPT). In the following section, the author briefly discusses two topics central to, and present throughout, this thesis: Multi-reference methods and Quantum Mechanics/Molecular Mechanics (QM/MM) methods.

  15. High throughput, low set-up time reconfigurable linear feedback shift registers

    NARCIS (Netherlands)

    Nas, R.J.M.; Berkel, van C.H.

    2010-01-01

    This paper presents a hardware design for a scalable, high throughput, configurable LFSR. High throughput is achieved by producing L consecutive outputs per clock cycle with a clock cycle period that, for practical cases, increases only logarithmically with the block size L and the length of the

  16. 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...

  17. Alginate Immobilization of Metabolic Enzymes (AIME) for High-Throughput Screening Assays (SOT)

    Science.gov (United States)

    Alginate Immobilization of Metabolic Enzymes (AIME) for High-Throughput Screening Assays DE DeGroot, RS Thomas, and SO SimmonsNational Center for Computational Toxicology, US EPA, Research Triangle Park, NC USAThe EPA’s ToxCast program utilizes a wide variety of high-throughput s...

  18. The surface chemistry determines the spatio-temporal interaction dynamics of quantum dots in atherosclerotic lesions.

    Science.gov (United States)

    Uhl, Bernd; Hirn, Stephanie; Mildner, Karina; Coletti, Raffaele; Massberg, Steffen; Reichel, Christoph A; Rehberg, Markus; Zeuschner, Dagmar; Krombach, Fritz

    2018-03-01

    To optimize the design of nanoparticles for diagnosis or therapy of vascular diseases, it is mandatory to characterize the determinants of nano-bio interactions in vascular lesions. Using ex vivo and in vivo microscopy, we analyzed the interactive behavior of quantum dots with different surface functionalizations in atherosclerotic lesions of ApoE-deficient mice. We demonstrate that quantum dots with different surface functionalizations exhibit specific interactive behaviors with distinct molecular and cellular components of the injured vessel wall. Moreover, we show a role for fibrinogen in the regulation of the spatio-temporal interaction dynamics in atherosclerotic lesions. Our findings emphasize the relevance of surface chemistry-driven nano-bio interactions on the differential in vivo behavior of nanoparticles in diseased tissue.

  19. Advanced high throughput MOX fuel fabrication technology and sustainable development

    International Nuclear Information System (INIS)

    Krellmann, Juergen

    2005-01-01

    The MELOX plant in the south of France together with the La Hague reprocessing plant, are part of the two industrial facilities in charge of closing the nuclear fuel cycle in France. Started up in 1995, MELOX has since accumulated a solid know-how in recycling plutonium recovered from spent uranium fuel into MOX: a fuel blend comprised of both uranium and plutonium oxides. Converting recovered Pu into a proliferation-resistant material that can readily be used to power a civil nuclear reactor, MOX fabrication offers a sustainable solution to safely take advantage of the plutonium's high energy content. Being the first large-capacity industrial facility dedicated to MOX fuel fabrication, MELOX distinguishes itself from the first generation MOX plants with high capacity (around 200 tHM versus around 40 tHM) and several unique operational features designed to improve productivity, reliability and flexibility while maintaining high safety standards. Providing an exemplary reference for high throughput MOX fabrication with 1,000 tHM produced since start-up, the unique process and technologies implemented at MELOX are currently inspiring other MOX plant construction projects (in Japan with the J-MOX plant, in the US and in Russia as part of the weapon-grade plutonium inventory reduction). Spurred by the growing international demand, MELOX has embarked upon an ambitious production development and diversification plan. Starting from an annual level of 100 tons of heavy metal (tHM), MELOX demonstrated production capacity is continuously increasing: MELOX is now aiming for a minimum of 140 tHM by the end of 2005, with the ultimate ambition of reaching the full capacity of the plant (around 200 tHM) in the near future. With regards to its activity, MELOX also remains deeply committed to sustainable development in a consolidated involvement within AREVA group. The French minister of Industry, on August 26th 2005, acknowledged the benefits of MOX fuel production at MELOX: 'In

  20. High throughput comet assay to study genotoxicity of nanomaterials

    Directory of Open Access Journals (Sweden)

    Naouale El Yamani

    2015-06-01

    Full Text Available The unique physicochemical properties of engineered nanomaterials (NMs have accelerated their use in diverse industrial and domestic products. Although their presence in consumer products represents a major concern for public health safety, their potential impact on human health is poorly understood. There is therefore an urgent need to clarify the toxic effects of NMs and to elucidate the mechanisms involved. In view of the large number of NMs currently being used, high throughput (HTP screening technologies are clearly needed for efficient assessment of toxicity. The comet assay is the most used method in nanogenotoxicity studies and has great potential for increasing throughput as it is fast, versatile and robust; simple technical modifications of the assay make it possible to test many compounds (NMs in a single experiment. The standard gel of 70-100 μL contains thousands of cells, of which only a tiny fraction are actually scored. Reducing the gel to a volume of 5 μL, with just a few hundred cells, allows twelve gels to be set on a standard slide, or 96 as a standard 8x12 array. For the 12 gel format, standard slides precoated with agarose are placed on a metal template and gels are set on the positions marked on the template. The HTP comet assay, incorporating digestion of DNA with formamidopyrimidine DNA glycosylase (FPG to detect oxidised purines, has recently been applied to study the potential induction of genotoxicity by NMs via reactive oxygen. In the NanoTEST project we investigated the genotoxic potential of several well-characterized metal and polymeric nanoparticles with the comet assay. All in vitro studies were harmonized; i.e. NMs were from the same batch, and identical dispersion protocols, exposure time, concentration range, culture conditions, and time-courses were used. As a kidney model, Cos-1 fibroblast-like kidney cells were treated with different concentrations of iron oxide NMs, and cells embedded in minigels (12

  1. High-throughput peptide mass fingerprinting and protein macroarray analysis using chemical printing strategies

    International Nuclear Information System (INIS)

    Sloane, A.J.; Duff, J.L.; Hopwood, F.G.; Wilson, N.L.; Smith, P.E.; Hill, C.J.; Packer, N.H.; Williams, K.L.; Gooley, A.A.; Cole, R.A.; Cooley, P.W.; Wallace, D.B.

    2001-01-01

    We describe a 'chemical printer' that uses piezoelectric pulsing for rapid and accurate microdispensing of picolitre volumes of fluid for proteomic analysis of 'protein macroarrays'. Unlike positive transfer and pin transfer systems, our printer dispenses fluid in a non-contact process that ensures that the fluid source cannot be contaminated by substrate during a printing event. We demonstrate automated delivery of enzyme and matrix solutions for on-membrane protein digestion and subsequent peptide mass fingerprinting (pmf) analysis directly from the membrane surface using matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). This approach bypasses the more commonly used multi-step procedures, thereby permitting a more rapid procedure for protein identification. We also highlight the advantage of printing different chemistries onto an individual protein spot for multiple microscale analyses. This ability is particularly useful when detailed characterisation of rare and valuable sample is required. Using a combination of PNGase F and trypsin we have mapped sites of N-glycosylation using on-membrane digestion strategies. We also demonstrate the ability to print multiple serum samples in a micro-ELISA format and rapidly screen a protein macroarray of human blood plasma for pathogen-derived antigens. We anticipate that the 'chemical printer' will be a major component of proteomic platforms for high-throughput protein identification and characterisation with widespread applications in biomedical and diagnostic discovery

  2. Surface Plasmon Resonance: New Biointerface Designs and High-Throughput Affinity Screening

    Science.gov (United States)

    Linman, Matthew J.; Cheng, Quan Jason

    Surface plasmon resonance (SPR) is a surface optical technique that measures minute changes in refractive index at a metal-coated surface. It has become increasingly popular in the study of biological and chemical analytes because of its label-free measurement feature. In addition, SPR allows for both quantitative and qualitative assessment of binding interactions in real time, making it ideally suited for probing weak interactions that are often difficult to study with other methods. This chapter presents the biosensor development in the last 3 years or so utilizing SPR as the principal analytical technique, along with a concise background of the technique itself. While SPR has demonstrated many advantages, it is a nonselective method and so, building reproducible and functional interfaces is vital to sensing applications. This chapter, therefore, focuses mainly on unique surface chemistries and assay approaches to examine biological interactions with SPR. In addition, SPR imaging for high-throughput screening based on microarrays and novel hyphenated techniques involving the coupling of SPR to other analytical methods is discussed. The chapter concludes with a commentary on the current state of SPR biosensing technology and the general direction of future biosensor research.

  3. Introducing Discrete Frequency Infrared Technology for High-Throughput Biofluid Screening

    Science.gov (United States)

    Hughes, Caryn; Clemens, Graeme; Bird, Benjamin; Dawson, Timothy; Ashton, Katherine M.; Jenkinson, Michael D.; Brodbelt, Andrew; Weida, Miles; Fotheringham, Edeline; Barre, Matthew; Rowlette, Jeremy; Baker, Matthew J.

    2016-02-01

    Accurate early diagnosis is critical to patient survival, management and quality of life. Biofluids are key to early diagnosis due to their ease of collection and intimate involvement in human function. Large-scale mid-IR imaging of dried fluid deposits offers a high-throughput molecular analysis paradigm for the biomedical laboratory. The exciting advent of tuneable quantum cascade lasers allows for the collection of discrete frequency infrared data enabling clinically relevant timescales. By scanning targeted frequencies spectral quality, reproducibility and diagnostic potential can be maintained while significantly reducing acquisition time and processing requirements, sampling 16 serum spots with 0.6, 5.1 and 15% relative standard deviation (RSD) for 199, 14 and 9 discrete frequencies respectively. We use this reproducible methodology to show proof of concept rapid diagnostics; 40 unique dried liquid biopsies from brain, breast, lung and skin cancer patients were classified in 2.4 cumulative seconds against 10 non-cancer controls with accuracies of up to 90%.

  4. Analysis of temporal evolution of quantum dot surface chemistry by surface-enhanced Raman scattering.

    Science.gov (United States)

    Doğan, İlker; Gresback, Ryan; Nozaki, Tomohiro; van de Sanden, Mauritius C M

    2016-07-08

    Temporal evolution of surface chemistry during oxidation of silicon quantum dot (Si-QD) surfaces were probed using surface-enhanced Raman scattering (SERS). A monolayer of hydrogen and chlorine terminated plasma-synthesized Si-QDs were spin-coated on silver oxide thin films. A clearly enhanced signal of surface modes, including Si-Clx and Si-Hx modes were observed from as-synthesized Si-QDs as a result of the plasmonic enhancement of the Raman signal at Si-QD/silver oxide interface. Upon oxidation, a gradual decrease of Si-Clx and Si-Hx modes, and an emergence of Si-Ox and Si-O-Hx modes have been observed. In addition, first, second and third transverse optical modes of Si-QDs were also observed in the SERS spectra, revealing information on the crystalline morphology of Si-QDs. An absence of any of the abovementioned spectral features, but only the first transverse optical mode of Si-QDs from thick Si-QD films validated that the spectral features observed from Si-QDs on silver oxide thin films are originated from the SERS effect. These results indicate that real-time SERS is a powerful diagnostic tool and a novel approach to probe the dynamic surface/interface chemistry of quantum dots, especially when they involve in oxidative, catalytic, and electrochemical surface/interface reactions.

  5. High-throughput on-chip in vivo neural regeneration studies using femtosecond laser nano-surgery and microfluidics

    Science.gov (United States)

    Rohde, Christopher B.; Zeng, Fei; Gilleland, Cody; Samara, Chrysanthi; Yanik, Mehmet F.

    2009-02-01

    In recent years, the advantages of using small invertebrate animals as model systems for human disease have become increasingly apparent and have resulted in three Nobel Prizes in medicine or chemistry during the last six years for studies conducted on the nematode Caenorhabditis elegans (C. elegans). The availability of a wide array of species-specific genetic techniques, along with the transparency of the worm and its ability to grow in minute volumes make C. elegans an extremely powerful model organism. We present a suite of technologies for complex high-throughput whole-animal genetic and drug screens. We demonstrate a high-speed microfluidic sorter that can isolate and immobilize C. elegans in a well-defined geometry, an integrated chip containing individually addressable screening chambers for incubation and exposure of individual animals to biochemical compounds, and a device for delivery of compound libraries in standard multiwell plates to microfluidic devices. The immobilization stability obtained by these devices is comparable to that of chemical anesthesia and the immobilization process does not affect lifespan, progeny production, or other aspects of animal health. The high-stability enables the use of a variety of key optical techniques. We use this to demonstrate femtosecond-laser nanosurgery and three-dimensional multiphoton microscopy. Used alone or in various combinations these devices facilitate a variety of high-throughput assays using whole animals, including mutagenesis and RNAi and drug screens at subcellular resolution, as well as high-throughput high-precision manipulations such as femtosecond-laser nanosurgery for large-scale in vivo neural degeneration and regeneration studies.

  6. Density functional representation of quantum chemistry. II. Local quantum field theories of molecular matter in terms of the charge density operator do not work

    International Nuclear Information System (INIS)

    Primas, H.; Schleicher, M.

    1975-01-01

    A comprehensive review of the attempts to rephrase molecular quantum mechanics in terms of the particle density operator and the current density or phase density operator is given. All pertinent investigations which have come to attention suffer from severe mathematical inconsistencies and are not adequate to the few-body problem of quantum chemistry. The origin of the failure of these attempts is investigated, and it is shown that a realization of a local quantum field theory of molecular matter in terms of observables would presuppose the solution of many highly nontrivial mathematical problems

  7. A Synthesis of Fluid Dynamics and Quantum Chemistry for the Design of Nanoelectronics

    Science.gov (United States)

    MacDougall, Preston J.

    1998-01-01

    In 1959, during a famous lecture entitled "There's Plenty of Room at the Bottom", Richard Feynman focused on the startling technical possibilities that would exist at the limit of miniaturization, that being atomically precise devices with dimensions in the nanometer range. A nanometer is both a convenient unit of length for medium to large sized molecules, and the root of the name of the new interdisciplinary field of "nanotechnology". Essentially, "nanoelectronics" denotes the goal of shrinking electronic devices, such as diodes and transistors, as well as integrated circuits of such devices that can perform logical operations, down to dimensions in the range of 100 nanometers. The thirty-year hiatus in the development of nanotechnology can figuratively be seen as a period of waiting for the bottom-up and atomically precise construction skills of synthetic chemistry to meet the top-down reductionist aspirations of device physics. The sub-nanometer domain of nineteenth-century classical chemistry has steadily grown, and state-of-the-art supramolecular chemistry can achieve atomic precision in non-repeating molecular assemblies of the size desired for nanotechnology. For nanoelectronics in particular, a basic understanding of the electron transport properties of molecules must also be developed. Quantum chemistry provides powerful computational methods that can accurately predict the properties of small to medium sized molecules on a desktop workstation, and those of large molecules if one has access to a supercomputer. Of the many properties of a molecule that quantum chemistry routinely predicts, the ability to carry a current is one that had not even been considered until recently. "Currently", there is a controversy over just how to define this key property. Reminiscent of the situation in high-Tc superconductivity, much of the difficulty arises from the different models that are used to simplify the complex electronic structure of real materials. A model

  8. Parallel algorithms for quantum chemistry. I. Integral transformations on a hypercube multiprocessor

    International Nuclear Information System (INIS)

    Whiteside, R.A.; Binkley, J.S.; Colvin, M.E.; Schaefer, H.F. III

    1987-01-01

    For many years it has been recognized that fundamental physical constraints such as the speed of light will limit the ultimate speed of single processor computers to less than about three billion floating point operations per second (3 GFLOPS). This limitation is becoming increasingly restrictive as commercially available machines are now within an order of magnitude of this asymptotic limit. A natural way to avoid this limit is to harness together many processors to work on a single computational problem. In principle, these parallel processing computers have speeds limited only by the number of processors one chooses to acquire. The usefulness of potentially unlimited processing speed to a computationally intensive field such as quantum chemistry is obvious. If these methods are to be applied to significantly larger chemical systems, parallel schemes will have to be employed. For this reason we have developed distributed-memory algorithms for a number of standard quantum chemical methods. We are currently implementing these on a 32 processor Intel hypercube. In this paper we present our algorithm and benchmark results for one of the bottleneck steps in quantum chemical calculations: the four index integral transformation

  9. A high-throughput reactor system for optimization of Mo–V–Nb mixed oxide catalyst composition in ethane ODH

    KAUST Repository

    Zhu, Haibo; Laveille, Paco; Rosenfeld, Devon C.; Hedhili, Mohamed N.; Basset, Jean-Marie

    2015-01-01

    75 Mo-V-Nb mixed oxide catalysts with a broad range of compositions were prepared by a simple evaporation method, and were screened for the ethane oxidative dehydrogenation (ODH) reaction. The compositions of these 75 catalysts were systematically changed by varying the Nb loading, and the Mo/V molar ratio. Characterization by XRD, XPS, H2-TPR and SEM revealed that an intimate structure is formed among the 3 components. The strong interaction among different components leads to the formation of a new phase or an "intimate structure". The dependency of conversion and selectivity on the catalyst composition was clearly demonstrated from the results of high-throughput testing. The optimized Mo-V-Nb molar composition was confirmed to be composed of a Nb content of 4-8%, a Mo content of 70-83%, and a V content of 12-25%. The enhanced catalytic performance of the mixed oxides is obviously due to the synergistic effects of the different components. The optimized compositions for ethane ODH revealed in our high-throughput tests and the structural information provided by our characterization studies can serve as the starting point for future efforts to improve the catalytic performance of Mo-V-Nb oxides. This journal is © The Royal Society of Chemistry.

  10. Lateral Temperature-Gradient Method for High-Throughput Characterization of Material Processing by Millisecond Laser Annealing.

    Science.gov (United States)

    Bell, Robert T; Jacobs, Alan G; Sorg, Victoria C; Jung, Byungki; Hill, Megan O; Treml, Benjamin E; Thompson, Michael O

    2016-09-12

    A high-throughput method for characterizing the temperature dependence of material properties following microsecond to millisecond thermal annealing, exploiting the temperature gradients created by a lateral gradient laser spike anneal (lgLSA), is presented. Laser scans generate spatial thermal gradients of up to 5 °C/μm with peak temperatures ranging from ambient to in excess of 1400 °C, limited only by laser power and materials thermal limits. Discrete spatial property measurements across the temperature gradient are then equivalent to independent measurements after varying temperature anneals. Accurate temperature calibrations, essential to quantitative analysis, are critical and methods for both peak temperature and spatial/temporal temperature profile characterization are presented. These include absolute temperature calibrations based on melting and thermal decomposition, and time-resolved profiles measured using platinum thermistors. A variety of spatially resolved measurement probes, ranging from point-like continuous profiling to large area sampling, are discussed. Examples from annealing of III-V semiconductors, CdSe quantum dots, low-κ dielectrics, and block copolymers are included to demonstrate the flexibility, high throughput, and precision of this technique.

  11. A method for high throughput bioelectrochemical research based on small scale microbial electrolysis cells

    KAUST Repository

    Call, Douglas F.; Logan, Bruce E.

    2011-01-01

    There is great interest in studying exoelectrogenic microorganisms, but existing methods can require expensive electrochemical equipment and specialized reactors. We developed a simple system for conducting high throughput bioelectrochemical

  12. DRABAL: novel method to mine large high-throughput screening assays using Bayesian active learning

    KAUST Repository

    Soufan, Othman; Ba Alawi, Wail; Afeef, Moataz A.; Essack, Magbubah; Kalnis, Panos; Bajic, Vladimir B.

    2016-01-01

    Mining high-throughput screening (HTS) assays is key for enhancing decisions in the area of drug repositioning and drug discovery. However, many challenges are encountered in the process of developing suitable and accurate methods

  13. Computational and statistical methods for high-throughput mass spectrometry-based PTM analysis

    DEFF Research Database (Denmark)

    Schwämmle, Veit; Vaudel, Marc

    2017-01-01

    Cell signaling and functions heavily rely on post-translational modifications (PTMs) of proteins. Their high-throughput characterization is thus of utmost interest for multiple biological and medical investigations. In combination with efficient enrichment methods, peptide mass spectrometry analy...

  14. EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES

    Science.gov (United States)

    Embryonic vascular disruption is an important adverse outcome pathway (AOP) given the knowledge that chemical disruption of early cardiovascular system development leads to broad prenatal defects. High throughput screening (HTS) assays provide potential building blocks for AOP d...

  15. Applications of high-throughput sequencing to chromatin structure and function in mammals

    OpenAIRE

    Dunham, Ian

    2009-01-01

    High-throughput DNA sequencing approaches have enabled direct interrogation of chromatin samples from mammalian cells. We are beginning to develop a genome-wide description of nuclear function during development, but further data collection, refinement, and integration are needed.

  16. Data for automated, high-throughput microscopy analysis of intracellular bacterial colonies using spot detection

    DEFF Research Database (Denmark)

    Ernstsen, Christina Lundgaard; Login, Frédéric H.; Jensen, Helene Halkjær

    2017-01-01

    Quantification of intracellular bacterial colonies is useful in strategies directed against bacterial attachment, subsequent cellular invasion and intracellular proliferation. An automated, high-throughput microscopy-method was established to quantify the number and size of intracellular bacteria...

  17. Coupled effects of solution chemistry and hydrodynamics on the mobility and transport of quantum dot nanomaterials in the Vadose Zone

    Science.gov (United States)

    To investigate the coupled effects of solution chemistry and vadose zone processes on the mobility of quantum dot (QD) nanoparticles, laboratory scale transport experiments were performed. The complex coupled effects of ionic strength, size of QD aggregates, surface tension, contact angle, infiltrat...

  18. A high throughput platform for understanding the influence of excipients on physical and chemical stability

    DEFF Research Database (Denmark)

    Raijada, Dhara; Cornett, Claus; Rantanen, Jukka

    2013-01-01

    The present study puts forward a miniaturized high-throughput platform to understand influence of excipient selection and processing on the stability of a given drug compound. Four model drugs (sodium naproxen, theophylline, amlodipine besylate and nitrofurantoin) and ten different excipients were...... for chemical degradation. The proposed high-throughput platform can be used during early drug development to simulate typical processing induced stress in a small scale and to understand possible phase transformation behaviour and influence of excipients on this....

  19. Application of high-throughput sequencing in understanding human oral microbiome related with health and disease

    OpenAIRE

    Chen, Hui; Jiang, Wen

    2014-01-01

    The oral microbiome is one of most diversity habitat in the human body and they are closely related with oral health and disease. As the technique developing,, high throughput sequencing has become a popular approach applied for oral microbial analysis. Oral bacterial profiles have been studied to explore the relationship between microbial diversity and oral diseases such as caries and periodontal disease. This review describes the application of high-throughput sequencing for characterizati...

  20. Multireference quantum chemistry through a joint density matrix renormalization group and canonical transformation theory.

    Science.gov (United States)

    Yanai, Takeshi; Kurashige, Yuki; Neuscamman, Eric; Chan, Garnet Kin-Lic

    2010-01-14

    We describe the joint application of the density matrix renormalization group and canonical transformation theory to multireference quantum chemistry. The density matrix renormalization group provides the ability to describe static correlation in large active spaces, while the canonical transformation theory provides a high-order description of the dynamic correlation effects. We demonstrate the joint theory in two benchmark systems designed to test the dynamic and static correlation capabilities of the methods, namely, (i) total correlation energies in long polyenes and (ii) the isomerization curve of the [Cu(2)O(2)](2+) core. The largest complete active spaces and atomic orbital basis sets treated by the joint DMRG-CT theory in these systems correspond to a (24e,24o) active space and 268 atomic orbitals in the polyenes and a (28e,32o) active space and 278 atomic orbitals in [Cu(2)O(2)](2+).

  1. The Quixote project: Collaborative and Open Quantum Chemistry data management in the Internet age.

    Science.gov (United States)

    Adams, Sam; de Castro, Pablo; Echenique, Pablo; Estrada, Jorge; Hanwell, Marcus D; Murray-Rust, Peter; Sherwood, Paul; Thomas, Jens; Townsend, Joe

    2011-10-14

    Computational Quantum Chemistry has developed into a powerful, efficient, reliable and increasingly routine tool for exploring the structure and properties of small to medium sized molecules. Many thousands of calculations are performed every day, some offering results which approach experimental accuracy. However, in contrast to other disciplines, such as crystallography, or bioinformatics, where standard formats and well-known, unified databases exist, this QC data is generally destined to remain locally held in files which are not designed to be machine-readable. Only a very small subset of these results will become accessible to the wider community through publication.In this paper we describe how the Quixote Project is developing the infrastructure required to convert output from a number of different molecular quantum chemistry packages to a common semantically rich, machine-readable format and to build respositories of QC results. Such an infrastructure offers benefits at many levels. The standardised representation of the results will facilitate software interoperability, for example making it easier for analysis tools to take data from different QC packages, and will also help with archival and deposition of results. The repository infrastructure, which is lightweight and built using Open software components, can be implemented at individual researcher, project, organisation or community level, offering the exciting possibility that in future many of these QC results can be made publically available, to be searched and interpreted just as crystallography and bioinformatics results are today.Although we believe that quantum chemists will appreciate the contribution the Quixote infrastructure can make to the organisation and and exchange of their results, we anticipate that greater rewards will come from enabling their results to be consumed by a wider community. As the respositories grow they will become a valuable source of chemical data for use by other

  2. The Quixote project: Collaborative and Open Quantum Chemistry data management in the Internet age

    Directory of Open Access Journals (Sweden)

    Adams Sam

    2011-10-01

    Full Text Available Abstract Computational Quantum Chemistry has developed into a powerful, efficient, reliable and increasingly routine tool for exploring the structure and properties of small to medium sized molecules. Many thousands of calculations are performed every day, some offering results which approach experimental accuracy. However, in contrast to other disciplines, such as crystallography, or bioinformatics, where standard formats and well-known, unified databases exist, this QC data is generally destined to remain locally held in files which are not designed to be machine-readable. Only a very small subset of these results will become accessible to the wider community through publication. In this paper we describe how the Quixote Project is developing the infrastructure required to convert output from a number of different molecular quantum chemistry packages to a common semantically rich, machine-readable format and to build respositories of QC results. Such an infrastructure offers benefits at many levels. The standardised representation of the results will facilitate software interoperability, for example making it easier for analysis tools to take data from different QC packages, and will also help with archival and deposition of results. The repository infrastructure, which is lightweight and built using Open software components, can be implemented at individual researcher, project, organisation or community level, offering the exciting possibility that in future many of these QC results can be made publically available, to be searched and interpreted just as crystallography and bioinformatics results are today. Although we believe that quantum chemists will appreciate the contribution the Quixote infrastructure can make to the organisation and and exchange of their results, we anticipate that greater rewards will come from enabling their results to be consumed by a wider community. As the respositories grow they will become a valuable source of

  3. Screening small-molecule compound microarrays for protein ligands without fluorescence labeling with a high-throughput scanning microscope.

    Science.gov (United States)

    Fei, Yiyan; Landry, James P; Sun, Yungshin; Zhu, Xiangdong; Wang, Xiaobing; Luo, Juntao; Wu, Chun-Yi; Lam, Kit S

    2010-01-01

    We describe a high-throughput scanning optical microscope for detecting small-molecule compound microarrays on functionalized glass slides. It is based on measurements of oblique-incidence reflectivity difference and employs a combination of a y-scan galvometer mirror and an x-scan translation stage with an effective field of view of 2 cm x 4 cm. Such a field of view can accommodate a printed small-molecule compound microarray with as many as 10,000 to 20,000 targets. The scanning microscope is capable of measuring kinetics as well as endpoints of protein-ligand reactions simultaneously. We present the experimental results on solution-phase protein reactions with small-molecule compound microarrays synthesized from one-bead, one-compound combinatorial chemistry and immobilized on a streptavidin-functionalized glass slide.

  4. Identification of Rift Valley fever virus nucleocapsid protein-RNA binding inhibitors using a high-throughput screening assay.

    Science.gov (United States)

    Ellenbecker, Mary; Lanchy, Jean-Marc; Lodmell, J Stephen

    2012-09-01

    Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. Currently, there is no proven effective treatment for RVFV infection, and there is no licensed vaccine. Inhibition of RNA binding to the essential viral nucleocapsid (N) protein represents a potential antiviral therapeutic strategy because all of the functions performed by N during infection involve RNA binding. To target this interaction, we developed a fluorescence polarization-based high-throughput drug-screening assay and tested 26 424 chemical compounds for their ability to disrupt an N-RNA complex. From libraries of Food and Drug Administration-approved drugs, druglike molecules, and natural product extracts, we identified several lead compounds that are promising candidates for medicinal chemistry.

  5. Development of a Rapid Fluorescence-Based High-Throughput Screening Assay to Identify Novel Kynurenine 3-Monooxygenase Inhibitor Scaffolds.

    Science.gov (United States)

    Jacobs, K R; Guillemin, G J; Lovejoy, D B

    2018-02-01

    Kynurenine 3-monooxygenase (KMO) is a well-validated therapeutic target for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD) and Huntington's disease (HD). This work reports a facile fluorescence-based KMO assay optimized for high-throughput screening (HTS) that achieves a throughput approximately 20-fold higher than the fastest KMO assay currently reported. The screen was run with excellent performance (average Z' value of 0.80) from 110,000 compounds across 341 plates and exceeded all statistical parameters used to describe a robust HTS assay. A subset of molecules was selected for validation by ultra-high-performance liquid chromatography, resulting in the confirmation of a novel hit with an IC 50 comparable to that of the well-described KMO inhibitor Ro-61-8048. A medicinal chemistry program is currently underway to further develop our novel KMO inhibitor scaffolds.

  6. "One-sample concept" micro-combinatory for high throughput TEM of binary films.

    Science.gov (United States)

    Sáfrán, György

    2018-04-01

    Phases of thin films may remarkably differ from that of bulk. Unlike to the comprehensive data files of Binary Phase Diagrams [1] available for bulk, complete phase maps for thin binary layers do not exist. This is due to both the diverse metastable, non-equilibrium or instable phases feasible in thin films and the required volume of characterization work with analytical techniques like TEM, SAED and EDS. The aim of the present work was to develop a method that remarkably facilitates the TEM study of the diverse binary phases of thin films, or the creation of phase maps. A micro-combinatorial method was worked out that enables both preparation and study of a gradient two-component film within a single TEM specimen. For a demonstration of the technique thin Mn x Al 1- x binary samples with evolving concentration from x = 0 to x = 1 have been prepared so that the transition from pure Mn to pure Al covers a 1.5 mm long track within the 3 mm diameter TEM grid. The proposed method enables the preparation and study of thin combinatorial samples including all feasible phases as a function of composition or other deposition parameters. Contrary to known "combinatorial chemistry", in which a series of different samples are deposited in one run, and investigated, one at a time, the present micro-combinatorial method produces a single specimen condensing a complete library of a binary system that can be studied, efficiently, within a single TEM session. That provides extremely high throughput for TEM characterization of composition-dependent phases, exploration of new materials, or the construction of phase diagrams of binary films. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Technological Innovations for High-Throughput Approaches to In Vitro Allergy Diagnosis.

    Science.gov (United States)

    Chapman, Martin D; Wuenschmann, Sabina; King, Eva; Pomés, Anna

    2015-07-01

    Allergy diagnostics is being transformed by the advent of in vitro IgE testing using purified allergen molecules, combined with multiplex technology and biosensors, to deliver discriminating, sensitive, and high-throughput molecular diagnostics at the point of care. Essential elements of IgE molecular diagnostics are purified natural or recombinant allergens with defined purity and IgE reactivity, planar or bead-based multiplex systems to enable IgE to multiple allergens to be measured simultaneously, and, most recently, nanotechnology-based biosensors that facilitate rapid reaction rates and delivery of test results via mobile devices. Molecular diagnostics relies on measurement of IgE to purified allergens, the "active ingredients" of allergenic extracts. Typically, this involves measuring IgE to multiple allergens which is facilitated by multiplex technology and biosensors. The technology differentiates between clinically significant cross-reactive allergens (which could not be deduced by conventional IgE assays using allergenic extracts) and provides better diagnostic outcomes. Purified allergens are manufactured under good laboratory practice and validated using protein chemistry, mass spectrometry, and IgE antibody binding. Recently, multiple allergens (from dog) were expressed as a single molecule with high diagnostic efficacy. Challenges faced by molecular allergy diagnostic companies include generation of large panels of purified allergens with known diagnostic efficacy, access to flexible and robust array or sensor technology, and, importantly, access to well-defined serum panels form allergic patients for product development and validation. Innovations in IgE molecular diagnostics are rapidly being brought to market and will strengthen allergy testing at the point of care.

  8. GPU Linear Algebra Libraries and GPGPU Programming for Accelerating MOPAC Semiempirical Quantum Chemistry Calculations.

    Science.gov (United States)

    Maia, Julio Daniel Carvalho; Urquiza Carvalho, Gabriel Aires; Mangueira, Carlos Peixoto; Santana, Sidney Ramos; Cabral, Lucidio Anjos Formiga; Rocha, Gerd B

    2012-09-11

    In this study, we present some modifications in the semiempirical quantum chemistry MOPAC2009 code that accelerate single-point energy calculations (1SCF) of medium-size (up to 2500 atoms) molecular systems using GPU coprocessors and multithreaded shared-memory CPUs. Our modifications consisted of using a combination of highly optimized linear algebra libraries for both CPU (LAPACK and BLAS from Intel MKL) and GPU (MAGMA and CUBLAS) to hasten time-consuming parts of MOPAC such as the pseudodiagonalization, full diagonalization, and density matrix assembling. We have shown that it is possible to obtain large speedups just by using CPU serial linear algebra libraries in the MOPAC code. As a special case, we show a speedup of up to 14 times for a methanol simulation box containing 2400 atoms and 4800 basis functions, with even greater gains in performance when using multithreaded CPUs (2.1 times in relation to the single-threaded CPU code using linear algebra libraries) and GPUs (3.8 times). This degree of acceleration opens new perspectives for modeling larger structures which appear in inorganic chemistry (such as zeolites and MOFs), biochemistry (such as polysaccharides, small proteins, and DNA fragments), and materials science (such as nanotubes and fullerenes). In addition, we believe that this parallel (GPU-GPU) MOPAC code will make it feasible to use semiempirical methods in lengthy molecular simulations using both hybrid QM/MM and QM/QM potentials.

  9. Quantum chemistry calculation and experimental study on coal ash fusion characteristics of coal blend

    Energy Technology Data Exchange (ETDEWEB)

    Chen Yushuang; Zhang Zhong-xiao; Wu Xiao-jiang; Li Jie; Guang Rong-qing; Yan Bo [University of Shanghai for Science and Technology, Shanghai (China). Department of Power Engineering

    2009-07-01

    The coal ash fusion characteristics of high fusibility coal blending with two low fusibility coals respectively were studied. The data were analyzed using quantum chemistry methods and experiment from micro-and macro-molecular structures. The results show that Ca{sup 2+}, as the electron acceptor, easily enters into the lattice of mullite, causing a transition from mullite to anorthite. Mullite is much more stable than anorthite. Ca{sup 2+} of anorthite occupies the larger cavities with the (SiO{sub 4}){sup 4-} tetrahedral or (AlO{sub 4}){sup 5-} tetrahedral rings respectively. Ca atom linked O weakens Si-O bond, leading ash fusion point to reduce effectively. The chemistry, reactivity sites and bond-formation characteristics of minerals can well explain the reaction mechanism refractory minerals and flux ash melting process at high temperature. The results of experiment are agreed with the theory analysis by using ternary phase diagrams and quantitative calculation. 27 refs., 9 figs., 3 tabs.

  10. Automated chemical kinetic modeling via hybrid reactive molecular dynamics and quantum chemistry simulations.

    Science.gov (United States)

    Döntgen, Malte; Schmalz, Felix; Kopp, Wassja A; Kröger, Leif C; Leonhard, Kai

    2018-06-13

    An automated scheme for obtaining chemical kinetic models from scratch using reactive molecular dynamics and quantum chemistry simulations is presented. This methodology combines the phase space sampling of reactive molecular dynamics with the thermochemistry and kinetics prediction capabilities of quantum mechanics. This scheme provides the NASA polynomial and modified Arrhenius equation parameters for all species and reactions that are observed during the simulation and supplies them in the ChemKin format. The ab initio level of theory for predictions is easily exchangeable and the presently used G3MP2 level of theory is found to reliably reproduce hydrogen and methane oxidation thermochemistry and kinetics data. Chemical kinetic models obtained with this approach are ready-to-use for, e.g., ignition delay time simulations, as shown for hydrogen combustion. The presented extension of the ChemTraYzer approach can be used as a basis for methodologically advancing chemical kinetic modeling schemes and as a black-box approach to generate chemical kinetic models.

  11. High-throughput materials discovery and development: breakthroughs and challenges in the mapping of the materials genome

    Science.gov (United States)

    Buongiorno Nardelli, Marco

    High-Throughput Quantum-Mechanics computation of materials properties by ab initio methods has become the foundation of an effective approach to materials design, discovery and characterization. This data driven approach to materials science currently presents the most promising path to the development of advanced technological materials that could solve or mitigate important social and economic challenges of the 21st century. In particular, the rapid proliferation of computational data on materials properties presents the possibility to complement and extend materials property databases where the experimental data is lacking and difficult to obtain. Enhanced repositories such as AFLOWLIB open novel opportunities for structure discovery and optimization, including uncovering of unsuspected compounds, metastable structures and correlations between various properties. The practical realization of these opportunities depends almost exclusively on the the design of efficient algorithms for electronic structure simulations of realistic material systems beyond the limitations of the current standard theories. In this talk, I will review recent progress in theoretical and computational tools, and in particular, discuss the development and validation of novel functionals within Density Functional Theory and of local basis representations for effective ab-initio tight-binding schemes. Marco Buongiorno Nardelli is a pioneer in the development of computational platforms for theory/data/applications integration rooted in his profound and extensive expertise in the design of electronic structure codes and in his vision for sustainable and innovative software development for high-performance materials simulations. His research activities range from the design and discovery of novel materials for 21st century applications in renewable energy, environment, nano-electronics and devices, the development of advanced electronic structure theories and high-throughput techniques in

  12. The structural chemistry of metallocorroles: combined X-ray crystallography and quantum chemistry studies afford unique insights.

    Science.gov (United States)

    Thomas, Kolle E; Alemayehu, Abraham B; Conradie, Jeanet; Beavers, Christine M; Ghosh, Abhik

    2012-08-21

    Although they share some superficial structural similarities with porphyrins, corroles, trianionic ligands with contracted cores, give rise to fundamentally different transition metal complexes in comparison with the dianionic porphyrins. Many metallocorroles are formally high-valent, although a good fraction of them are also noninnocent, with significant corrole radical character. These electronic-structural characteristics result in a variety of fascinating spectroscopic behavior, including highly characteristic, paramagnetically shifted NMR spectra and textbook cases of charge-transfer spectra. Although our early research on corroles focused on spectroscopy, we soon learned that the geometric structures of metallocorroles provide a fascinating window into their electronic-structural characteristics. Thus, we used X-ray structure determinations and quantum chemical studies, chiefly using DFT, to obtain a comprehensive understanding of metallocorrole geometric and electronic structures. This Account describes our studies of the structural chemistry of metallocorroles. At first blush, the planar or mildly domed structure of metallocorroles might appear somewhat uninteresting particularly when compared to metalloporphyrins. Metalloporphyrins, especially sterically hindered ones, are routinely ruffled or saddled, but the missing meso carbon apparently makes the corrole skeleton much more resistant to nonplanar distortions. Ruffling, where the pyrrole rings are alternately twisted about the M-N bonds, is energetically impossible for metallocorroles. Saddling is also uncommon; thus, a number of sterically hindered, fully substituted metallocorroles exhibit almost perfectly planar macrocycle cores. Against this backdrop, copper corroles stand out as an important exception. As a result of an energetically favorable Cu(d(x2-y2))-corrole(π) orbital interaction, copper corroles, even sterically unhindered ones, are inherently saddled. Sterically hindered substituents

  13. Human Development VIII: A Theory of “Deep” Quantum Chemistry and Cell Consciousness: Quantum Chemistry Controls Genes and Biochemistry to Give Cells and Higher Organisms Consciousness and Complex Behavior

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2006-01-01

    Full Text Available Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it “sees”, and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occam’s razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules’ orbitals make one huge “cell-orbital”, which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness.

  14. High-throughput phenotyping and genomic selection: the frontiers of crop breeding converge.

    Science.gov (United States)

    Cabrera-Bosquet, Llorenç; Crossa, José; von Zitzewitz, Jarislav; Serret, María Dolors; Araus, José Luis

    2012-05-01

    Genomic selection (GS) and high-throughput phenotyping have recently been captivating the interest of the crop breeding community from both the public and private sectors world-wide. Both approaches promise to revolutionize the prediction of complex traits, including growth, yield and adaptation to stress. Whereas high-throughput phenotyping may help to improve understanding of crop physiology, most powerful techniques for high-throughput field phenotyping are empirical rather than analytical and comparable to genomic selection. Despite the fact that the two methodological approaches represent the extremes of what is understood as the breeding process (phenotype versus genome), they both consider the targeted traits (e.g. grain yield, growth, phenology, plant adaptation to stress) as a black box instead of dissecting them as a set of secondary traits (i.e. physiological) putatively related to the target trait. Both GS and high-throughput phenotyping have in common their empirical approach enabling breeders to use genome profile or phenotype without understanding the underlying biology. This short review discusses the main aspects of both approaches and focuses on the case of genomic selection of maize flowering traits and near-infrared spectroscopy (NIRS) and plant spectral reflectance as high-throughput field phenotyping methods for complex traits such as crop growth and yield. © 2012 Institute of Botany, Chinese Academy of Sciences.

  15. A Self-Reporting Photocatalyst for Online Fluorescence Monitoring of High Throughput RAFT Polymerization.

    Science.gov (United States)

    Yeow, Jonathan; Joshi, Sanket; Chapman, Robert; Boyer, Cyrille Andre Jean Marie

    2018-04-25

    Translating controlled/living radical polymerization (CLRP) from batch to the high throughput production of polymer libraries presents several challenges in terms of both polymer synthesis and characterization. Although recently there have been significant advances in the field of low volume, high throughput CLRP, techniques able to simultaneously monitor multiple polymerizations in an "online" manner have not yet been developed. Here, we report our discovery that 5,10,15,20-tetraphenyl-21H,23H-porphine zinc (ZnTPP) is a self-reporting photocatalyst that can mediate PET-RAFT polymerization as well as report on monomer conversion via changes in its fluorescence properties. This enables the use of a microplate reader to conduct high throughput "online" monitoring of PET-RAFT polymerizations performed directly in 384-well, low volume microtiter plates. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Chemistry

    International Nuclear Information System (INIS)

    Ferris, L.M.

    1975-01-01

    The chemical research and development efforts related to the design and ultimate operation of molten-salt breeder reactor systems are concentrated on fuel- and coolant-salt chemistry, including the development of analytical methods for use in these systems. The chemistry of tellurium in fuel salt is being studied to help elucidate the role of this element in the intergranular cracking of Hastelloy N. Studies were continued of the effect of oxygen-containing species on the equilibrium between dissolved UF 3 and dissolved UF 4 , and, in some cases, between the dissolved uranium fluorides and graphite, and the UC 2 . Several aspects of coolant-salt chemistry are under investigation. Hydroxy and oxy compounds that could be formed in molten NaBF 4 are being synthesized and characterized. Studies of the chemistry of chromium (III) compounds in fluoroborate melts were continued as part of a systematic investigation of the corrosion of structural alloys by coolant salt. An in-line voltammetric method for determining U 4+ /U 3+ ratios in fuel salt was tested in a forced-convection loop over a six-month period. (LK)

  17. Filtering high-throughput protein-protein interaction data using a combination of genomic features

    Directory of Open Access Journals (Sweden)

    Patil Ashwini

    2005-04-01

    Full Text Available Abstract Background Protein-protein interaction data used in the creation or prediction of molecular networks is usually obtained from large scale or high-throughput experiments. This experimental data is liable to contain a large number of spurious interactions. Hence, there is a need to validate the interactions and filter out the incorrect data before using them in prediction studies. Results In this study, we use a combination of 3 genomic features – structurally known interacting Pfam domains, Gene Ontology annotations and sequence homology – as a means to assign reliability to the protein-protein interactions in Saccharomyces cerevisiae determined by high-throughput experiments. Using Bayesian network approaches, we show that protein-protein interactions from high-throughput data supported by one or more genomic features have a higher likelihood ratio and hence are more likely to be real interactions. Our method has a high sensitivity (90% and good specificity (63%. We show that 56% of the interactions from high-throughput experiments in Saccharomyces cerevisiae have high reliability. We use the method to estimate the number of true interactions in the high-throughput protein-protein interaction data sets in Caenorhabditis elegans, Drosophila melanogaster and Homo sapiens to be 27%, 18% and 68% respectively. Our results are available for searching and downloading at http://helix.protein.osaka-u.ac.jp/htp/. Conclusion A combination of genomic features that include sequence, structure and annotation information is a good predictor of true interactions in large and noisy high-throughput data sets. The method has a very high sensitivity and good specificity and can be used to assign a likelihood ratio, corresponding to the reliability, to each interaction.

  18. Proceedings of the meeting on tunneling reaction and low temperature chemistry, 97 October. Tunneling reaction and quantum medium

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Tetsuo; Aratono, Yasuyuki; Ichikawa, Tsuneki; Shiotani, Masaru [eds.

    1998-02-01

    Present report is the proceedings of the 3rd Meeting on Tunneling Reaction and Low Temperature Chemistry held in Oct. 13 and 14, 1997. The main subject of the meeting is `Tunneling Reaction and Quantum Medium`. In the meeting, the physical and chemical phenomena in the liquid helium such as quantum nucleation, spectroscopy of atoms and molecules, and tunneling abstraction reaction of tritium atom were discussed as the main topics as well as the tunneling reactions in the solid hydrogen and organic compounds. Through the meetings held in 1995, 1996, and 1997, the tunneling phenomena proceeding at various temperatures (room temperature to mK) in the wide fields of chemistry, biology, and physics were discussed intensively and the importance of the tunneling phenomena in the science has been getting clear. The 12 of the presented papers are indexed individually. (J.P.N.)

  19. A Component Approach to Collaborative Scientific Software Development: Tools and Techniques Utilized by the Quantum Chemistry Science Application Partnership

    Directory of Open Access Journals (Sweden)

    Joseph P. Kenny

    2008-01-01

    Full Text Available Cutting-edge scientific computing software is complex, increasingly involving the coupling of multiple packages to combine advanced algorithms or simulations at multiple physical scales. Component-based software engineering (CBSE has been advanced as a technique for managing this complexity, and complex component applications have been created in the quantum chemistry domain, as well as several other simulation areas, using the component model advocated by the Common Component Architecture (CCA Forum. While programming models do indeed enable sound software engineering practices, the selection of programming model is just one building block in a comprehensive approach to large-scale collaborative development which must also address interface and data standardization, and language and package interoperability. We provide an overview of the development approach utilized within the Quantum Chemistry Science Application Partnership, identifying design challenges, describing the techniques which we have adopted to address these challenges and highlighting the advantages which the CCA approach offers for collaborative development.

  20. Proceedings of the meeting on tunneling reaction and low temperature chemistry, 97 October. Tunneling reaction and quantum medium

    International Nuclear Information System (INIS)

    Miyazaki, Tetsuo; Aratono, Yasuyuki; Ichikawa, Tsuneki; Shiotani, Masaru

    1998-02-01

    Present report is the proceedings of the 3rd Meeting on Tunneling Reaction and Low Temperature Chemistry held in Oct. 13 and 14, 1997. The main subject of the meeting is 'Tunneling Reaction and Quantum Medium'. In the meeting, the physical and chemical phenomena in the liquid helium such as quantum nucleation, spectroscopy of atoms and molecules, and tunneling abstraction reaction of tritium atom were discussed as the main topics as well as the tunneling reactions in the solid hydrogen and organic compounds. Through the meetings held in 1995, 1996, and 1997, the tunneling phenomena proceeding at various temperatures (room temperature to mK) in the wide fields of chemistry, biology, and physics were discussed intensively and the importance of the tunneling phenomena in the science has been getting clear. The 12 of the presented papers are indexed individually. (J.P.N.)

  1. High-throughput screening of carbohydrate-degrading enzymes using novel insoluble chromogenic substrate assay kits

    DEFF Research Database (Denmark)

    Schückel, Julia; Kracun, Stjepan Kresimir; Willats, William George Tycho

    2016-01-01

    for this is that advances in genome and transcriptome sequencing, together with associated bioinformatics tools allow for rapid identification of candidate CAZymes, but technology for determining an enzyme's biochemical characteristics has advanced more slowly. To address this technology gap, a novel high-throughput assay...... CPH and ICB substrates are provided in a 96-well high-throughput assay system. The CPH substrates can be made in four different colors, enabling them to be mixed together and thus increasing assay throughput. The protocol describes a 96-well plate assay and illustrates how this assay can be used...... for screening the activities of enzymes, enzyme cocktails, and broths....

  2. Machine learning in computational biology to accelerate high-throughput protein expression

    DEFF Research Database (Denmark)

    Sastry, Anand; Monk, Jonathan M.; Tegel, Hanna

    2017-01-01

    and machine learning identifies protein properties that hinder the HPA high-throughput antibody production pipeline. We predict protein expression and solubility with accuracies of 70% and 80%, respectively, based on a subset of key properties (aromaticity, hydropathy and isoelectric point). We guide...... the selection of protein fragments based on these characteristics to optimize high-throughput experimentation. Availability and implementation: We present the machine learning workflow as a series of IPython notebooks hosted on GitHub (https://github.com/SBRG/Protein_ML). The workflow can be used as a template...

  3. Recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Ørntoft, Torben Falck

    2007-01-01

    individually contributed to the management of the disease. However, the development of high-throughput techniques for simultaneous assessment of a large number of markers has allowed classification of tumors into clinically relevant molecular subgroups beyond those possible by pathological classification. Here......Bladder cancer is the fifth most common neoplasm in industrialized countries. Due to frequent recurrences of the superficial form of this disease, bladder cancer ranks as one of the most common cancers. Despite the description of a large number of tumor markers for bladder cancers, none have......, we review the recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers....

  4. Integrated Automation of High-Throughput Screening and Reverse Phase Protein Array Sample Preparation

    DEFF Research Database (Denmark)

    Pedersen, Marlene Lemvig; Block, Ines; List, Markus

    into automated robotic high-throughput screens, which allows subsequent protein quantification. In this integrated solution, samples are directly forwarded to automated cell lysate preparation and preparation of dilution series, including reformatting to a protein spotter-compatible format after the high......-throughput screening. Tracking of huge sample numbers and data analysis from a high-content screen to RPPAs is accomplished via MIRACLE, a custom made software suite developed by us. To this end, we demonstrate that the RPPAs generated in this manner deliver reliable protein readouts and that GAPDH and TFR levels can...

  5. High-Throughput Non-destructive Phenotyping of Traits that Contribute to Salinity Tolerance in Arabidopsis thaliana

    KAUST Repository

    Awlia, Mariam

    2016-09-28

    Reproducible and efficient high-throughput phenotyping approaches, combined with advances in genome sequencing, are facilitating the discovery of genes affecting plant performance. Salinity tolerance is a desirable trait that can be achieved through breeding, where most have aimed at selecting for plants that perform effective ion exclusion from the shoots. To determine overall plant performance under salt stress, it is helpful to investigate several plant traits collectively in one experimental setup. Hence, we developed a quantitative phenotyping protocol using a high-throughput phenotyping system, with RGB and chlorophyll fluorescence (ChlF) imaging, which captures the growth, morphology, color and photosynthetic performance of Arabidopsis thaliana plants in response to salt stress. We optimized our salt treatment by controlling the soil-water content prior to introducing salt stress. We investigated these traits over time in two accessions in soil at 150, 100, or 50 mM NaCl to find that the plants subjected to 100 mM NaCl showed the most prominent responses in the absence of symptoms of severe stress. In these plants, salt stress induced significant changes in rosette area and morphology, but less prominent changes in rosette coloring and photosystem II efficiency. Clustering of ChlF traits with plant growth of nine accessions maintained at 100 mM NaCl revealed that in the early stage of salt stress, salinity tolerance correlated with non-photochemical quenching processes and during the later stage, plant performance correlated with quantum yield. This integrative approach allows the simultaneous analysis of several phenotypic traits. In combination with various genetic resources, the phenotyping protocol described here is expected to increase our understanding of plant performance and stress responses, ultimately identifying genes that improve plant performance in salt stress conditions.

  6. Development of tight-binding, chemical-reaction-dynamics simulator for combinatorial computational chemistry

    International Nuclear Information System (INIS)

    Kubo, Momoji; Ando, Minako; Sakahara, Satoshi; Jung, Changho; Seki, Kotaro; Kusagaya, Tomonori; Endou, Akira; Takami, Seiichi; Imamura, Akira; Miyamoto, Akira

    2004-01-01

    Recently, we have proposed a new concept called 'combinatorial computational chemistry' to realize a theoretical, high-throughput screening of catalysts and materials. We have already applied our combinatorial, computational-chemistry approach, mainly based on static first-principles calculations, to various catalysts and materials systems and its applicability to the catalysts and materials design was strongly confirmed. In order to realize more effective and efficient combinatorial, computational-chemistry screening, a high-speed, chemical-reaction-dynamics simulator based on quantum-chemical, molecular-dynamics method is essential. However, to the best of our knowledge, there is no chemical-reaction-dynamics simulator, which has an enough high-speed ability to perform a high-throughput screening. In the present study, we have succeeded in the development of a chemical-reaction-dynamics simulator based on our original, tight-binding, quantum-chemical, molecular-dynamics method, which is more than 5000 times faster than the regular first-principles, molecular-dynamics method. Moreover, its applicability and effectiveness to the atomistic clarification of the methanol-synthesis dynamics at reaction temperature were demonstrated

  7. Quantum confinement and surface chemistry of 0.8–1.6 nm hydrosilylated silicon nanocrystals

    International Nuclear Information System (INIS)

    Pi Xiao-Dong; Wang Rong; Yang De-Ren

    2014-01-01

    In the framework of density functional theory (DFT), we have studied the electronic properties of alkene/alkyne-hydrosilylated silicon nanocrystals (Si NCs) in the size range from 0.8 nm to 1.6 nm. Among the alkenes with all kinds of functional groups considered in this work, only those containing —NH 2 and —C 4 H 3 S lead to significant hydrosilylation-induced changes in the gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of an Si NC at the ground state. The quantum confinement effect is dominant for all of the alkene-hydrosilylated Si NCs at the ground state. At the excited state, the prevailing effect of surface chemistry only occurs at the smallest (0.8 nm) Si NCs hydrosilylated with alkenes containing —NH 2 and —C 4 H 3 S. Although the alkyne hydrosilylation gives rise to a more significant surface chemistry effect than alkene hydrosilylation, the quantum confinement effect remains dominant for alkyne-hydrosilylated Si NCs at the ground state. However, at the excited state, the effect of surface chemistry induced by the hydrosilylation with conjugated alkynes is strong enough to prevail over that of quantum confinement. (condensed matter: structural, mechanical, and thermal properties)

  8. Performance Optimization of Tensor Contraction Expressions for Many Body Methods in Quantum Chemistry

    International Nuclear Information System (INIS)

    Hartono, Albert; Lu, Qingda; Henretty, Thomas; Krishnamoorthy, Sriram; Zhang, Huaijian; Baumgartner, Gerald; Bernholdt, David E.; Nooijen, Marcel; Pitzer, Russell M.; Ramanujam, J.; Sadayappan, Ponnuswamy

    2009-01-01

    Complex tensor contraction expressions arise in accurate electronic structure models in quantum chemistry, such as the coupled cluster method. This paper addresses two complementary aspects of performance optimization of such tensor contraction expressions. Transformations using algebraic properties of commutativity and associativity can be used to significantly decrease the number of arithmetic operations required for evaluation of these expressions. The identification of common subexpressions among a set of tensor contraction expressions can result in a reduction of the total number of operations required to evaluate the tensor contractions. The first part of the paper describes an effective algorithm for operation minimization with common subexpression identification and demonstrates its effectiveness on tensor contraction expressions for coupled cluster equations. The second part of the paper highlights the importance of data layout transformation in the optimization of tensor contraction computations on modern processors. A number of considerations such as minimization of cache misses and utilization of multimedia vector instructions are discussed. A library for efficient index permutation of multi-dimensional tensors is described and experimental performance data is provided that demonstrates its effectiveness.

  9. Performance Optimization of Tensor Contraction Expressions for Many Body Methods in Quantum Chemistry

    International Nuclear Information System (INIS)

    Krishnamoorthy, Sriram; Bernholdt, David E.; Pitzer, R.M.; Sadayappan, Ponnuswamy

    2009-01-01

    Complex tensor contraction expressions arise in accurate electronic structure models in quantum chemistry, such as the coupled cluster method. This paper addresses two complementary aspects of performance optimization of such tensor contraction expressions. Transformations using algebraic properties of commutativity and associativity can be used to significantly decrease the number of arithmetic operations required for evaluation of these expressions. The identification of common subexpressions among a set of tensor contraction expressions can result in a reduction of the total number of operations required to evaluate the tensor contractions. The first part of the paper describes an effective algorithm for operation minimization with common subexpression identification and demonstrates its effectiveness on tensor contraction expressions for coupled cluster equations. The second part of the paper highlights the importance of data layout transformation in the optimization of tensor contraction computations on modern processors. A number of considerations, such as minimization of cache misses and utilization of multimedia vector instructions, are discussed. A library for efficient index permutation of multidimensional tensors is described, and experimental performance data is provided that demonstrates its effectiveness.

  10. Time-dependent quantum chemistry of laser driven many-electron molecules

    International Nuclear Information System (INIS)

    Nguyen-Dang, Thanh-Tung; Couture-Bienvenue, Étienne; Viau-Trudel, Jérémy; Sainjon, Amaury

    2014-01-01

    A Time-Dependent Configuration Interaction approach using multiple Feshbach partitionings, corresponding to multiple ionization stages of a laser-driven molecule, has recently been proposed [T.-T. Nguyen-Dang and J. Viau-Trudel, J. Chem. Phys. 139, 244102 (2013)]. To complete this development toward a fully ab-initio method for the calculation of time-dependent electronic wavefunctions of an N-electron molecule, we describe how tools of multiconfiguration quantum chemistry such as the management of the configuration expansion space using Graphical Unitary Group Approach concepts can be profitably adapted to the new context, that of time-resolved electronic dynamics, as opposed to stationary electronic structure. The method is applied to calculate the detailed, sub-cycle electronic dynamics of BeH 2 , treated in a 3–21G bound-orbital basis augmented by a set of orthogonalized plane-waves representing continuum-type orbitals, including its ionization under an intense λ = 800 nm or λ = 80 nm continuous-wave laser field. The dynamics is strongly non-linear at the field-intensity considered (I ≃ 10 15 W/cm 2 ), featuring important ionization of an inner-shell electron and strong post-ionization bound-electron dynamics

  11. Advances in molecular quantum chemistry contained in the Q-Chem 4 program package

    Science.gov (United States)

    Shao, Yihan; Gan, Zhengting; Epifanovsky, Evgeny; Gilbert, Andrew T. B.; Wormit, Michael; Kussmann, Joerg; Lange, Adrian W.; Behn, Andrew; Deng, Jia; Feng, Xintian; Ghosh, Debashree; Goldey, Matthew; Horn, Paul R.; Jacobson, Leif D.; Kaliman, Ilya; Khaliullin, Rustam Z.; Kuś, Tomasz; Landau, Arie; Liu, Jie; Proynov, Emil I.; Rhee, Young Min; Richard, Ryan M.; Rohrdanz, Mary A.; Steele, Ryan P.; Sundstrom, Eric J.; Woodcock, H. Lee, III; Zimmerman, Paul M.; Zuev, Dmitry; Albrecht, Ben; Alguire, Ethan; Austin, Brian; Beran, Gregory J. O.; Bernard, Yves A.; Berquist, Eric; Brandhorst, Kai; Bravaya, Ksenia B.; Brown, Shawn T.; Casanova, David; Chang, Chun-Min; Chen, Yunqing; Chien, Siu Hung; Closser, Kristina D.; Crittenden, Deborah L.; Diedenhofen, Michael; DiStasio, Robert A., Jr.; Do, Hainam; Dutoi, Anthony D.; Edgar, Richard G.; Fatehi, Shervin; Fusti-Molnar, Laszlo; Ghysels, An; Golubeva-Zadorozhnaya, Anna; Gomes, Joseph; Hanson-Heine, Magnus W. D.; Harbach, Philipp H. P.; Hauser, Andreas W.; Hohenstein, Edward G.; Holden, Zachary C.; Jagau, Thomas-C.; Ji, Hyunjun; Kaduk, Benjamin; Khistyaev, Kirill; Kim, Jaehoon; Kim, Jihan; King, Rollin A.; Klunzinger, Phil; Kosenkov, Dmytro; Kowalczyk, Tim; Krauter, Caroline M.; Lao, Ka Un; Laurent, Adèle D.; Lawler, Keith V.; Levchenko, Sergey V.; Lin, Ching Yeh; Liu, Fenglai; Livshits, Ester; Lochan, Rohini C.; Luenser, Arne; Manohar, Prashant; Manzer, Samuel F.; Mao, Shan-Ping; Mardirossian, Narbe; Marenich, Aleksandr V.; Maurer, Simon A.; Mayhall, Nicholas J.; Neuscamman, Eric; Oana, C. Melania; Olivares-Amaya, Roberto; O'Neill, Darragh P.; Parkhill, John A.; Perrine, Trilisa M.; Peverati, Roberto; Prociuk, Alexander; Rehn, Dirk R.; Rosta, Edina; Russ, Nicholas J.; Sharada, Shaama M.; Sharma, Sandeep; Small, David W.; Sodt, Alexander; Stein, Tamar; Stück, David; Su, Yu-Chuan; Thom, Alex J. W.; Tsuchimochi, Takashi; Vanovschi, Vitalii; Vogt, Leslie; Vydrov, Oleg; Wang, Tao; Watson, Mark A.; Wenzel, Jan; White, Alec; Williams, Christopher F.; Yang, Jun; Yeganeh, Sina; Yost, Shane R.; You, Zhi-Qiang; Zhang, Igor Ying; Zhang, Xing; Zhao, Yan; Brooks, Bernard R.; Chan, Garnet K. L.; Chipman, Daniel M.; Cramer, Christopher J.; Goddard, William A., III; Gordon, Mark S.; Hehre, Warren J.; Klamt, Andreas; Schaefer, Henry F., III; Schmidt, Michael W.; Sherrill, C. David; Truhlar, Donald G.; Warshel, Arieh; Xu, Xin; Aspuru-Guzik, Alán; Baer, Roi; Bell, Alexis T.; Besley, Nicholas A.; Chai, Jeng-Da; Dreuw, Andreas; Dunietz, Barry D.; Furlani, Thomas R.; Gwaltney, Steven R.; Hsu, Chao-Ping; Jung, Yousung; Kong, Jing; Lambrecht, Daniel S.; Liang, WanZhen; Ochsenfeld, Christian; Rassolov, Vitaly A.; Slipchenko, Lyudmila V.; Subotnik, Joseph E.; Van Voorhis, Troy; Herbert, John M.; Krylov, Anna I.; Gill, Peter M. W.; Head-Gordon, Martin

    2015-01-01

    A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller-Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.

  12. Using machine learning and quantum chemistry descriptors to predict the toxicity of ionic liquids.

    Science.gov (United States)

    Cao, Lingdi; Zhu, Peng; Zhao, Yongsheng; Zhao, Jihong

    2018-06-15

    Large-scale application of ionic liquids (ILs) hinges on the advancement of designable and eco-friendly nature. Research of the potential toxicity of ILs towards different organisms and trophic levels is insufficient. Quantitative structure-activity relationships (QSAR) model is applied to evaluate the toxicity of ILs towards the leukemia rat cell line (ICP-81). The structures of 57 cations and 21 anions were optimized by quantum chemistry. The electrostatic potential surface area (S EP ) and charge distribution area (S σ-profile ) descriptors are calculated and used to predict the toxicity of ILs. The performance and predictive aptitude of extreme learning machine (ELM) model are analyzed and compared with those of multiple linear regression (MLR) and support vector machine (SVM) models. The highest R 2 and the lowest AARD% and RMSE of the training set, test set and total set for the ELM are observed, which validates the superior performance of the ELM than that of obtained by the MLR and SVM. The applicability domain of the model is assessed by the Williams plot. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. A photoelectron imaging and quantum chemistry study of the deprotonated indole anion.

    Science.gov (United States)

    Parkes, Michael A; Crellin, Jonathan; Henley, Alice; Fielding, Helen H

    2018-05-29

    Indole is an important molecular motif in many biological molecules and exists in its deprotonated anionic form in the cyan fluorescent protein, an analogue of green fluorescent protein. However, the electronic structure of the deprotonated indole anion has been relatively unexplored. Here, we use a combination of anion photoelectron velocity-map imaging measurements and quantum chemistry calculations to probe the electronic structure of the deprotonated indole anion. We report vertical detachment energies (VDEs) of 2.45 ± 0.05 eV and 3.20 ± 0.05 eV, respectively. The value for D0 is in agreement with recent high-resolution measurements whereas the value for D1 is a new measurement. We find that the first electronically excited singlet state of the anion, S1(ππ*), lies above the VDE and has shape resonance character with respect to the D0 detachment continuum and Feshbach resonance character with respect to the D1 continuum.

  14. High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the Identification of PPIs Antagonists.

    Science.gov (United States)

    Wu, Bainan; Barile, Elisa; De, Surya K; Wei, Jun; Purves, Angela; Pellecchia, Maurizio

    2015-01-01

    In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications.

  15. High-throughput exploration of thermoelectric and mechanical properties of amorphous NbO{sub 2} with transition metal additions

    Energy Technology Data Exchange (ETDEWEB)

    Music, Denis, E-mail: music@mch.rwth-aachen.de; Geyer, Richard W.; Hans, Marcus [Materials Chemistry, RWTH Aachen University, Kopernikusstr. 10, 52074 Aachen (Germany)

    2016-07-28

    To increase the thermoelectric efficiency and reduce the thermal fatigue upon cyclic heat loading, alloying of amorphous NbO{sub 2} with all 3d and 5d transition metals has systematically been investigated using density functional theory. It was found that Ta fulfills the key design criteria, namely, enhancement of the Seebeck coefficient and positive Cauchy pressure (ductility gauge). These quantum mechanical predictions were validated by assessing the thermoelectric and elastic properties on combinatorial thin films, which is a high-throughput approach. The maximum power factor is 2813 μW m{sup −1} K{sup −2} for the Ta/Nb ratio of 0.25, which is a hundredfold increment compared to pure NbO{sub 2} and exceeds many oxide thermoelectrics. Based on the elasticity measurements, the consistency between theory and experiment for the Cauchy pressure was attained within 2%. On the basis of the electronic structure analysis, these configurations can be perceived as metallic, which is consistent with low electrical resistivity and ductile behavior. Furthermore, a pronounced quantum confinement effect occurs, which is identified as the physical origin for the Seebeck coefficient enhancement.

  16. High-throughput exploration of thermoelectric and mechanical properties of amorphous NbO_2 with transition metal additions

    International Nuclear Information System (INIS)

    Music, Denis; Geyer, Richard W.; Hans, Marcus

    2016-01-01

    To increase the thermoelectric efficiency and reduce the thermal fatigue upon cyclic heat loading, alloying of amorphous NbO_2 with all 3d and 5d transition metals has systematically been investigated using density functional theory. It was found that Ta fulfills the key design criteria, namely, enhancement of the Seebeck coefficient and positive Cauchy pressure (ductility gauge). These quantum mechanical predictions were validated by assessing the thermoelectric and elastic properties on combinatorial thin films, which is a high-throughput approach. The maximum power factor is 2813 μW m"−"1 K"−"2 for the Ta/Nb ratio of 0.25, which is a hundredfold increment compared to pure NbO_2 and exceeds many oxide thermoelectrics. Based on the elasticity measurements, the consistency between theory and experiment for the Cauchy pressure was attained within 2%. On the basis of the electronic structure analysis, these configurations can be perceived as metallic, which is consistent with low electrical resistivity and ductile behavior. Furthermore, a pronounced quantum confinement effect occurs, which is identified as the physical origin for the Seebeck coefficient enhancement.

  17. Solid-phase cloning for high-throughput assembly of single and multiple DNA parts

    DEFF Research Database (Denmark)

    Lundqvist, Magnus; Edfors, Fredrik; Sivertsson, Åsa

    2015-01-01

    We describe solid-phase cloning (SPC) for high-throughput assembly of expression plasmids. Our method allows PCR products to be put directly into a liquid handler for capture and purification using paramagnetic streptavidin beads and conversion into constructs by subsequent cloning reactions. We ...

  18. Quantitative in vitro-to-in vivo extrapolation in a high-throughput environment

    International Nuclear Information System (INIS)

    Wetmore, Barbara A.

    2015-01-01

    High-throughput in vitro toxicity screening provides an efficient way to identify potential biological targets for environmental and industrial chemicals while conserving limited testing resources. However, reliance on the nominal chemical concentrations in these in vitro assays as an indicator of bioactivity may misrepresent potential in vivo effects of these chemicals due to differences in clearance, protein binding, bioavailability, and other pharmacokinetic factors. Development of high-throughput in vitro hepatic clearance and protein binding assays and refinement of quantitative in vitro-to-in vivo extrapolation (QIVIVE) methods have provided key tools to predict xenobiotic steady state pharmacokinetics. Using a process known as reverse dosimetry, knowledge of the chemical steady state behavior can be incorporated with HTS data to determine the external in vivo oral exposure needed to achieve internal blood concentrations equivalent to those eliciting bioactivity in the assays. These daily oral doses, known as oral equivalents, can be compared to chronic human exposure estimates to assess whether in vitro bioactivity would be expected at the dose-equivalent level of human exposure. This review will describe the use of QIVIVE methods in a high-throughput environment and the promise they hold in shaping chemical testing priorities and, potentially, high-throughput risk assessment strategies

  19. Discovery of viruses and virus-like pathogens in pistachio using high-throughput sequencing

    Science.gov (United States)

    Pistachio (Pistacia vera L.) trees from the National Clonal Germplasm Repository (NCGR) and orchards in California were surveyed for viruses and virus-like agents by high-throughput sequencing (HTS). Analyses of 60 trees including clonal UCB-1 hybrid rootstock (P. atlantica × P. integerrima) identif...

  20. Development of scalable high throughput fermentation approaches for physiological characterisation of yeast and filamentous fungi

    DEFF Research Database (Denmark)

    Knudsen, Peter Boldsen

    producing the heterologous model polyketide, 6-methylsalicylic acid (6-MSA). An automated methodology for high throughput screening focusing on growth rates, together with a fully automated method for quantitative physiological characterisation in microtiter plates, was established for yeast. Full...

  1. High throughput deposition of hydrogenated amorphous carbon coatings on rubber with expanding thermal plasma

    NARCIS (Netherlands)

    Pei, Y.T.; Eivani, A.R.; Zaharia, T.; Kazantis, A.V.; Sanden, van de M.C.M.; De Hosson, J.T.M.

    2014-01-01

    Flexible hydrogenated amorphous carbon (a-C:H) thin film coated on rubbers has shown outstanding protection of rubber seals from friction and wear. This work concentrates on the potential advances of expanding thermal plasma (ETP) process for a high throughput deposition of a-C:H thin films in

  2. High-throughput investigation of polymerization kinetics by online monitoring of GPC and GC

    NARCIS (Netherlands)

    Hoogenboom, R.; Fijten, M.W.M.; Abeln, C.H.; Schubert, U.S.

    2004-01-01

    Gel permeation chromatography (GPC) and gas chromatography (GC) were successfully introduced into a high-throughput workflow. The feasibility and limitations of online GPC with a high-speed column was evaluated by measuring polystyrene standards and comparison of the results with regular offline GPC

  3. Insights into Sonogashira cross-coupling by high-throughput kinetics and descriptor modeling

    NARCIS (Netherlands)

    an der Heiden, M.R.; Plenio, H.; Immel, S.; Burello, E.; Rothenberg, G.; Hoefsloot, H.C.J.

    2008-01-01

    A method is presented for the high-throughput monitoring of reaction kinetics in homogeneous catalysis, running up to 25 coupling reactions in a single reaction vessel. This method is demonstrated and validated on the Sonogashira reaction, analyzing the kinetics for almost 500 coupling reactions.

  4. Modeling Disordered Materials with a High Throughput ab-initio Approach

    Science.gov (United States)

    2015-11-13

    Modeling Disordered Materials with a High Throughput ab - initio Approach Kesong Yang,1 Corey Oses,2 and Stefano Curtarolo3, 4 1Department of...J. Furthmüller, Efficient iterative schemes for ab initio total-energy calculations using a plane-wave basis set, Phys. Rev. B 54, 11169–11186 (1996

  5. High-throughput assessment of context-dependent effects of chromatin proteins

    NARCIS (Netherlands)

    Brueckner, L. (Laura); Van Arensbergen, J. (Joris); Akhtar, W. (Waseem); L. Pagie (Ludo); B. van Steensel (Bas)

    2016-01-01

    textabstractBackground: Chromatin proteins control gene activity in a concerted manner. We developed a high-throughput assay to study the effects of the local chromatin environment on the regulatory activity of a protein of interest. The assay combines a previously reported multiplexing strategy

  6. High-throughput, temperature-controlled microchannel acoustophoresis device made with rapid prototyping

    DEFF Research Database (Denmark)

    Adams, Jonathan D; Ebbesen, Christian L.; Barnkob, Rune

    2012-01-01

    -slide format using low-cost, rapid-prototyping techniques. This high-throughput acoustophoresis chip (HTAC) utilizes a temperature-stabilized, standing ultrasonic wave, which imposes differential acoustic radiation forces that can separate particles according to size, density and compressibility. The device...

  7. A high-throughput method for GMO multi-detection using a microfluidic dynamic array

    NARCIS (Netherlands)

    Brod, F.C.A.; Dijk, van J.P.; Voorhuijzen, M.M.; Dinon, A.Z.; Guimarães, L.H.S.; Scholtens, I.M.J.; Arisi, A.C.M.; Kok, E.J.

    2014-01-01

    The ever-increasing production of genetically modified crops generates a demand for high-throughput DNAbased methods for the enforcement of genetically modified organisms (GMO) labelling requirements. The application of standard real-time PCR will become increasingly costly with the growth of the

  8. Retrofit Strategies for Incorporating Xenobiotic Metabolism into High Throughput Screening Assays (EMGS)

    Science.gov (United States)

    The US EPA’s ToxCast program is designed to assess chemical perturbations of molecular and cellular endpoints using a variety of high-throughput screening (HTS) assays. However, existing HTS assays have limited or no xenobiotic metabolism which could lead to a mischaracterization...

  9. Development of automatic image analysis methods for high-throughput and high-content screening

    NARCIS (Netherlands)

    Di, Zi

    2013-01-01

    This thesis focuses on the development of image analysis methods for ultra-high content analysis of high-throughput screens where cellular phenotype responses to various genetic or chemical perturbations that are under investigation. Our primary goal is to deliver efficient and robust image analysis

  10. High-throughput verification of transcriptional starting sites by Deep-RACE

    DEFF Research Database (Denmark)

    Olivarius, Signe; Plessy, Charles; Carninci, Piero

    2009-01-01

    We present a high-throughput method for investigating the transcriptional starting sites of genes of interest, which we named Deep-RACE (Deep–rapid amplification of cDNA ends). Taking advantage of the latest sequencing technology, it allows the parallel analysis of multiple genes and is free...

  11. New approach for high-throughput screening of drug activity on Plasmodium liver stages.

    NARCIS (Netherlands)

    Gego, A.; Silvie, O.; Franetich, J.F.; Farhati, K.; Hannoun, L.; Luty, A.J.F.; Sauerwein, R.W.; Boucheix, C.; Rubinstein, E.; Mazier, D.

    2006-01-01

    Plasmodium liver stages represent potential targets for antimalarial prophylactic drugs. Nevertheless, there is a lack of molecules active on these stages. We have now developed a new approach for the high-throughput screening of drug activity on Plasmodium liver stages in vitro, based on an

  12. Detection and quantification of intracellular bacterial colonies by automated, high-throughput microscopy

    DEFF Research Database (Denmark)

    Ernstsen, Christina L; Login, Frédéric H; Jensen, Helene H

    2017-01-01

    To target bacterial pathogens that invade and proliferate inside host cells, it is necessary to design intervention strategies directed against bacterial attachment, cellular invasion and intracellular proliferation. We present an automated microscopy-based, fast, high-throughput method for analy...

  13. A high throughput DNA extraction method with high yield and quality

    Directory of Open Access Journals (Sweden)

    Xin Zhanguo

    2012-07-01

    Full Text Available Abstract Background Preparation of large quantity and high quality genomic DNA from a large number of plant samples is a major bottleneck for most genetic and genomic analyses, such as, genetic mapping, TILLING (Targeting Induced Local Lesion IN Genome, and next-generation sequencing directly from sheared genomic DNA. A variety of DNA preparation methods and commercial kits are available. However, they are either low throughput, low yield, or costly. Here, we describe a method for high throughput genomic DNA isolation from sorghum [Sorghum bicolor (L. Moench] leaves and dry seeds with high yield, high quality, and affordable cost. Results We developed a high throughput DNA isolation method by combining a high yield CTAB extraction method with an improved cleanup procedure based on MagAttract kit. The method yielded large quantity and high quality DNA from both lyophilized sorghum leaves and dry seeds. The DNA yield was improved by nearly 30 fold with 4 times less consumption of MagAttract beads. The method can also be used in other plant species, including cotton leaves and pine needles. Conclusion A high throughput system for DNA extraction from sorghum leaves and seeds was developed and validated. The main advantages of the method are low cost, high yield, high quality, and high throughput. One person can process two 96-well plates in a working day at a cost of $0.10 per sample of magnetic beads plus other consumables that other methods will also need.

  14. High-throughput transformation of Saccharomyces cerevisiae using liquid handling robots.

    Directory of Open Access Journals (Sweden)

    Guangbo Liu

    Full Text Available Saccharomyces cerevisiae (budding yeast is a powerful eukaryotic model organism ideally suited to high-throughput genetic analyses, which time and again has yielded insights that further our understanding of cell biology processes conserved in humans. Lithium Acetate (LiAc transformation of yeast with DNA for the purposes of exogenous protein expression (e.g., plasmids or genome mutation (e.g., gene mutation, deletion, epitope tagging is a useful and long established method. However, a reliable and optimized high throughput transformation protocol that runs almost no risk of human error has not been described in the literature. Here, we describe such a method that is broadly transferable to most liquid handling high-throughput robotic platforms, which are now commonplace in academic and industry settings. Using our optimized method, we are able to comfortably transform approximately 1200 individual strains per day, allowing complete transformation of typical genomic yeast libraries within 6 days. In addition, use of our protocol for gene knockout purposes also provides a potentially quicker, easier and more cost-effective approach to generating collections of double mutants than the popular and elegant synthetic genetic array methodology. In summary, our methodology will be of significant use to anyone interested in high throughput molecular and/or genetic analysis of yeast.

  15. High throughput "omics" approaches to assess the effects of phytochemicals in human health studies

    Czech Academy of Sciences Publication Activity Database

    Ovesná, J.; Slabý, O.; Toussaint, O.; Kodíček, M.; Maršík, Petr; Pouchová, V.; Vaněk, Tomáš

    2008-01-01

    Roč. 99, E-S1 (2008), ES127-ES134 ISSN 0007-1145 R&D Projects: GA MŠk(CZ) 1P05OC054 Institutional research plan: CEZ:AV0Z50380511 Keywords : Nutrigenomics * Phytochemicals * High throughput platforms Subject RIV: GM - Food Processing Impact factor: 2.764, year: 2008

  16. High-Throughput Dietary Exposure Predictions for Chemical Migrants from Food Packaging Materials

    Science.gov (United States)

    United States Environmental Protection Agency researchers have developed a Stochastic Human Exposure and Dose Simulation High -Throughput (SHEDS-HT) model for use in prioritization of chemicals under the ExpoCast program. In this research, new methods were implemented in SHEDS-HT...

  17. ToxCast Workflow: High-throughput screening assay data processing, analysis and management (SOT)

    Science.gov (United States)

    US EPA’s ToxCast program is generating data in high-throughput screening (HTS) and high-content screening (HCS) assays for thousands of environmental chemicals, for use in developing predictive toxicity models. Currently the ToxCast screening program includes over 1800 unique c...

  18. High-throughput sequencing of forensic genetic samples using punches of FTA cards with buccal swabs

    DEFF Research Database (Denmark)

    Kampmann, Marie-Louise; Buchard, Anders; Børsting, Claus

    2016-01-01

    Here, we demonstrate that punches from buccal swab samples preserved on FTA cards can be used for high-throughput DNA sequencing, also known as massively parallel sequencing (MPS). We typed 44 reference samples with the HID-Ion AmpliSeq Identity Panel using washed 1.2 mm punches from FTA cards...

  19. 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...

  20. 40 CFR Table 3 to Subpart Eeee of... - Operating Limits-High Throughput Transfer Racks

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Operating Limits-High Throughput Transfer Racks 3 Table 3 to Subpart EEEE of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION... Throughput Transfer Racks As stated in § 63.2346(e), you must comply with the operating limits for existing...

  1. High-throughput testing of terpenoid biosynthesis candidate genes using transient expression in Nicotiana benthamiana

    DEFF Research Database (Denmark)

    Bach, Søren Spanner; Bassard, Jean-Étienne André; Andersen-Ranberg, Johan

    2014-01-01

    To respond to the rapidly growing number of genes putatively involved in terpenoid metabolism, a robust high-throughput platform for functional testing is needed. An in planta expression system offers several advantages such as the capacity to produce correctly folded and active enzymes localized...

  2. High-throughput computational methods and software for quantitative trait locus (QTL) mapping

    NARCIS (Netherlands)

    Arends, Danny

    2014-01-01

    De afgelopen jaren zijn vele nieuwe technologieen zoals Tiling arrays en High throughput DNA sequencing een belangrijke rol gaan spelen binnen het onderzoeksveld van de systeem genetica. Voor onderzoekers is het extreem belangrijk om te begrijpen dat deze methodes hun manier van werken zullen gaan

  3. Evaluation of Simple and Inexpensive High-Throughput Methods for Phytic Acid Determination

    DEFF Research Database (Denmark)

    Raboy, Victor; Johnson, Amy; Bilyeu, Kristin

    2017-01-01

    High-throughput/low-cost/low-tech methods for phytic acid determination that are sufficiently accurate and reproducible would be of value in plant genetics, crop breeding and in the food and feed industries. Variants of two candidate methods, those described by Vaintraub and Lapteva (Anal Biochem...... and legume flours regardless of endogenous phytic acid levels or matrix constituents....

  4. High-throughput open source computational methods for genetics and genomics

    NARCIS (Netherlands)

    Prins, J.C.P.

    2015-01-01

    Biology is increasingly data driven by virtue of the development of high-throughput technologies, such as DNA and RNA sequencing. Computational biology and bioinformatics are scientific disciplines that cross-over between the disciplines of biology, informatics and statistics; which is clearly

  5. The protein crystallography beamline BW6 at DORIS - automatic operation and high-throughput data collection

    CERN Document Server

    Blume, H; Bourenkov, G P; Kosciesza, D; Bartunik, H D

    2001-01-01

    The wiggler beamline BW6 at DORIS has been optimized for de-novo solution of protein structures on the basis of MAD phasing. Facilities for automatic data collection, rapid data transfer and storage, and online processing have been developed which provide adequate conditions for high-throughput applications, e.g., in structural genomics.

  6. tcpl: The ToxCast Pipeline for High-Throughput Screening Data

    Science.gov (United States)

    Motivation: The large and diverse high-throughput chemical screening efforts carried out by the US EPAToxCast program requires an efficient, transparent, and reproducible data pipeline.Summary: The tcpl R package and its associated MySQL database provide a generalized platform fo...

  7. Reverse Phase Protein Arrays for High-Throughput Protein Measurements in Mammospheres

    DEFF Research Database (Denmark)

    Pedersen, Marlene Lemvig; Block, Ines; List, Markus

    Protein Array (RPPA)-based readout format integrated into robotic siRNA screening. This technique would allow post-screening high-throughput quantification of protein changes. Recently, breast cancer stem cells (BCSCs) have attracted much attention, as a tumor- and metastasis-driving subpopulation...

  8. High throughput generated micro-aggregates of chondrocytes stimulate cartilage formation in vitro and in vivo

    NARCIS (Netherlands)

    Moreira Teixeira, Liliana; Leijten, Jeroen Christianus Hermanus; Sobral, J.; Jin, R.; van Apeldoorn, Aart A.; Feijen, Jan; van Blitterswijk, Clemens; Dijkstra, Pieter J.; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Cell-based cartilage repair strategies such as matrix-induced autologous chondrocyte implantation (MACI) could be improved by enhancing cell performance. We hypothesised that micro-aggregates of chondrocytes generated in high-throughput prior to implantation in a defect could stimulate cartilaginous

  9. Chemistry

    International Nuclear Information System (INIS)

    Ferris, L.M.

    1976-01-01

    Research progress is reported in programs on fuel-salt chemistry, properties of compounds in the Li--Te system, Te spectroscopy UF 4 --H equilibria, porous electrode studies of molten salts, fuel salt-coolant salt reactions, thermodynamic properties of transition-metal fluorides, and properties of sodium fluoroborate. Developmental work on analytical methods is summarized including in-line analysis of molten MSBR fuel, analysis of coolant-salts for tritium, analysis of molten LiF--BeF 2 --ThF 4 for Fe and analysis of LiF--BeF--ThF 4 for Te

  10. High-Throughput Tabular Data Processor - Platform independent graphical tool for processing large data sets.

    Science.gov (United States)

    Madanecki, Piotr; Bałut, Magdalena; Buckley, Patrick G; Ochocka, J Renata; Bartoszewski, Rafał; Crossman, David K; Messiaen, Ludwine M; Piotrowski, Arkadiusz

    2018-01-01

    High-throughput technologies generate considerable amount of data which often requires bioinformatic expertise to analyze. Here we present High-Throughput Tabular Data Processor (HTDP), a platform independent Java program. HTDP works on any character-delimited column data (e.g. BED, GFF, GTF, PSL, WIG, VCF) from multiple text files and supports merging, filtering and converting of data that is produced in the course of high-throughput experiments. HTDP can also utilize itemized sets of conditions from external files for complex or repetitive filtering/merging tasks. The program is intended to aid global, real-time processing of large data sets using a graphical user interface (GUI). Therefore, no prior expertise in programming, regular expression, or command line usage is required of the user. Additionally, no a priori assumptions are imposed on the internal file composition. We demonstrate the flexibility and potential of HTDP in real-life research tasks including microarray and massively parallel sequencing, i.e. identification of disease predisposing variants in the next generation sequencing data as well as comprehensive concurrent analysis of microarray and sequencing results. We also show the utility of HTDP in technical tasks including data merge, reduction and filtering with external criteria files. HTDP was developed to address functionality that is missing or rudimentary in other GUI software for processing character-delimited column data from high-throughput technologies. Flexibility, in terms of input file handling, provides long term potential functionality in high-throughput analysis pipelines, as the program is not limited by the currently existing applications and data formats. HTDP is available as the Open Source software (https://github.com/pmadanecki/htdp).

  11. Secondary Structures in Phe-Containing Isolated Dipeptide Chains: Laser Spectroscopy vs Quantum Chemistry.

    Science.gov (United States)

    Loquais, Yohan; Gloaguen, Eric; Habka, Sana; Vaquero-Vara, Vanesa; Brenner, Valérie; Tardivel, Benjamin; Mons, Michel

    2015-06-11

    The intrinsic conformational landscape of two phenylalanine-containing protein chain models (-Gly-Phe- and -Ala-Phe- sequences) has been investigated theoretically and experimentally in the gas phase. The near UV spectroscopy (first ππ* transition of the Phe ring) is obtained experimentally under jet conditions where the conformational features can be resolved. Single-conformation IR spectroscopy in the NH stretch region is then obtained by IR/UV double resonance in the ground state, leading to resolved vibrational spectra that are assigned in terms of conformation and H-bonding content from comparison with quantum chemistry calculations. For the main conformer, whose UV spectrum exhibits a significant Franck-Condon activity in low frequency modes involving peptide backbone motions relative to the Phe chromophore, excited state IR spectroscopy has also been recorded in a UV/IR/UV experiment. The NH stretch spectral changes observed in such a ππ* labeling experiment enable us to determine those NH bonds that are coupled to the phenyl ring; they are compared to CC2 excited state calculations to quantify the geometry change upon ππ* excitation. The complete and consistent series of data obtained enable us to propose an unambiguous assignment for the gallery of conformers observed and to demonstrate that, in these two sequences, three conceptually important local structural motifs of proteins (β-strands, 27 ribbons, and β-turns) are represented. The satisfactory agreement between the experimental conformational distribution and the predicted landscape anticipated from the DFT-D approach demonstrates the capabilities of a theoretical method that accounts for dispersive interactions. It also shows that the flaws, inherent to a resonant two-photon ionization detection scheme, often evoked for aromatic chromophores, do not seem to be significant in the case of Phe.

  12. 40 CFR Table 9 to Subpart Eeee of... - Continuous Compliance With Operating Limits-High Throughput Transfer Racks

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Continuous Compliance With Operating Limits-High Throughput Transfer Racks 9 Table 9 to Subpart EEEE of Part 63 Protection of Environment...—Continuous Compliance With Operating Limits—High Throughput Transfer Racks As stated in §§ 63.2378(a) and (b...

  13. High-throughput characterization of film thickness in thin film materials libraries by digital holographic microscopy

    International Nuclear Information System (INIS)

    Lai Yiuwai; Hofmann, Martin R; Ludwig, Alfred; Krause, Michael; Savan, Alan; Thienhaus, Sigurd; Koukourakis, Nektarios

    2011-01-01

    A high-throughput characterization technique based on digital holography for mapping film thickness in thin-film materials libraries was developed. Digital holographic microscopy is used for fully automatic measurements of the thickness of patterned films with nanometer resolution. The method has several significant advantages over conventional stylus profilometry: it is contactless and fast, substrate bending is compensated, and the experimental setup is simple. Patterned films prepared by different combinatorial thin-film approaches were characterized to investigate and demonstrate this method. The results show that this technique is valuable for the quick, reliable and high-throughput determination of the film thickness distribution in combinatorial materials research. Importantly, it can also be applied to thin films that have been structured by shadow masking.

  14. High-throughput characterization of film thickness in thin film materials libraries by digital holographic microscopy.

    Science.gov (United States)

    Lai, Yiu Wai; Krause, Michael; Savan, Alan; Thienhaus, Sigurd; Koukourakis, Nektarios; Hofmann, Martin R; Ludwig, Alfred

    2011-10-01

    A high-throughput characterization technique based on digital holography for mapping film thickness in thin-film materials libraries was developed. Digital holographic microscopy is used for fully automatic measurements of the thickness of patterned films with nanometer resolution. The method has several significant advantages over conventional stylus profilometry: it is contactless and fast, substrate bending is compensated, and the experimental setup is simple. Patterned films prepared by different combinatorial thin-film approaches were characterized to investigate and demonstrate this method. The results show that this technique is valuable for the quick, reliable and high-throughput determination of the film thickness distribution in combinatorial materials research. Importantly, it can also be applied to thin films that have been structured by shadow masking.

  15. The French press: a repeatable and high-throughput approach to exercising zebrafish (Danio rerio).

    Science.gov (United States)

    Usui, Takuji; Noble, Daniel W A; O'Dea, Rose E; Fangmeier, Melissa L; Lagisz, Malgorzata; Hesselson, Daniel; Nakagawa, Shinichi

    2018-01-01

    Zebrafish are increasingly used as a vertebrate model organism for various traits including swimming performance, obesity and metabolism, necessitating high-throughput protocols to generate standardized phenotypic information. Here, we propose a novel and cost-effective method for exercising zebrafish, using a coffee plunger and magnetic stirrer. To demonstrate the use of this method, we conducted a pilot experiment to show that this simple system provides repeatable estimates of maximal swim performance (intra-class correlation [ICC] = 0.34-0.41) and observe that exercise training of zebrafish on this system significantly increases their maximum swimming speed. We propose this high-throughput and reproducible system as an alternative to traditional linear chamber systems for exercising zebrafish and similarly sized fishes.

  16. Selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi.

    Science.gov (United States)

    Keenan, Martine; Alexander, Paul W; Chaplin, Jason H; Abbott, Michael J; Diao, Hugo; Wang, Zhisen; Best, Wayne M; Perez, Catherine J; Cornwall, Scott M J; Keatley, Sarah K; Thompson, R C Andrew; Charman, Susan A; White, Karen L; Ryan, Eileen; Chen, Gong; Ioset, Jean-Robert; von Geldern, Thomas W; Chatelain, Eric

    2013-10-01

    Inhibitors of Trypanosoma cruzi with novel mechanisms of action are urgently required to diversify the current clinical and preclinical pipelines. Increasing the number and diversity of hits available for assessment at the beginning of the discovery process will help to achieve this aim. We report the evaluation of multiple hits generated from a high-throughput screen to identify inhibitors of T. cruzi and from these studies the discovery of two novel series currently in lead optimization. Lead compounds from these series potently and selectively inhibit growth of T. cruzi in vitro and the most advanced compound is orally active in a subchronic mouse model of T. cruzi infection. High-throughput screening of novel compound collections has an important role to play in diversifying the trypanosomatid drug discovery portfolio. A new T. cruzi inhibitor series with good drug-like properties and promising in vivo efficacy has been identified through this process.

  17. Determining the optimal size of small molecule mixtures for high throughput NMR screening

    International Nuclear Information System (INIS)

    Mercier, Kelly A.; Powers, Robert

    2005-01-01

    High-throughput screening (HTS) using NMR spectroscopy has become a common component of the drug discovery effort and is widely used throughout the pharmaceutical industry. NMR provides additional information about the nature of small molecule-protein interactions compared to traditional HTS methods. In order to achieve comparable efficiency, small molecules are often screened as mixtures in NMR-based assays. Nevertheless, an analysis of the efficiency of mixtures and a corresponding determination of the optimum mixture size (OMS) that minimizes the amount of material and instrumentation time required for an NMR screen has been lacking. A model for calculating OMS based on the application of the hypergeometric distribution function to determine the probability of a 'hit' for various mixture sizes and hit rates is presented. An alternative method for the deconvolution of large screening mixtures is also discussed. These methods have been applied in a high-throughput NMR screening assay using a small, directed library

  18. High-throughput screening of small molecule libraries using SAMDI mass spectrometry.

    Science.gov (United States)

    Gurard-Levin, Zachary A; Scholle, Michael D; Eisenberg, Adam H; Mrksich, Milan

    2011-07-11

    High-throughput screening is a common strategy used to identify compounds that modulate biochemical activities, but many approaches depend on cumbersome fluorescent reporters or antibodies and often produce false-positive hits. The development of "label-free" assays addresses many of these limitations, but current approaches still lack the throughput needed for applications in drug discovery. This paper describes a high-throughput, label-free assay that combines self-assembled monolayers with mass spectrometry, in a technique called SAMDI, as a tool for screening libraries of 100,000 compounds in one day. This method is fast, has high discrimination, and is amenable to a broad range of chemical and biological applications.

  19. High-throughput screening assay of hepatitis C virus helicase inhibitors using fluorescence-quenching phenomenon

    International Nuclear Information System (INIS)

    Tani, Hidenori; Akimitsu, Nobuyoshi; Fujita, Osamu; Matsuda, Yasuyoshi; Miyata, Ryo; Tsuneda, Satoshi; Igarashi, Masayuki; Sekiguchi, Yuji; Noda, Naohiro

    2009-01-01

    We have developed a novel high-throughput screening assay of hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase inhibitors using the fluorescence-quenching phenomenon via photoinduced electron transfer between fluorescent dyes and guanine bases. We prepared double-stranded DNA (dsDNA) with a 5'-fluorescent-dye (BODIPY FL)-labeled strand hybridized with a complementary strand, the 3'-end of which has guanine bases. When dsDNA is unwound by helicase, the dye emits fluorescence owing to its release from the guanine bases. Our results demonstrate that this assay is suitable for quantitative assay of HCV NS3 helicase activity and useful for high-throughput screening for inhibitors. Furthermore, we applied this assay to the screening for NS3 helicase inhibitors from cell extracts of microorganisms, and found several cell extracts containing potential inhibitors.

  20. High-throughput shotgun lipidomics by quadrupole time-of-flight mass spectrometry

    DEFF Research Database (Denmark)

    Ståhlman, Marcus; Ejsing, Christer S.; Tarasov, Kirill

    2009-01-01

    Technological advances in mass spectrometry and meticulous method development have produced several shotgun lipidomic approaches capable of characterizing lipid species by direct analysis of total lipid extracts. Shotgun lipidomics by hybrid quadrupole time-of-flight mass spectrometry allows...... the absolute quantification of hundreds of molecular glycerophospholipid species, glycerolipid species, sphingolipid species and sterol lipids. Future applications in clinical cohort studies demand detailed lipid molecule information and the application of high-throughput lipidomics platforms. In this review...... we describe a novel high-throughput shotgun lipidomic platform based on 96-well robot-assisted lipid extraction, automated sample infusion by mircofluidic-based nanoelectrospray ionization, and quantitative multiple precursor ion scanning analysis on a quadrupole time-of-flight mass spectrometer...

  1. Multiplex High-Throughput Targeted Proteomic Assay To Identify Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Baud, Anna; Wessely, Frank; Mazzacuva, Francesca; McCormick, James; Camuzeaux, Stephane; Heywood, Wendy E; Little, Daniel; Vowles, Jane; Tuefferd, Marianne; Mosaku, Olukunbi; Lako, Majlinda; Armstrong, Lyle; Webber, Caleb; Cader, M Zameel; Peeters, Pieter; Gissen, Paul; Cowley, Sally A; Mills, Kevin

    2017-02-21

    Induced pluripotent stem cells have great potential as a human model system in regenerative medicine, disease modeling, and drug screening. However, their use in medical research is hampered by laborious reprogramming procedures that yield low numbers of induced pluripotent stem cells. For further applications in research, only the best, competent clones should be used. The standard assays for pluripotency are based on genomic approaches, which take up to 1 week to perform and incur significant cost. Therefore, there is a need for a rapid and cost-effective assay able to distinguish between pluripotent and nonpluripotent cells. Here, we describe a novel multiplexed, high-throughput, and sensitive peptide-based multiple reaction monitoring mass spectrometry assay, allowing for the identification and absolute quantitation of multiple core transcription factors and pluripotency markers. This assay provides simpler and high-throughput classification into either pluripotent or nonpluripotent cells in 7 min analysis while being more cost-effective than conventional genomic tests.

  2. Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis.

    Science.gov (United States)

    Mei, Feng; Fancy, Stephen P J; Shen, Yun-An A; Niu, Jianqin; Zhao, Chao; Presley, Bryan; Miao, Edna; Lee, Seonok; Mayoral, Sonia R; Redmond, Stephanie A; Etxeberria, Ainhoa; Xiao, Lan; Franklin, Robin J M; Green, Ari; Hauser, Stephen L; Chan, Jonah R

    2014-08-01

    Functional screening for compounds that promote remyelination represents a major hurdle in the development of rational therapeutics for multiple sclerosis. Screening for remyelination is problematic, as myelination requires the presence of axons. Standard methods do not resolve cell-autonomous effects and are not suited for high-throughput formats. Here we describe a binary indicant for myelination using micropillar arrays (BIMA). Engineered with conical dimensions, micropillars permit resolution of the extent and length of membrane wrapping from a single two-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for detection of concentric wrapping observed as 'rings' of myelin. The platform is formatted in 96-well plates, amenable to semiautomated random acquisition and automated detection and quantification. Upon screening 1,000 bioactive molecules, we identified a cluster of antimuscarinic compounds that enhance oligodendrocyte differentiation and remyelination. Our findings demonstrate a new high-throughput screening platform for potential regenerative therapeutics in multiple sclerosis.

  3. Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS)

    Energy Technology Data Exchange (ETDEWEB)

    Hura, Greg L.; Menon, Angeli L.; Hammel, Michal; Rambo, Robert P.; Poole II, Farris L.; Tsutakawa, Susan E.; Jenney Jr, Francis E.; Classen, Scott; Frankel, Kenneth A.; Hopkins, Robert C.; Yang, Sungjae; Scott, Joseph W.; Dillard, Bret D.; Adams, Michael W. W.; Tainer, John A.

    2009-07-20

    We present an efficient pipeline enabling high-throughput analysis of protein structure in solution with small angle X-ray scattering (SAXS). Our SAXS pipeline combines automated sample handling of microliter volumes, temperature and anaerobic control, rapid data collection and data analysis, and couples structural analysis with automated archiving. We subjected 50 representative proteins, mostly from Pyrococcus furiosus, to this pipeline and found that 30 were multimeric structures in solution. SAXS analysis allowed us to distinguish aggregated and unfolded proteins, define global structural parameters and oligomeric states for most samples, identify shapes and similar structures for 25 unknown structures, and determine envelopes for 41 proteins. We believe that high-throughput SAXS is an enabling technology that may change the way that structural genomics research is done.

  4. A high-throughput, multi-channel photon-counting detector with picosecond timing

    CERN Document Server

    Lapington, J S; Miller, G M; Ashton, T J R; Jarron, P; Despeisse, M; Powolny, F; Howorth, J; Milnes, J

    2009-01-01

    High-throughput photon counting with high time resolution is a niche application area where vacuum tubes can still outperform solid-state devices. Applications in the life sciences utilizing time-resolved spectroscopies, particularly in the growing field of proteomics, will benefit greatly from performance enhancements in event timing and detector throughput. The HiContent project is a collaboration between the University of Leicester Space Research Centre, the Microelectronics Group at CERN, Photek Ltd., and end-users at the Gray Cancer Institute and the University of Manchester. The goal is to develop a detector system specifically designed for optical proteomics, capable of high content (multi-parametric) analysis at high throughput. The HiContent detector system is being developed to exploit this niche market. It combines multi-channel, high time resolution photon counting in a single miniaturized detector system with integrated electronics. The combination of enabling technologies; small pore microchanne...

  5. Fabrication of combinatorial nm-planar electrode array for high throughput evaluation of organic semiconductors

    International Nuclear Information System (INIS)

    Haemori, M.; Edura, T.; Tsutsui, K.; Itaka, K.; Wada, Y.; Koinuma, H.

    2006-01-01

    We have fabricated a combinatorial nm-planar electrode array by using photolithography and chemical mechanical polishing processes for high throughput electrical evaluation of organic devices. Sub-nm precision was achieved with respect to the average level difference between each pair of electrodes and a dielectric layer. The insulating property between the electrodes is high enough to measure I-V characteristics of organic semiconductors. Bottom-contact field-effect-transistors (FETs) of pentacene were fabricated on this electrode array by use of molecular beam epitaxy. It was demonstrated that the array could be used as a pre-patterned device substrate for high throughput screening of the electrical properties of organic semiconductors

  6. High-throughput Sequencing Based Immune Repertoire Study during Infectious Disease

    Directory of Open Access Journals (Sweden)

    Dongni Hou

    2016-08-01

    Full Text Available The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. The immune repertoire, the collection of T and B cells with functional diversity in the circulatory system at any given time, is dynamic and reflects the essence of immune selectivity. In this article, we review the recent advances in immune repertoire study of infectious diseases that achieved by traditional techniques and high-throughput sequencing techniques. High-throughput sequencing techniques enable the determination of complementary regions of lymphocyte receptors with unprecedented efficiency and scale. This progress in methodology enhances the understanding of immunologic changes during pathogen challenge, and also provides a basis for further development of novel diagnostic markers, immunotherapies and vaccines.

  7. Data for automated, high-throughput microscopy analysis of intracellular bacterial colonies using spot detection.

    Science.gov (United States)

    Ernstsen, Christina L; Login, Frédéric H; Jensen, Helene H; Nørregaard, Rikke; Møller-Jensen, Jakob; Nejsum, Lene N

    2017-10-01

    Quantification of intracellular bacterial colonies is useful in strategies directed against bacterial attachment, subsequent cellular invasion and intracellular proliferation. An automated, high-throughput microscopy-method was established to quantify the number and size of intracellular bacterial colonies in infected host cells (Detection and quantification of intracellular bacterial colonies by automated, high-throughput microscopy, Ernstsen et al., 2017 [1]). The infected cells were imaged with a 10× objective and number of intracellular bacterial colonies, their size distribution and the number of cell nuclei were automatically quantified using a spot detection-tool. The spot detection-output was exported to Excel, where data analysis was performed. In this article, micrographs and spot detection data are made available to facilitate implementation of the method.

  8. Accurate Classification of Protein Subcellular Localization from High-Throughput Microscopy Images Using Deep Learning

    Directory of Open Access Journals (Sweden)

    Tanel Pärnamaa

    2017-05-01

    Full Text Available High-throughput microscopy of many single cells generates high-dimensional data that are far from straightforward to analyze. One important problem is automatically detecting the cellular compartment where a fluorescently-tagged protein resides, a task relatively simple for an experienced human, but difficult to automate on a computer. Here, we train an 11-layer neural network on data from mapping thousands of yeast proteins, achieving per cell localization classification accuracy of 91%, and per protein accuracy of 99% on held-out images. We confirm that low-level network features correspond to basic image characteristics, while deeper layers separate localization classes. Using this network as a feature calculator, we train standard classifiers that assign proteins to previously unseen compartments after observing only a small number of training examples. Our results are the most accurate subcellular localization classifications to date, and demonstrate the usefulness of deep learning for high-throughput microscopy.

  9. High-throughput metagenomic technologies for complex microbial community analysis: open and closed formats.

    Science.gov (United States)

    Zhou, Jizhong; He, Zhili; Yang, Yunfeng; Deng, Ye; Tringe, Susannah G; Alvarez-Cohen, Lisa

    2015-01-27

    Understanding the structure, functions, activities and dynamics of microbial communities in natural environments is one of the grand challenges of 21st century science. To address this challenge, over the past decade, numerous technologies have been developed for interrogating microbial communities, of which some are amenable to exploratory work (e.g., high-throughput sequencing and phenotypic screening) and others depend on reference genes or genomes (e.g., phylogenetic and functional gene arrays). Here, we provide a critical review and synthesis of the most commonly applied "open-format" and "closed-format" detection technologies. We discuss their characteristics, advantages, and disadvantages within the context of environmental applications and focus on analysis of complex microbial systems, such as those in soils, in which diversity is high and reference genomes are few. In addition, we discuss crucial issues and considerations associated with applying complementary high-throughput molecular technologies to address important ecological questions. Copyright © 2015 Zhou et al.

  10. High-Throughput Screening of a Luciferase Reporter of Gene Silencing on the Inactive X Chromosome.

    Science.gov (United States)

    Keegan, Alissa; Plath, Kathrin; Damoiseaux, Robert

    2018-01-01

    Assays of luciferase gene activity are a sensitive and quantitative reporter system suited to high-throughput screening. We adapted a luciferase assay to a screening strategy for identifying factors that reactivate epigenetically silenced genes. This epigenetic luciferase reporter is subject to endogenous gene silencing mechanisms on the inactive X chromosome (Xi) in primary mouse cells and thus captures the multilayered nature of chromatin silencing in development. Here, we describe the optimization of an Xi-linked luciferase reactivation assay in 384-well format and adaptation of the assay for high-throughput siRNA and chemical screening. Xi-luciferase reactivation screening has applications in stem cell biology and cancer therapy. We have used the approach described here to identify chromatin-modifying proteins and to identify drug combinations that enhance the gene reactivation activity of the DNA demethylating drug 5-aza-2'-deoxycytidine.

  11. High-throughput tri-colour flow cytometry technique to assess Plasmodium falciparum parasitaemia in bioassays

    DEFF Research Database (Denmark)

    Tiendrebeogo, Regis W; Adu, Bright; Singh, Susheel K

    2014-01-01

    BACKGROUND: Unbiased flow cytometry-based methods have become the technique of choice in many laboratories for high-throughput, accurate assessments of malaria parasites in bioassays. A method to quantify live parasites based on mitotracker red CMXRos was recently described but consistent...... distinction of early ring stages of Plasmodium falciparum from uninfected red blood cells (uRBC) remains a challenge. METHODS: Here, a high-throughput, three-parameter (tri-colour) flow cytometry technique based on mitotracker red dye, the nucleic acid dye coriphosphine O (CPO) and the leucocyte marker CD45...... for enumerating live parasites in bioassays was developed. The technique was applied to estimate the specific growth inhibition index (SGI) in the antibody-dependent cellular inhibition (ADCI) assay and compared to parasite quantification by microscopy and mitotracker red staining. The Bland-Altman analysis...

  12. Fluorescence-based high-throughput screening of dicer cleavage activity.

    Science.gov (United States)

    Podolska, Katerina; Sedlak, David; Bartunek, Petr; Svoboda, Petr

    2014-03-01

    Production of small RNAs by ribonuclease III Dicer is a key step in microRNA and RNA interference pathways, which employ Dicer-produced small RNAs as sequence-specific silencing guides. Further studies and manipulations of microRNA and RNA interference pathways would benefit from identification of small-molecule modulators. Here, we report a study of a fluorescence-based in vitro Dicer cleavage assay, which was adapted for high-throughput screening. The kinetic assay can be performed under single-turnover conditions (35 nM substrate and 70 nM Dicer) in a small volume (5 µL), which makes it suitable for high-throughput screening in a 1536-well format. As a proof of principle, a small library of bioactive compounds was analyzed, demonstrating potential of the assay.

  13. Multiple and high-throughput droplet reactions via combination of microsampling technique and microfluidic chip

    KAUST Repository

    Wu, Jinbo

    2012-11-20

    Microdroplets offer unique compartments for accommodating a large number of chemical and biological reactions in tiny volume with precise control. A major concern in droplet-based microfluidics is the difficulty to address droplets individually and achieve high throughput at the same time. Here, we have combined an improved cartridge sampling technique with a microfluidic chip to perform droplet screenings and aggressive reaction with minimal (nanoliter-scale) reagent consumption. The droplet composition, distance, volume (nanoliter to subnanoliter scale), number, and sequence could be precisely and digitally programmed through the improved sampling technique, while sample evaporation and cross-contamination are effectively eliminated. Our combined device provides a simple model to utilize multiple droplets for various reactions with low reagent consumption and high throughput. © 2012 American Chemical Society.

  14. Accurate Classification of Protein Subcellular Localization from High-Throughput Microscopy Images Using Deep Learning.

    Science.gov (United States)

    Pärnamaa, Tanel; Parts, Leopold

    2017-05-05

    High-throughput microscopy of many single cells generates high-dimensional data that are far from straightforward to analyze. One important problem is automatically detecting the cellular compartment where a fluorescently-tagged protein resides, a task relatively simple for an experienced human, but difficult to automate on a computer. Here, we train an 11-layer neural network on data from mapping thousands of yeast proteins, achieving per cell localization classification accuracy of 91%, and per protein accuracy of 99% on held-out images. We confirm that low-level network features correspond to basic image characteristics, while deeper layers separate localization classes. Using this network as a feature calculator, we train standard classifiers that assign proteins to previously unseen compartments after observing only a small number of training examples. Our results are the most accurate subcellular localization classifications to date, and demonstrate the usefulness of deep learning for high-throughput microscopy. Copyright © 2017 Parnamaa and Parts.

  15. High throughput route selection in multi-rate wireless mesh networks

    Institute of Scientific and Technical Information of China (English)

    WEI Yi-fei; GUO Xiang-li; SONG Mei; SONG Jun-de

    2008-01-01

    Most existing Ad-hoc routing protocols use the shortest path algorithm with a hop count metric to select paths. It is appropriate in single-rate wireless networks, but has a tendency to select paths containing long-distance links that have low data rates and reduced reliability in multi-rate networks. This article introduces a high throughput routing algorithm utilizing the multi-rate capability and some mesh characteristics in wireless fidelity (WiFi) mesh networks. It uses the medium access control (MAC) transmission time as the routing metric, which is estimated by the information passed up from the physical layer. When the proposed algorithm is adopted, the Ad-hoc on-demand distance vector (AODV) routing can be improved as high throughput AODV (HT-AODV). Simulation results show that HT-AODV is capable of establishing a route that has high data-rate, short end-to-end delay and great network throughput.

  16. From Classical to High Throughput Screening Methods for Feruloyl Esterases: A Review.

    Science.gov (United States)

    Ramírez-Velasco, Lorena; Armendáriz-Ruiz, Mariana; Rodríguez-González, Jorge Alberto; Müller-Santos, Marcelo; Asaff-Torres, Ali; Mateos-Díaz, Juan Carlos

    2016-01-01

    Feruloyl esterases (FAEs) are a diverse group of hydrolases widely distributed in plants and microorganisms which catalyzes the cleavage and formation of ester bonds between plant cell wall polysaccharides and phenolic acids. FAEs have gained importance in biofuel, medicine and food industries due to their capability of acting on a large range of substrates for cleaving ester bonds and synthesizing highadded value molecules through esterification and transesterification reactions. During the past two decades extensive studies have been carried out on the production, characterization and classification of FAEs, however only a few reports of suitable High Throughput Screening assays for this kind of enzymes have been reported. This review is focused on a concise but complete revision of classical to High Throughput Screening methods for FAEs, highlighting its advantages and disadvantages, and finally suggesting future perspectives for this important research field.

  17. Psi4NumPy: An Interactive Quantum Chemistry Programming Environment for Reference Implementations and Rapid Development.

    Science.gov (United States)

    Smith, Daniel G A; Burns, Lori A; Sirianni, Dominic A; Nascimento, Daniel R; Kumar, Ashutosh; James, Andrew M; Schriber, Jeffrey B; Zhang, Tianyuan; Zhang, Boyi; Abbott, Adam S; Berquist, Eric J; Lechner, Marvin H; Cunha, Leonardo A; Heide, Alexander G; Waldrop, Jonathan M; Takeshita, Tyler Y; Alenaizan, Asem; Neuhauser, Daniel; King, Rollin A; Simmonett, Andrew C; Turney, Justin M; Schaefer, Henry F; Evangelista, Francesco A; DePrince, A Eugene; Crawford, T Daniel; Patkowski, Konrad; Sherrill, C David

    2018-06-11

    Psi4NumPy demonstrates the use of efficient computational kernels from the open-source Psi4 program through the popular NumPy library for linear algebra in Python to facilitate the rapid development of clear, understandable Python computer code for new quantum chemical methods, while maintaining a relatively low execution time. Using these tools, reference implementations have been created for a number of methods, including self-consistent field (SCF), SCF response, many-body perturbation theory, coupled-cluster theory, configuration interaction, and symmetry-adapted perturbation theory. Furthermore, several reference codes have been integrated into Jupyter notebooks, allowing background, underlying theory, and formula information to be associated with the implementation. Psi4NumPy tools and associated reference implementations can lower the barrier for future development of quantum chemistry methods. These implementations also demonstrate the power of the hybrid C++/Python programming approach employed by the Psi4 program.

  18. Automated quantum chemistry based molecular dynamics simulations of electron ionization induced fragmentations of the nucleobases Uracil, Thymine, Cytosine, and Guanine.

    Science.gov (United States)

    Grimme, Stefan; Bauer, Christopher Alexander

    2015-01-01

    The gas-phase decomposition pathways of electron ionization (EI)-induced radical cations of the nucleobases uracil, thymine, cytosine, and guanine are investigated by means of mixed quantum-classical molecular dynamics. No preconceived fragmentation channels are used in the calculations. The results compare well to a plethora of experimental and theoretical data for these important biomolecules. With our combined stochastic and dynamic approach, one can access in an unbiased way the energetically available decomposition mechanisms. Additionally, we are able to separate the EI mass spectra of different tautomers of cytosine and guanine. Our method (previously termed quantum chemistry electron ionization mass spectra) reproduces free nucleobase experimental mass spectra well and provides detailed mechanistic in-sight into high-energy unimolecular decomposition processes.

  19. Association Study of Gut Flora in Coronary Heart Disease through High-Throughput Sequencing

    OpenAIRE

    Cui, Li; Zhao, Tingting; Hu, Haibing; Zhang, Wen; Hua, Xiuguo

    2017-01-01

    Objectives. We aimed to explore the impact of gut microbiota in coronary heart disease (CHD) patients through high-throughput sequencing. Methods. A total of 29 CHD in-hospital patients and 35 healthy volunteers as controls were included. Nucleic acids were extracted from fecal samples, followed by ? diversity and principal coordinate analysis (PCoA). Based on unweighted UniFrac distance matrices, unweighted-pair group method with arithmetic mean (UPGMA) trees were created. Results. After dat...

  20. Rapid 2,2'-bicinchoninic-based xylanase assay compatible with high throughput screening

    Science.gov (United States)

    William R. Kenealy; Thomas W. Jeffries

    2003-01-01

    High-throughput screening requires simple assays that give reliable quantitative results. A microplate assay was developed for reducing sugar analysis that uses a 2,2'-bicinchoninic-based protein reagent. Endo-1,4-â-D-xylanase activity against oat spelt xylan was detected at activities of 0.002 to 0.011 IU ml−1. The assay is linear for sugar...

  1. Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to the Channel of Botulinum Neurotoxin

    National Research Council Canada - National Science Library

    Montal, Mauricio

    2006-01-01

    .... The major focus thus far has been the implementation of a reliable and robust high-throughput screen for blockers specific for BoNT using Neuro 2A cells in which BoNTA forms channels with similar properties to those previously characterized in lipid bilayers. The immediate task during the present reporting period involved the detailed characterization of the channel and chaperone activity of BoNTA on Neuro2A cells.

  2. Upscaling and automation of electrophysiology: toward high throughput screening in ion channel drug discovery

    DEFF Research Database (Denmark)

    Asmild, Margit; Oswald, Nicholas; Krzywkowski, Karen M

    2003-01-01

    by developing two lines of automated patch clamp products, a traditional pipette-based system called Apatchi-1, and a silicon chip-based system QPatch. The degree of automation spans from semi-automation (Apatchi-1) where a trained technician interacts with the system in a limited way, to a complete automation...... (QPatch 96) where the system works continuously and unattended until screening of a full compound library is completed. The performance of the systems range from medium to high throughputs....

  3. A High Throughput Ambient Mass Spectrometric Approach to Species Identification and Classification from Chemical Fingerprint Signatures

    OpenAIRE

    Musah, Rabi A.; Espinoza, Edgard O.; Cody, Robert B.; Lesiak, Ashton D.; Christensen, Earl D.; Moore, Hannah E.; Maleknia, Simin; Drijfhout, Falko P.

    2015-01-01

    A high throughput method for species identification and classification through chemometric processing of direct analysis in real time (DART) mass spectrometry-derived fingerprint signatures has been developed. The method entails introduction of samples to the open air space between the DART ion source and the mass spectrometer inlet, with the entire observed mass spectral fingerprint subjected to unsupervised hierarchical clustering processing. A range of both polar and non-polar chemotypes a...

  4. Genecentric: a package to uncover graph-theoretic structure in high-throughput epistasis data

    OpenAIRE

    Gallant, Andrew; Leiserson, Mark DM; Kachalov, Maxim; Cowen, Lenore J; Hescott, Benjamin J

    2013-01-01

    Background New technology has resulted in high-throughput screens for pairwise genetic interactions in yeast and other model organisms. For each pair in a collection of non-essential genes, an epistasis score is obtained, representing how much sicker (or healthier) the double-knockout organism will be compared to what would be expected from the sickness of the component single knockouts. Recent algorithmic work has identified graph-theoretic patterns in this data that can indicate functional ...

  5. High-throughput evaluation of interactions between biomaterials, proteins and cells using patterned superhydrophobic substrates

    OpenAIRE

    Neto, Ana I.; Custódio, Catarina A.; Wenlong Song; Mano, J. F.

    2011-01-01

    We propose a new low cost platform for high-throughput analysis that permits screening the biological performance of independent combinations of biomaterials, cells and culture media. Patterned superhydrophobic flat substrates with controlled wettable spots are used to produce microarray chips for accelerated multiplexing evaluation. This work was partially supported by Fundação para a Ciência e Tecnologia (FCT) under project PTDC/FIS/68517/2006.

  6. Geochip: A high throughput genomic tool for linking community structure to functions

    Energy Technology Data Exchange (ETDEWEB)

    Van Nostrand, Joy D.; Liang, Yuting; He, Zhili; Li, Guanghe; Zhou, Jizhong

    2009-01-30

    GeoChip is a comprehensive functional gene array that targets key functional genes involved in the geochemical cycling of N, C, and P, sulfate reduction, metal resistance and reduction, and contaminant degradation. Studies have shown the GeoChip to be a sensitive, specific, and high-throughput tool for microbial community analysis that has the power to link geochemical processes with microbial community structure. However, several challenges remain regarding the development and applications of microarrays for microbial community analysis.

  7. Computational and statistical methods for high-throughput analysis of post-translational modifications of proteins

    DEFF Research Database (Denmark)

    Schwämmle, Veit; Braga, Thiago Verano; Roepstorff, Peter

    2015-01-01

    The investigation of post-translational modifications (PTMs) represents one of the main research focuses for the study of protein function and cell signaling. Mass spectrometry instrumentation with increasing sensitivity improved protocols for PTM enrichment and recently established pipelines...... for high-throughput experiments allow large-scale identification and quantification of several PTM types. This review addresses the concurrently emerging challenges for the computational analysis of the resulting data and presents PTM-centered approaches for spectra identification, statistical analysis...

  8. Development of Microfluidic Systems Enabling High-Throughput Single-Cell Protein Characterization

    OpenAIRE

    Fan, Beiyuan; Li, Xiufeng; Chen, Deyong; Peng, Hongshang; Wang, Junbo; Chen, Jian

    2016-01-01

    This article reviews recent developments in microfluidic systems enabling high-throughput characterization of single-cell proteins. Four key perspectives of microfluidic platforms are included in this review: (1) microfluidic fluorescent flow cytometry; (2) droplet based microfluidic flow cytometry; (3) large-array micro wells (microengraving); and (4) large-array micro chambers (barcode microchips). We examine the advantages and limitations of each technique and discuss future research oppor...

  9. Automated image alignment for 2D gel electrophoresis in a high-throughput proteomics pipeline.

    Science.gov (United States)

    Dowsey, Andrew W; Dunn, Michael J; Yang, Guang-Zhong

    2008-04-01

    The quest for high-throughput proteomics has revealed a number of challenges in recent years. Whilst substantial improvements in automated protein separation with liquid chromatography and mass spectrometry (LC/MS), aka 'shotgun' proteomics, have been achieved, large-scale open initiatives such as the Human Proteome Organization (HUPO) Brain Proteome Project have shown that maximal proteome coverage is only possible when LC/MS is complemented by 2D gel electrophoresis (2-DE) studies. Moreover, both separation methods require automated alignment and differential analysis to relieve the bioinformatics bottleneck and so make high-throughput protein biomarker discovery a reality. The purpose of this article is to describe a fully automatic image alignment framework for the integration of 2-DE into a high-throughput differential expression proteomics pipeline. The proposed method is based on robust automated image normalization (RAIN) to circumvent the drawbacks of traditional approaches. These use symbolic representation at the very early stages of the analysis, which introduces persistent errors due to inaccuracies in modelling and alignment. In RAIN, a third-order volume-invariant B-spline model is incorporated into a multi-resolution schema to correct for geometric and expression inhomogeneity at multiple scales. The normalized images can then be compared directly in the image domain for quantitative differential analysis. Through evaluation against an existing state-of-the-art method on real and synthetically warped 2D gels, the proposed analysis framework demonstrates substantial improvements in matching accuracy and differential sensitivity. High-throughput analysis is established through an accelerated GPGPU (general purpose computation on graphics cards) implementation. Supplementary material, software and images used in the validation are available at http://www.proteomegrid.org/rain/.

  10. Fluorescence-based high-throughput screening of dicer cleavage activity

    Czech Academy of Sciences Publication Activity Database

    Podolská, Kateřina; Sedlák, David; Bartůněk, Petr; Svoboda, Petr

    2014-01-01

    Roč. 19, č. 3 (2014), s. 417-426 ISSN 1087-0571 R&D Projects: GA ČR GA13-29531S; GA MŠk(CZ) LC06077; GA MŠk LM2011022 Grant - others:EMBO(DE) 1483 Institutional support: RVO:68378050 Keywords : Dicer * siRNA * high-throughput screening Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.423, year: 2014

  11. High-throughput screening of tick-borne pathogens in Europe

    DEFF Research Database (Denmark)

    Michelet, Lorraine; Delannoy, Sabine; Devillers, Elodie

    2014-01-01

    was conducted on 7050 Ixodes ricinus nymphs collected from France, Denmark, and the Netherlands using a powerful new high-throughput approach. This advanced methodology permitted the simultaneous detection of 25 bacterial, and 12 parasitic species (including; Borrelia, Anaplasma, Ehrlichia, Rickettsia......, Bartonella, Candidatus Neoehrlichia, Coxiella, Francisella, Babesia, and Theileria genus) across 94 samples. We successfully determined the prevalence of expected (Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Rickettsia helvetica, Candidatus Neoehrlichia mikurensis, Babesia divergens, Babesia...

  12. Targeted DNA Methylation Analysis by High Throughput Sequencing in Porcine Peri-attachment Embryos

    OpenAIRE

    MORRILL, Benson H.; COX, Lindsay; WARD, Anika; HEYWOOD, Sierra; PRATHER, Randall S.; ISOM, S. Clay

    2013-01-01

    Abstract The purpose of this experiment was to implement and evaluate the effectiveness of a next-generation sequencing-based method for DNA methylation analysis in porcine embryonic samples. Fourteen discrete genomic regions were amplified by PCR using bisulfite-converted genomic DNA derived from day 14 in vivo-derived (IVV) and parthenogenetic (PA) porcine embryos as template DNA. Resulting PCR products were subjected to high-throughput sequencing using the Illumina Genome Analyzer IIx plat...

  13. High-throughput screening of metal-porphyrin-like graphenes for selective capture of carbon dioxide

    OpenAIRE

    Hyeonhu Bae; Minwoo Park; Byungryul Jang; Yura Kang; Jinwoo Park; Hosik Lee; Haegeun Chung; ChiHye Chung; Suklyun Hong; Yongkyung Kwon; Boris I. Yakobson; Hoonkyung Lee

    2016-01-01

    Nanostructured materials, such as zeolites and metal-organic frameworks, have been considered to capture CO2. However, their application has been limited largely because they exhibit poor selectivity for flue gases and low capture capacity under low pressures. We perform a high-throughput screening for selective CO2 capture from flue gases by using first principles thermodynamics. We find that elements with empty d orbitals selectively attract CO2 from gaseous mixtures under low CO2 pressures...

  14. High Throughput Single-cell and Multiple-cell Micro-encapsulation

    OpenAIRE

    Lagus, Todd P.; Edd, Jon F.

    2012-01-01

    Microfluidic encapsulation methods have been previously utilized to capture cells in picoliter-scale aqueous, monodisperse drops, providing confinement from a bulk fluid environment with applications in high throughput screening, cytometry, and mass spectrometry. We describe a method to not only encapsulate single cells, but to repeatedly capture a set number of cells (here we demonstrate one- and two-cell encapsulation) to study both isolation and the interactions between cells in groups of ...

  15. High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes.

    Science.gov (United States)

    Lorenz, Daniel A; Song, James M; Garner, Amanda L

    2015-01-21

    MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.

  16. Chemistry

    International Nuclear Information System (INIS)

    Ferris, L.M.

    1975-01-01

    Research and development activities dealing with the chemical problems related to design and ultimate operation of molten-salt reactor systems are described. An experimental test stand was constructed to expose metallurgical test specimens to Te 2 vapor at defined temperatures and deposition rates. To better define the chemistry of fluoroborate coolant, several aspects are being investigated. The behavior of hydroxy and oxy compounds in molten NaBF 4 is being investigated to define reactions and compounds that may be involved in corrosion and/or could be involved in methods for trapping tritium. Two corrosion products of Hastelloy N, Na 3 CrF 6 and Na 5 Cr 3 F 14 , were identified from fluoroborate systems. The evaluation of fluoroborate and alternate coolants continued. Research on the behavior of hydrogen and its isotopes is summarized. The solubilities of hydrogen, deuterium, and helium in Li 2 BeF 4 are very low. The sorption of tritium on graphite was found to be significant (a few milligrams of tritium per kilogram of graphite), possibly providing a means of sequestering a portion of the tritium produced. Development of analytical methods continued with emphasis on voltammetric and spectrophotometric techniques for the in-line analysis of corrosion products such as Fe 2+ and Cr 3+ and the determination of the U 3+ /U 4+ ratio in MSBR fuel salt. Similar studies were conducted with the NaBF 4 --NaF coolant salt. Information developed during the previous operation of the CSTF has been assessed and used to formulate plans for evaluation of in-line analytical methods in future CSTF operations. Electroanalytical and spectrophotometric research suggests that an electroactive protonic species is present in molten NaBF 4 --NaF, and that this species rapidly equilibrates with a volatile proton-containing species. Data obtained from the CSTF indicated that tritium was concentrated in the volatile species. (JGB)

  17. High-throughput micro-scale cultivations and chromatography modeling: Powerful tools for integrated process development.

    Science.gov (United States)

    Baumann, Pascal; Hahn, Tobias; Hubbuch, Jürgen

    2015-10-01

    Upstream processes are rather complex to design and the productivity of cells under suitable cultivation conditions is hard to predict. The method of choice for examining the design space is to execute high-throughput cultivation screenings in micro-scale format. Various predictive in silico models have been developed for many downstream processes, leading to a reduction of time and material costs. This paper presents a combined optimization approach based on high-throughput micro-scale cultivation experiments and chromatography modeling. The overall optimized system must not necessarily be the one with highest product titers, but the one resulting in an overall superior process performance in up- and downstream. The methodology is presented in a case study for the Cherry-tagged enzyme Glutathione-S-Transferase from Escherichia coli SE1. The Cherry-Tag™ (Delphi Genetics, Belgium) which can be fused to any target protein allows for direct product analytics by simple VIS absorption measurements. High-throughput cultivations were carried out in a 48-well format in a BioLector micro-scale cultivation system (m2p-Labs, Germany). The downstream process optimization for a set of randomly picked upstream conditions producing high yields was performed in silico using a chromatography modeling software developed in-house (ChromX). The suggested in silico-optimized operational modes for product capturing were validated subsequently. The overall best system was chosen based on a combination of excellent up- and downstream performance. © 2015 Wiley Periodicals, Inc.

  18. Modular high-throughput test stand for versatile screening of thin-film materials libraries

    International Nuclear Information System (INIS)

    Thienhaus, Sigurd; Hamann, Sven; Ludwig, Alfred

    2011-01-01

    Versatile high-throughput characterization tools are required for the development of new materials using combinatorial techniques. Here, we describe a modular, high-throughput test stand for the screening of thin-film materials libraries, which can carry out automated electrical, magnetic and magnetoresistance measurements in the temperature range of −40 to 300 °C. As a proof of concept, we measured the temperature-dependent resistance of Fe–Pd–Mn ferromagnetic shape-memory alloy materials libraries, revealing reversible martensitic transformations and the associated transformation temperatures. Magneto-optical screening measurements of a materials library identify ferromagnetic samples, whereas resistivity maps support the discovery of new phases. A distance sensor in the same setup allows stress measurements in materials libraries deposited on cantilever arrays. A combination of these methods offers a fast and reliable high-throughput characterization technology for searching for new materials. Using this approach, a composition region has been identified in the Fe–Pd–Mn system that combines ferromagnetism and martensitic transformation.

  19. High throughput electrospinning of high-quality nanofibers via an aluminum disk spinneret

    Science.gov (United States)

    Zheng, Guokuo

    In this work, a simple and efficient needleless high throughput electrospinning process using an aluminum disk spinneret with 24 holes is described. Electrospun mats produced by this setup consisted of fine fibers (nano-sized) of the highest quality while the productivity (yield) was many times that obtained from conventional single-needle electrospinning. The goal was to produce scaled-up amounts of the same or better quality nanofibers under variable concentration, voltage, and the working distance than those produced with the single needle lab setting. The fiber mats produced were either polymer or ceramic (such as molybdenum trioxide nanofibers). Through experimentation the optimum process conditions were defined to be: 24 kilovolt, a distance to collector of 15cm. More diluted solutions resulted in smaller diameter fibers. Comparing the morphologies of the nanofibers of MoO3 produced by both the traditional and the high throughput set up it was found that they were very similar. Moreover, the nanofibers production rate is nearly 10 times than that of traditional needle electrospinning. Thus, the high throughput process has the potential to become an industrial nanomanufacturing process and the materials processed by it may be used as filtration devices, in tissue engineering, and as sensors.

  20. The application of the high throughput sequencing technology in the transposable elements.

    Science.gov (United States)

    Liu, Zhen; Xu, Jian-hong

    2015-09-01

    High throughput sequencing technology has dramatically improved the efficiency of DNA sequencing, and decreased the costs to a great extent. Meanwhile, this technology usually has advantages of better specificity, higher sensitivity and accuracy. Therefore, it has been applied to the research on genetic variations, transcriptomics and epigenomics. Recently, this technology has been widely employed in the studies of transposable elements and has achieved fruitful results. In this review, we summarize the application of high throughput sequencing technology in the fields of transposable elements, including the estimation of transposon content, preference of target sites and distribution, insertion polymorphism and population frequency, identification of rare copies, transposon horizontal transfers as well as transposon tagging. We also briefly introduce the major common sequencing strategies and algorithms, their advantages and disadvantages, and the corresponding solutions. Finally, we envision the developing trends of high throughput sequencing technology, especially the third generation sequencing technology, and its application in transposon studies in the future, hopefully providing a comprehensive understanding and reference for related scientific researchers.

  1. Large-scale DNA Barcode Library Generation for Biomolecule Identification in High-throughput Screens.

    Science.gov (United States)

    Lyons, Eli; Sheridan, Paul; Tremmel, Georg; Miyano, Satoru; Sugano, Sumio

    2017-10-24

    High-throughput screens allow for the identification of specific biomolecules with characteristics of interest. In barcoded screens, DNA barcodes are linked to target biomolecules in a manner allowing for the target molecules making up a library to be identified by sequencing the DNA barcodes using Next Generation Sequencing. To be useful in experimental settings, the DNA barcodes in a library must satisfy certain constraints related to GC content, homopolymer length, Hamming distance, and blacklisted subsequences. Here we report a novel framework to quickly generate large-scale libraries of DNA barcodes for use in high-throughput screens. We show that our framework dramatically reduces the computation time required to generate large-scale DNA barcode libraries, compared with a naїve approach to DNA barcode library generation. As a proof of concept, we demonstrate that our framework is able to generate a library consisting of one million DNA barcodes for use in a fragment antibody phage display screening experiment. We also report generating a general purpose one billion DNA barcode library, the largest such library yet reported in literature. Our results demonstrate the value of our novel large-scale DNA barcode library generation framework for use in high-throughput screening applications.

  2. An Automated High Throughput Proteolysis and Desalting Platform for Quantitative Proteomic Analysis

    Directory of Open Access Journals (Sweden)

    Albert-Baskar Arul

    2013-06-01

    Full Text Available Proteomics for biomarker validation needs high throughput instrumentation to analyze huge set of clinical samples for quantitative and reproducible analysis at a minimum time without manual experimental errors. Sample preparation, a vital step in proteomics plays a major role in identification and quantification of proteins from biological samples. Tryptic digestion a major check point in sample preparation for mass spectrometry based proteomics needs to be more accurate with rapid processing time. The present study focuses on establishing a high throughput automated online system for proteolytic digestion and desalting of proteins from biological samples quantitatively and qualitatively in a reproducible manner. The present study compares online protein digestion and desalting of BSA with conventional off-line (in-solution method and validated for real time sample for reproducibility. Proteins were identified using SEQUEST data base search engine and the data were quantified using IDEALQ software. The present study shows that the online system capable of handling high throughput samples in 96 well formats carries out protein digestion and peptide desalting efficiently in a reproducible and quantitative manner. Label free quantification showed clear increase of peptide quantities with increase in concentration with much linearity compared to off line method. Hence we would like to suggest that inclusion of this online system in proteomic pipeline will be effective in quantification of proteins in comparative proteomics were the quantification is really very crucial.

  3. A high-throughput surface plasmon resonance biosensor based on differential interferometric imaging

    International Nuclear Information System (INIS)

    Wang, Daqian; Ding, Lili; Zhang, Wei; Zhang, Enyao; Yu, Xinglong; Luo, Zhaofeng; Ou, Huichao

    2012-01-01

    A new high-throughput surface plasmon resonance (SPR) biosensor based on differential interferometric imaging is reported. The two SPR interferograms of the sensing surface are imaged on two CCD cameras. The phase difference between the two interferograms is 180°. The refractive index related factor (RIRF) of the sensing surface is calculated from the two simultaneously acquired interferograms. The simulation results indicate that the RIRF exhibits a linear relationship with the refractive index of the sensing surface and is unaffected by the noise, drift and intensity distribution of the light source. The affinity and kinetic information can be extracted in real time from continuously acquired RIRF distributions. The results of refractometry experiments show that the dynamic detection range of SPR differential interferometric imaging system can be over 0.015 refractive index unit (RIU). High refractive index resolution is down to 0.45 RU (1 RU = 1 × 10 −6 RIU). Imaging and protein microarray experiments demonstrate the ability of high-throughput detection. The aptamer experiments demonstrate that the SPR sensor based on differential interferometric imaging has a great capability to be implemented for high-throughput aptamer kinetic evaluation. These results suggest that this biosensor has the potential to be utilized in proteomics and drug discovery after further improvement. (paper)

  4. Evaluation of Capacity on a High Throughput Vol-oxidizer for Operability

    International Nuclear Information System (INIS)

    Kim, Young Hwan; Park, Geun Il; Lee, Jung Won; Jung, Jae Hoo; Kim, Ki Ho; Lee, Yong Soon; Lee, Do Youn; Kim, Su Sung

    2010-01-01

    KAERI is developing a pyro-process. As a piece of process equipment, a high throughput vol-oxidizer which can handle a several tens kg HM/batch was developed to supply U 3 O 8 powders to an electrolytic reduction(ER) reactor. To increase the reduction yield, UO 2 pellets should be converted into uniform powders. In this paper, we aim at the evaluation of a high throughput vol-oxidizer for operability. The evaluation consisted of 3 targets, a mechanical motion test, a heating test and hull separation test. In order to test a high throughput vol-oxidizer, By using a control system, mechanical motion tests of the vol-oxidizer were conducted, and heating rates were analyzed. Also the separation tests of hulls for recovery rate were conducted. The test results of the vol-oxidizer are going to be applied for operability. A study on the characteristics of the volatile gas produced during a vol-oxidation process is not included in this study

  5. A rapid enzymatic assay for high-throughput screening of adenosine-producing strains

    Science.gov (United States)

    Dong, Huina; Zu, Xin; Zheng, Ping; Zhang, Dawei

    2015-01-01

    Adenosine is a major local regulator of tissue function and industrially useful as precursor for the production of medicinal nucleoside substances. High-throughput screening of adenosine overproducers is important for industrial microorganism breeding. An enzymatic assay of adenosine was developed by combined adenosine deaminase (ADA) with indophenol method. The ADA catalyzes the cleavage of adenosine to inosine and NH3, the latter can be accurately determined by indophenol method. The assay system was optimized to deliver a good performance and could tolerate the addition of inorganic salts and many nutrition components to the assay mixtures. Adenosine could be accurately determined by this assay using 96-well microplates. Spike and recovery tests showed that this assay can accurately and reproducibly determine increases in adenosine in fermentation broth without any pretreatment to remove proteins and potentially interfering low-molecular-weight molecules. This assay was also applied to high-throughput screening for high adenosine-producing strains. The high selectivity and accuracy of the ADA assay provides rapid and high-throughput analysis of adenosine in large numbers of samples. PMID:25580842

  6. Machine learning in computational biology to accelerate high-throughput protein expression.

    Science.gov (United States)

    Sastry, Anand; Monk, Jonathan; Tegel, Hanna; Uhlen, Mathias; Palsson, Bernhard O; Rockberg, Johan; Brunk, Elizabeth

    2017-08-15

    The Human Protein Atlas (HPA) enables the simultaneous characterization of thousands of proteins across various tissues to pinpoint their spatial location in the human body. This has been achieved through transcriptomics and high-throughput immunohistochemistry-based approaches, where over 40 000 unique human protein fragments have been expressed in E. coli. These datasets enable quantitative tracking of entire cellular proteomes and present new avenues for understanding molecular-level properties influencing expression and solubility. Combining computational biology and machine learning identifies protein properties that hinder the HPA high-throughput antibody production pipeline. We predict protein expression and solubility with accuracies of 70% and 80%, respectively, based on a subset of key properties (aromaticity, hydropathy and isoelectric point). We guide the selection of protein fragments based on these characteristics to optimize high-throughput experimentation. We present the machine learning workflow as a series of IPython notebooks hosted on GitHub (https://github.com/SBRG/Protein_ML). The workflow can be used as a template for analysis of further expression and solubility datasets. ebrunk@ucsd.edu or johanr@biotech.kth.se. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  7. A priori Considerations When Conducting High-Throughput Amplicon-Based Sequence Analysis

    Directory of Open Access Journals (Sweden)

    Aditi Sengupta

    2016-03-01

    Full Text Available Amplicon-based sequencing strategies that include 16S rRNA and functional genes, alongside “meta-omics” analyses of communities of microorganisms, have allowed researchers to pose questions and find answers to “who” is present in the environment and “what” they are doing. Next-generation sequencing approaches that aid microbial ecology studies of agricultural systems are fast gaining popularity among agronomy, crop, soil, and environmental science researchers. Given the rapid development of these high-throughput sequencing techniques, researchers with no prior experience will desire information about the best practices that can be used before actually starting high-throughput amplicon-based sequence analyses. We have outlined items that need to be carefully considered in experimental design, sampling, basic bioinformatics, sequencing of mock communities and negative controls, acquisition of metadata, and in standardization of reaction conditions as per experimental requirements. Not all considerations mentioned here may pertain to a particular study. The overall goal is to inform researchers about considerations that must be taken into account when conducting high-throughput microbial DNA sequencing and sequences analysis.

  8. High-throughput purification of recombinant proteins using self-cleaving intein tags.

    Science.gov (United States)

    Coolbaugh, M J; Shakalli Tang, M J; Wood, D W

    2017-01-01

    High throughput methods for recombinant protein production using E. coli typically involve the use of affinity tags for simple purification of the protein of interest. One drawback of these techniques is the occasional need for tag removal before study, which can be hard to predict. In this work, we demonstrate two high throughput purification methods for untagged protein targets based on simple and cost-effective self-cleaving intein tags. Two model proteins, E. coli beta-galactosidase (βGal) and superfolder green fluorescent protein (sfGFP), were purified using self-cleaving versions of the conventional chitin-binding domain (CBD) affinity tag and the nonchromatographic elastin-like-polypeptide (ELP) precipitation tag in a 96-well filter plate format. Initial tests with shake flask cultures confirmed that the intein purification scheme could be scaled down, with >90% pure product generated in a single step using both methods. The scheme was then validated in a high throughput expression platform using 24-well plate cultures followed by purification in 96-well plates. For both tags and with both target proteins, the purified product was consistently obtained in a single-step, with low well-to-well and plate-to-plate variability. This simple method thus allows the reproducible production of highly pure untagged recombinant proteins in a convenient microtiter plate format. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Infra-red thermography for high throughput field phenotyping in Solanum tuberosum.

    Directory of Open Access Journals (Sweden)

    Ankush Prashar

    Full Text Available The rapid development of genomic technology has made high throughput genotyping widely accessible but the associated high throughput phenotyping is now the major limiting factor in genetic analysis of traits. This paper evaluates the use of thermal imaging for the high throughput field phenotyping of Solanum tuberosum for differences in stomatal behaviour. A large multi-replicated trial of a potato mapping population was used to investigate the consistency in genotypic rankings across different trials and across measurements made at different times of day and on different days. The results confirmed a high degree of consistency between the genotypic rankings based on relative canopy temperature on different occasions. Genotype discrimination was enhanced both through normalising data by expressing genotype temperatures as differences from image means and through the enhanced replication obtained by using overlapping images. A Monte Carlo simulation approach was used to confirm the magnitude of genotypic differences that it is possible to discriminate. The results showed a clear negative association between canopy temperature and final tuber yield for this population, when grown under ample moisture supply. We have therefore established infrared thermography as an easy, rapid and non-destructive screening method for evaluating large population trials for genetic analysis. We also envisage this approach as having great potential for evaluating plant response to stress under field conditions.

  10. Meta-Analysis of High-Throughput Datasets Reveals Cellular Responses Following Hemorrhagic Fever Virus Infection

    Directory of Open Access Journals (Sweden)

    Gavin C. Bowick

    2011-05-01

    Full Text Available The continuing use of high-throughput assays to investigate cellular responses to infection is providing a large repository of information. Due to the large number of differentially expressed transcripts, often running into the thousands, the majority of these data have not been thoroughly investigated. Advances in techniques for the downstream analysis of high-throughput datasets are providing additional methods for the generation of additional hypotheses for further investigation. The large number of experimental observations, combined with databases that correlate particular genes and proteins with canonical pathways, functions and diseases, allows for the bioinformatic exploration of functional networks that may be implicated in replication or pathogenesis. Herein, we provide an example of how analysis of published high-throughput datasets of cellular responses to hemorrhagic fever virus infection can generate additional functional data. We describe enrichment of genes involved in metabolism, post-translational modification and cardiac damage; potential roles for specific transcription factors and a conserved involvement of a pathway based around cyclooxygenase-2. We believe that these types of analyses can provide virologists with additional hypotheses for continued investigation.

  11. Image Harvest: an open-source platform for high-throughput plant image processing and analysis.

    Science.gov (United States)

    Knecht, Avi C; Campbell, Malachy T; Caprez, Adam; Swanson, David R; Walia, Harkamal

    2016-05-01

    High-throughput plant phenotyping is an effective approach to bridge the genotype-to-phenotype gap in crops. Phenomics experiments typically result in large-scale image datasets, which are not amenable for processing on desktop computers, thus creating a bottleneck in the image-analysis pipeline. Here, we present an open-source, flexible image-analysis framework, called Image Harvest (IH), for processing images originating from high-throughput plant phenotyping platforms. Image Harvest is developed to perform parallel processing on computing grids and provides an integrated feature for metadata extraction from large-scale file organization. Moreover, the integration of IH with the Open Science Grid provides academic researchers with the computational resources required for processing large image datasets at no cost. Image Harvest also offers functionalities to extract digital traits from images to interpret plant architecture-related characteristics. To demonstrate the applications of these digital traits, a rice (Oryza sativa) diversity panel was phenotyped and genome-wide association mapping was performed using digital traits that are used to describe different plant ideotypes. Three major quantitative trait loci were identified on rice chromosomes 4 and 6, which co-localize with quantitative trait loci known to regulate agronomically important traits in rice. Image Harvest is an open-source software for high-throughput image processing that requires a minimal learning curve for plant biologists to analyzephenomics datasets. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  12. Optical tools for high-throughput screening of abrasion resistance of combinatorial libraries of organic coatings

    Science.gov (United States)

    Potyrailo, Radislav A.; Chisholm, Bret J.; Olson, Daniel R.; Brennan, Michael J.; Molaison, Chris A.

    2002-02-01

    Design, validation, and implementation of an optical spectroscopic system for high-throughput analysis of combinatorially developed protective organic coatings are reported. Our approach replaces labor-intensive coating evaluation steps with an automated system that rapidly analyzes 8x6 arrays of coating elements that are deposited on a plastic substrate. Each coating element of the library is 10 mm in diameter and 2 to 5 micrometers thick. Performance of coatings is evaluated with respect to their resistance to wear abrasion because this parameter is one of the primary considerations in end-use applications. Upon testing, the organic coatings undergo changes that are impossible to quantitatively predict using existing knowledge. Coatings are abraded using industry-accepted abrasion test methods at single-or multiple-abrasion conditions, followed by high- throughput analysis of abrasion-induced light scatter. The developed automated system is optimized for the analysis of diffusively scattered light that corresponds to 0 to 30% haze. System precision of 0.1 to 2.5% relative standard deviation provides capability for the reliable ranking of coatings performance. While the system was implemented for high-throughput screening of combinatorially developed organic protective coatings for automotive applications, it can be applied to a variety of other applications where materials ranking can be achieved using optical spectroscopic tools.

  13. Assessing Morphological and Physiological Properties of Forest Species Using High Throughput Plant Phenotyping and Imaging Techniques

    Science.gov (United States)

    Mazis, A.; Hiller, J.; Morgan, P.; Awada, T.; Stoerger, V.

    2017-12-01

    High throughput plant phenotyping is increasingly being used to assess morphological and biophysical traits of economically important crops in agriculture. In this study, the potential application of this technique in natural resources management, through the characterization of woody plants regeneration, establishment, growth, and responses to water and nutrient manipulations was assessed. Two woody species were selected for this study, Quercus prinoides and Quercus bicolor. Seeds were collected from trees growing at the edge of their natural distribution in Nebraska and Missouri, USA. Seeds were germinated in the greenhouse and transferred to the Nebraska Innovation Campus Lemnatec3D High Throughput facility at the University of Nebraska-Lincoln. Seedlings subjected to water and N manipulations, were imaged twice or three times a week using four cameras (Visible, Fluorescence, Infrared and Hyperspectral), throughout the growing season. Traditional leaf to plant levels ecophysiological measurements were concurrently acquired to assess the relationship between these two techniques. These include gas exchange (LI 6400 and LI 6800, LICOR Inc., Lincoln NE), chlorophyll content, optical characteristics (Ocean Optics USB200), water and osmotic potentials, leaf area and weight and carbon isotope ratio. In the presentation, we highlight results on the potential use of high throughput plant phenotyping techniques to assess the morphology and physiology of woody species including responses to water availability and nutrient manipulation, and its broader application under field conditions and natural resources management. Also, we explore the different capabilities imaging provides us for modeling the plant physiological and morphological growth and how it can complement the current techniques

  14. High-Throughput Cloning and Expression Library Creation for Functional Proteomics

    Science.gov (United States)

    Festa, Fernanda; Steel, Jason; Bian, Xiaofang; Labaer, Joshua

    2013-01-01

    The study of protein function usually requires the use of a cloned version of the gene for protein expression and functional assays. This strategy is particular important when the information available regarding function is limited. The functional characterization of the thousands of newly identified proteins revealed by genomics requires faster methods than traditional single gene experiments, creating the need for fast, flexible and reliable cloning systems. These collections of open reading frame (ORF) clones can be coupled with high-throughput proteomics platforms, such as protein microarrays and cell-based assays, to answer biological questions. In this tutorial we provide the background for DNA cloning, discuss the major high-throughput cloning systems (Gateway® Technology, Flexi® Vector Systems, and Creator™ DNA Cloning System) and compare them side-by-side. We also report an example of high-throughput cloning study and its application in functional proteomics. This Tutorial is part of the International Proteomics Tutorial Programme (IPTP12). Details can be found at http://www.proteomicstutorials.org. PMID:23457047

  15. PCR cycles above routine numbers do not compromise high-throughput DNA barcoding results.

    Science.gov (United States)

    Vierna, J; Doña, J; Vizcaíno, A; Serrano, D; Jovani, R

    2017-10-01

    High-throughput DNA barcoding has become essential in ecology and evolution, but some technical questions still remain. Increasing the number of PCR cycles above the routine 20-30 cycles is a common practice when working with old-type specimens, which provide little amounts of DNA, or when facing annealing issues with the primers. However, increasing the number of cycles can raise the number of artificial mutations due to polymerase errors. In this work, we sequenced 20 COI libraries in the Illumina MiSeq platform. Libraries were prepared with 40, 45, 50, 55, and 60 PCR cycles from four individuals belonging to four species of four genera of cephalopods. We found no relationship between the number of PCR cycles and the number of mutations despite using a nonproofreading polymerase. Moreover, even when using a high number of PCR cycles, the resulting number of mutations was low enough not to be an issue in the context of high-throughput DNA barcoding (but may still remain an issue in DNA metabarcoding due to chimera formation). We conclude that the common practice of increasing the number of PCR cycles should not negatively impact the outcome of a high-throughput DNA barcoding study in terms of the occurrence of point mutations.

  16. A high throughput array microscope for the mechanical characterization of biomaterials

    Science.gov (United States)

    Cribb, Jeremy; Osborne, Lukas D.; Hsiao, Joe Ping-Lin; Vicci, Leandra; Meshram, Alok; O'Brien, E. Tim; Spero, Richard Chasen; Taylor, Russell; Superfine, Richard

    2015-02-01

    In the last decade, the emergence of high throughput screening has enabled the development of novel drug therapies and elucidated many complex cellular processes. Concurrently, the mechanobiology community has developed tools and methods to show that the dysregulation of biophysical properties and the biochemical mechanisms controlling those properties contribute significantly to many human diseases. Despite these advances, a complete understanding of the connection between biomechanics and disease will require advances in instrumentation that enable parallelized, high throughput assays capable of probing complex signaling pathways, studying biology in physiologically relevant conditions, and capturing specimen and mechanical heterogeneity. Traditional biophysical instruments are unable to meet this need. To address the challenge of large-scale, parallelized biophysical measurements, we have developed an automated array high-throughput microscope system that utilizes passive microbead diffusion to characterize mechanical properties of biomaterials. The instrument is capable of acquiring data on twelve-channels simultaneously, where each channel in the system can independently drive two-channel fluorescence imaging at up to 50 frames per second. We employ this system to measure the concentration-dependent apparent viscosity of hyaluronan, an essential polymer found in connective tissue and whose expression has been implicated in cancer progression.

  17. Image Harvest: an open-source platform for high-throughput plant image processing and analysis

    Science.gov (United States)

    Knecht, Avi C.; Campbell, Malachy T.; Caprez, Adam; Swanson, David R.; Walia, Harkamal

    2016-01-01

    High-throughput plant phenotyping is an effective approach to bridge the genotype-to-phenotype gap in crops. Phenomics experiments typically result in large-scale image datasets, which are not amenable for processing on desktop computers, thus creating a bottleneck in the image-analysis pipeline. Here, we present an open-source, flexible image-analysis framework, called Image Harvest (IH), for processing images originating from high-throughput plant phenotyping platforms. Image Harvest is developed to perform parallel processing on computing grids and provides an integrated feature for metadata extraction from large-scale file organization. Moreover, the integration of IH with the Open Science Grid provides academic researchers with the computational resources required for processing large image datasets at no cost. Image Harvest also offers functionalities to extract digital traits from images to interpret plant architecture-related characteristics. To demonstrate the applications of these digital traits, a rice (Oryza sativa) diversity panel was phenotyped and genome-wide association mapping was performed using digital traits that are used to describe different plant ideotypes. Three major quantitative trait loci were identified on rice chromosomes 4 and 6, which co-localize with quantitative trait loci known to regulate agronomically important traits in rice. Image Harvest is an open-source software for high-throughput image processing that requires a minimal learning curve for plant biologists to analyzephenomics datasets. PMID:27141917

  18. High-throughput gene expression profiling of memory differentiation in primary human T cells

    Directory of Open Access Journals (Sweden)

    Russell Kate

    2008-08-01

    Full Text Available Abstract Background The differentiation of naive T and B cells into memory lymphocytes is essential for immunity to pathogens. Therapeutic manipulation of this cellular differentiation program could improve vaccine efficacy and the in vitro expansion of memory cells. However, chemical screens to identify compounds that induce memory differentiation have been limited by 1 the lack of reporter-gene or functional assays that can distinguish naive and memory-phenotype T cells at high throughput and 2 a suitable cell-line representative of naive T cells. Results Here, we describe a method for gene-expression based screening that allows primary naive and memory-phenotype lymphocytes to be discriminated based on complex genes signatures corresponding to these differentiation states. We used ligation-mediated amplification and a fluorescent, bead-based detection system to quantify simultaneously 55 transcripts representing naive and memory-phenotype signatures in purified populations of human T cells. The use of a multi-gene panel allowed better resolution than any constituent single gene. The method was precise, correlated well with Affymetrix microarray data, and could be easily scaled up for high-throughput. Conclusion This method provides a generic solution for high-throughput differentiation screens in primary human T cells where no single-gene or functional assay is available. This screening platform will allow the identification of small molecules, genes or soluble factors that direct memory differentiation in naive human lymphocytes.

  19. CrossCheck: an open-source web tool for high-throughput screen data analysis.

    Science.gov (United States)

    Najafov, Jamil; Najafov, Ayaz

    2017-07-19

    Modern high-throughput screening methods allow researchers to generate large datasets that potentially contain important biological information. However, oftentimes, picking relevant hits from such screens and generating testable hypotheses requires training in bioinformatics and the skills to efficiently perform database mining. There are currently no tools available to general public that allow users to cross-reference their screen datasets with published screen datasets. To this end, we developed CrossCheck, an online platform for high-throughput screen data analysis. CrossCheck is a centralized database that allows effortless comparison of the user-entered list of gene symbols with 16,231 published datasets. These datasets include published data from genome-wide RNAi and CRISPR screens, interactome proteomics and phosphoproteomics screens, cancer mutation databases, low-throughput studies of major cell signaling mediators, such as kinases, E3 ubiquitin ligases and phosphatases, and gene ontological information. Moreover, CrossCheck includes a novel database of predicted protein kinase substrates, which was developed using proteome-wide consensus motif searches. CrossCheck dramatically simplifies high-throughput screen data analysis and enables researchers to dig deep into the published literature and streamline data-driven hypothesis generation. CrossCheck is freely accessible as a web-based application at http://proteinguru.com/crosscheck.

  20. Theory and implementation of a very high throughput true random number generator in field programmable gate array

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yonggang, E-mail: wangyg@ustc.edu.cn; Hui, Cong; Liu, Chong; Xu, Chao [Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China)

    2016-04-15

    The contribution of this paper is proposing a new entropy extraction mechanism based on sampling phase jitter in ring oscillators to make a high throughput true random number generator in a field programmable gate array (FPGA) practical. Starting from experimental observation and analysis of the entropy source in FPGA, a multi-phase sampling method is exploited to harvest the clock jitter with a maximum entropy and fast sampling speed. This parametrized design is implemented in a Xilinx Artix-7 FPGA, where the carry chains in the FPGA are explored to realize the precise phase shifting. The generator circuit is simple and resource-saving, so that multiple generation channels can run in parallel to scale the output throughput for specific applications. The prototype integrates 64 circuit units in the FPGA to provide a total output throughput of 7.68 Gbps, which meets the requirement of current high-speed quantum key distribution systems. The randomness evaluation, as well as its robustness to ambient temperature, confirms that the new method in a purely digital fashion can provide high-speed high-quality random bit sequences for a variety of embedded applications.

  1. Laboratory study of nitrate photolysis in Antarctic snow. I. Observed quantum yield, domain of photolysis, and secondary chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Meusinger, Carl; Johnson, Matthew S. [Department of Chemistry, University of Copenhagen, Copenhagen (Denmark); Berhanu, Tesfaye A.; Erbland, Joseph; Savarino, Joel, E-mail: jsavarino@lgge.obs.ujf-grenoble.fr [Univ. Grenoble Alpes, LGGE, F-38000 Grenoble (France); CNRS, LGGE, F-38000 Grenoble (France)

    2014-06-28

    Post-depositional processes alter nitrate concentration and nitrate isotopic composition in the top layers of snow at sites with low snow accumulation rates, such as Dome C, Antarctica. Available nitrate ice core records can provide input for studying past atmospheres and climate if such processes are understood. It has been shown that photolysis of nitrate in the snowpack plays a major role in nitrate loss and that the photolysis products have a significant influence on the local troposphere as well as on other species in the snow. Reported quantum yields for the main reaction spans orders of magnitude – apparently a result of whether nitrate is located at the air-ice interface or in the ice matrix – constituting the largest uncertainty in models of snowpack NO{sub x} emissions. Here, a laboratory study is presented that uses snow from Dome C and minimizes effects of desorption and recombination by flushing the snow during irradiation with UV light. A selection of UV filters allowed examination of the effects of the 200 and 305 nm absorption bands of nitrate. Nitrate concentration and photon flux were measured in the snow. The quantum yield for loss of nitrate was observed to decrease from 0.44 to 0.003 within what corresponds to days of UV exposure in Antarctica. The superposition of photolysis in two photochemical domains of nitrate in snow is proposed: one of photolabile nitrate, and one of buried nitrate. The difference lies in the ability of reaction products to escape the snow crystal, versus undergoing secondary (recombination) chemistry. Modeled NO{sub x} emissions may increase significantly above measured values due to the observed quantum yield in this study. The apparent quantum yield in the 200 nm band was found to be ∼1%, much lower than reported for aqueous chemistry. A companion paper presents an analysis of the change in isotopic composition of snowpack nitrate based on the same samples as in this study.

  2. Optimizing transformations for automated, high throughput analysis of flow cytometry data.

    Science.gov (United States)

    Finak, Greg; Perez, Juan-Manuel; Weng, Andrew; Gottardo, Raphael

    2010-11-04

    In a high throughput setting, effective flow cytometry data analysis depends heavily on proper data preprocessing. While usual preprocessing steps of quality assessment, outlier removal, normalization, and gating have received considerable scrutiny from the community, the influence of data transformation on the output of high throughput analysis has been largely overlooked. Flow cytometry measurements can vary over several orders of magnitude, cell populations can have variances that depend on their mean fluorescence intensities, and may exhibit heavily-skewed distributions. Consequently, the choice of data transformation can influence the output of automated gating. An appropriate data transformation aids in data visualization and gating of cell populations across the range of data. Experience shows that the choice of transformation is data specific. Our goal here is to compare the performance of different transformations applied to flow cytometry data in the context of automated gating in a high throughput, fully automated setting. We examine the most common transformations used in flow cytometry, including the generalized hyperbolic arcsine, biexponential, linlog, and generalized Box-Cox, all within the BioConductor flowCore framework that is widely used in high throughput, automated flow cytometry data analysis. All of these transformations have adjustable parameters whose effects upon the data are non-intuitive for most users. By making some modelling assumptions about the transformed data, we develop maximum likelihood criteria to optimize parameter choice for these different transformations. We compare the performance of parameter-optimized and default-parameter (in flowCore) data transformations on real and simulated data by measuring the variation in the locations of cell populations across samples, discovered via automated gating in both the scatter and fluorescence channels. We find that parameter-optimized transformations improve visualization, reduce

  3. Optimizing transformations for automated, high throughput analysis of flow cytometry data

    Directory of Open Access Journals (Sweden)

    Weng Andrew

    2010-11-01

    Full Text Available Abstract Background In a high throughput setting, effective flow cytometry data analysis depends heavily on proper data preprocessing. While usual preprocessing steps of quality assessment, outlier removal, normalization, and gating have received considerable scrutiny from the community, the influence of data transformation on the output of high throughput analysis has been largely overlooked. Flow cytometry measurements can vary over several orders of magnitude, cell populations can have variances that depend on their mean fluorescence intensities, and may exhibit heavily-skewed distributions. Consequently, the choice of data transformation can influence the output of automated gating. An appropriate data transformation aids in data visualization and gating of cell populations across the range of data. Experience shows that the choice of transformation is data specific. Our goal here is to compare the performance of different transformations applied to flow cytometry data in the context of automated gating in a high throughput, fully automated setting. We examine the most common transformations used in flow cytometry, including the generalized hyperbolic arcsine, biexponential, linlog, and generalized Box-Cox, all within the BioConductor flowCore framework that is widely used in high throughput, automated flow cytometry data analysis. All of these transformations have adjustable parameters whose effects upon the data are non-intuitive for most users. By making some modelling assumptions about the transformed data, we develop maximum likelihood criteria to optimize parameter choice for these different transformations. Results We compare the performance of parameter-optimized and default-parameter (in flowCore data transformations on real and simulated data by measuring the variation in the locations of cell populations across samples, discovered via automated gating in both the scatter and fluorescence channels. We find that parameter

  4. A cell-based high-throughput screening assay for radiation susceptibility using automated cell counting

    International Nuclear Information System (INIS)

    Hodzic, Jasmina; Dingjan, Ilse; Maas, Mariëlle JP; Meulen-Muileman, Ida H van der; Menezes, Renee X de; Heukelom, Stan; Verheij, Marcel; Gerritsen, Winald R; Geldof, Albert A; Triest, Baukelien van; Beusechem, Victor W van

    2015-01-01

    Radiotherapy is one of the mainstays in the treatment for cancer, but its success can be limited due to inherent or acquired resistance. Mechanisms underlying radioresistance in various cancers are poorly understood and available radiosensitizers have shown only modest clinical benefit. There is thus a need to identify new targets and drugs for more effective sensitization of cancer cells to irradiation. Compound and RNA interference high-throughput screening technologies allow comprehensive enterprises to identify new agents and targets for radiosensitization. However, the gold standard assay to investigate radiosensitivity of cancer cells in vitro, the colony formation assay (CFA), is unsuitable for high-throughput screening. We developed a new high-throughput screening method for determining radiation susceptibility. Fast and uniform irradiation of batches up to 30 microplates was achieved using a Perspex container and a clinically employed linear accelerator. The readout was done by automated counting of fluorescently stained nuclei using the Acumen eX3 laser scanning cytometer. Assay performance was compared to that of the CFA and the CellTiter-Blue homogeneous uniform-well cell viability assay. The assay was validated in a whole-genome siRNA library screening setting using PC-3 prostate cancer cells. On 4 different cancer cell lines, the automated cell counting assay produced radiation dose response curves that followed a linear-quadratic equation and that exhibited a better correlation to the results of the CFA than did the cell viability assay. Moreover, the cell counting assay could be used to detect radiosensitization by silencing DNA-PKcs or by adding caffeine. In a high-throughput screening setting, using 4 Gy irradiated and control PC-3 cells, the effects of DNA-PKcs siRNA and non-targeting control siRNA could be clearly discriminated. We developed a simple assay for radiation susceptibility that can be used for high-throughput screening. This will aid

  5. High-throughput droplet analysis and multiplex DNA detection in the microfluidic platform equipped with a robust sample-introduction technique

    International Nuclear Information System (INIS)

    Chen, Jinyang; Ji, Xinghu; He, Zhike

    2015-01-01

    In this work, a simple, flexible and low-cost sample-introduction technique was developed and integrated with droplet platform. The sample-introduction strategy was realized based on connecting the components of positive pressure input device, sample container and microfluidic chip through the tygon tubing with homemade polydimethylsiloxane (PDMS) adaptor, so the sample was delivered into the microchip from the sample container under the driving of positive pressure. This sample-introduction technique is so robust and compatible that could be integrated with T-junction, flow-focus or valve-assisted droplet microchips. By choosing the PDMS adaptor with proper dimension, the microchip could be flexibly equipped with various types of familiar sample containers, makes the sampling more straightforward without trivial sample transfer or loading. And the convenient sample changing was easily achieved by positioning the adaptor from one sample container to another. Benefiting from the proposed technique, the time-dependent concentration gradient was generated and applied for quantum dot (QD)-based fluorescence barcoding within droplet chip. High-throughput droplet screening was preliminarily demonstrated through the investigation of the quenching efficiency of ruthenium complex to the fluorescence of QD. More importantly, multiplex DNA assay was successfully carried out in the integrated system, which shows the practicability and potentials in high-throughput biosensing. - Highlights: • A simple, robust and low-cost sample-introduction technique was developed. • Convenient and flexible sample changing was achieved in microfluidic system. • Novel strategy of concentration gradient generation was presented for barcoding. • High-throughput droplet screening could be realized in the integrated platform. • Multiplex DNA assay was successfully carried out in the droplet platform

  6. High-throughput droplet analysis and multiplex DNA detection in the microfluidic platform equipped with a robust sample-introduction technique

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jinyang; Ji, Xinghu [Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); He, Zhike, E-mail: zhkhe@whu.edu.cn [Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Suzhou Institute of Wuhan University, Suzhou 215123 (China)

    2015-08-12

    In this work, a simple, flexible and low-cost sample-introduction technique was developed and integrated with droplet platform. The sample-introduction strategy was realized based on connecting the components of positive pressure input device, sample container and microfluidic chip through the tygon tubing with homemade polydimethylsiloxane (PDMS) adaptor, so the sample was delivered into the microchip from the sample container under the driving of positive pressure. This sample-introduction technique is so robust and compatible that could be integrated with T-junction, flow-focus or valve-assisted droplet microchips. By choosing the PDMS adaptor with proper dimension, the microchip could be flexibly equipped with various types of familiar sample containers, makes the sampling more straightforward without trivial sample transfer or loading. And the convenient sample changing was easily achieved by positioning the adaptor from one sample container to another. Benefiting from the proposed technique, the time-dependent concentration gradient was generated and applied for quantum dot (QD)-based fluorescence barcoding within droplet chip. High-throughput droplet screening was preliminarily demonstrated through the investigation of the quenching efficiency of ruthenium complex to the fluorescence of QD. More importantly, multiplex DNA assay was successfully carried out in the integrated system, which shows the practicability and potentials in high-throughput biosensing. - Highlights: • A simple, robust and low-cost sample-introduction technique was developed. • Convenient and flexible sample changing was achieved in microfluidic system. • Novel strategy of concentration gradient generation was presented for barcoding. • High-throughput droplet screening could be realized in the integrated platform. • Multiplex DNA assay was successfully carried out in the droplet platform.

  7. Relativistic quantum chemistry of the superheavy elements. Closed-shell element 114 as a case study

    International Nuclear Information System (INIS)

    Schwerdtfeger, Peter; Seth, Michael

    2002-01-01

    The chemistry of superheavy element 114 is reviewed. The ground state of element 114 is closed shell [112]7s 2 7p 1/2 2 and shows a distinct chemical inertness (low reactivity). This inertness makes it rather difficult to study the atom-at-a-time chemistry of 114 in the gas or liquid phase. (author)

  8. Fluorescent-magnetic dual-encoded nanospheres: a promising tool for fast-simultaneous-addressable high-throughput analysis

    Science.gov (United States)

    Xie, Min; Hu, Jun; Wen, Cong-Ying; Zhang, Zhi-Ling; Xie, Hai-Yan; Pang, Dai-Wen

    2012-01-01

    Bead-based optical encoding or magnetic encoding techniques are promising in high-throughput multiplexed detection and separation of numerous species under complicated conditions. Therefore, a self-assembly strategy implemented in an organic solvent is put forward to fabricate fluorescent-magnetic dual-encoded nanospheres. Briefly, hydrophobic trioctylphosphine oxide-capped CdSe/ZnS quantum dots (QDs) and oleic acid-capped nano-γ-Fe2O3 magnetic particles are directly, selectively and controllably assembled on branched poly(ethylene imine)-coated nanospheres without any pretreatment, which is crucial to keep the high quantum yield of QDs and good dispersibility of γ-Fe2O3. Owing to the tunability of coating amounts of QDs and γ-Fe2O3 as well as controllable fluorescent emissions of deposited-QDs, dual-encoded nanospheres with different photoluminescent emissions and gradient magnetic susceptibility are constructed. Using this improved layer-by-layer self-assembly approach, deposition of hydrophobic nanoparticles onto hydrophilic carriers in organic media can be easily realized; meanwhile, fluorescent-magnetic dual-functional nanospheres can be further equipped with readable optical and magnetic addresses. The resultant fluorescent-magnetic dual-encoded nanospheres possess both the unique optical properties of QDs and the superparamagnetic properties of γ-Fe2O3, exhibiting good monodispersibility, huge encoding capacity and nanoscale particle size. Compared with the encoded microbeads reported by others, the nanometre scale of the dual-encoded nanospheres gives them minimum steric hindrance and higher flexibility.

  9. On the measurements of molecular similarity: a connection between quantum chemistry and artificial intelligence

    International Nuclear Information System (INIS)

    Carbo, R.; Calabuig, B.

    1988-01-01

    Molecular similarity measures within the quantum concept of density functions are described and analyzed. It is intended to show how artificial intelligence techniques can be used within the framework of quantum theory, in order to study and classify the molecular structures and their properties. (A.C.A.S) [pt

  10. Quantum chemistry and dynamics of the abstraction reaction of H atoms from formaldehyde

    Energy Technology Data Exchange (ETDEWEB)

    Siaï, A. [Faculté des Sciences de Tunis, Département de Physique, (LPMC), Université de Tunis El Manar, 2092 Tunis (Tunisia); Oueslati, I. [Faculté des Sciences de Tunis, Département de Physique, (LPMC), Université de Tunis El Manar, 2092 Tunis (Tunisia); Observatoire de Paris-Meudon, Sorbonne Universités, UPMC Univ Paris 06, UMR8112 du CNRS, LERMA, 5 Place Jules Janssen, 92195 Meudon cedex (France); Académie Militaire, Fondouk Jedid, 8012 Nabeul (Tunisia); Kerkeni, Boutheïna, E-mail: Boutheina.kerkeni@obspm.fr [Faculté des Sciences de Tunis, Département de Physique, (LPMC), Université de Tunis El Manar, 2092 Tunis (Tunisia); Observatoire de Paris-Meudon, Sorbonne Universités, UPMC Univ Paris 06, UMR8112 du CNRS, LERMA, 5 Place Jules Janssen, 92195 Meudon cedex (France); Institut Supérieur des Arts Multimédia de la Manouba, Université de la Manouba, 2010 la Manouba (Tunisia)

    2016-08-02

    This work reports a reduced dimensionality rate constant calculation of the H-abstraction reaction from formaldehyde. Quantum scattering calculations are performed treating explicitly the bonds being broken and formed. Geometry optimisations and frequency calculations are done at the MP2/cc-pVTZ level while energies are calculated with the CCSD(T) method. An analytical potential energy surface was developed from a relatively small number of grid points. When compared to semi-classical approaches, the quantum scattering calculations show that quantum tunnelling yields large contributions at low temperatures. At 200 K, we note a difference of about 5 orders of magnitude between transition state theory (TST) and quantum rate constants. Our predicted results show that the quantum and the CVT/SCT rate constants are in reasonable agreement with the available experiment at high temperatures, but that the last one gives better agreement to experimental results at low temperatures.

  11. Quantum Chemistry on Quantum Computers: A Polynomial-Time Quantum Algorithm for Constructing the Wave Functions of Open-Shell Molecules.

    Science.gov (United States)

    Sugisaki, Kenji; Yamamoto, Satoru; Nakazawa, Shigeaki; Toyota, Kazuo; Sato, Kazunobu; Shiomi, Daisuke; Takui, Takeji

    2016-08-18

    Quantum computers are capable to efficiently perform full configuration interaction (FCI) calculations of atoms and molecules by using the quantum phase estimation (QPE) algorithm. Because the success probability of the QPE depends on the overlap between approximate and exact wave functions, efficient methods to prepare accurate initial guess wave functions enough to have sufficiently large overlap with the exact ones are highly desired. Here, we propose a quantum algorithm to construct the wave function consisting of one configuration state function, which is suitable for the initial guess wave function in QPE-based FCI calculations of open-shell molecules, based on the addition theorem of angular momentum. The proposed quantum algorithm enables us to prepare the wave function consisting of an exponential number of Slater determinants only by a polynomial number of quantum operations.

  12. Effects of quantum chemistry models for bound electrons on positron annihilation spectra for atoms and small molecules

    International Nuclear Information System (INIS)

    Wang Feng; Ma Xiaoguang; Selvam, Lalitha; Gribakin, Gleb; Surko, Clifford M

    2012-01-01

    The Doppler-shift spectra of the γ-rays from positron annihilation in molecules were determined by using the momentum distribution of the annihilation electron–positron pair. The effect of the positron wavefunction on spectra was analysed in a recent paper (Green et al 2012 New J. Phys. 14 035021). In this companion paper, we focus on the dominant contribution to the spectra, which arises from the momenta of the bound electrons. In particular, we use computational quantum chemistry models (Hartree–Fock with two basis sets and density functional theory (DFT)) to calculate the wavefunctions of the bound electrons. Numerical results are presented for noble gases and small molecules such as H 2 , N 2 , O 2 , CH 4 and CF 4 . The calculations reveal relatively small effects on the Doppler-shift spectra from the level of inclusion of electron correlation energy in the models. For atoms, the difference in the full-width at half-maximum of the spectra obtained using the Hartree–Fock and DFT models does not exceed 2%. For molecules the difference can be much larger, reaching 8% for some molecular orbitals. These results indicate that the predicted positron annihilation spectra for molecules are generally more sensitive to inclusion of electron correlation energies in the quantum chemistry model than the spectra for atoms are. (paper)

  13. Miniaturized Analytical Platforms From Nanoparticle Components: Studies in the Construction, Characterization, and High-Throughput Usage of These Novel Architectures

    Energy Technology Data Exchange (ETDEWEB)

    Pris, Andrew David [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    exhibiting a variety of surface chemistries and attempts to deconvolute general adsorption rules for their assembly on various substrates. Chapter 2 extends the usage of self-assembly of polymeric nanoparticles through a layer-by-layer deposition concept and photolithography methodologies to create analytical platforms with a vertical height controlled within the nanometer regime. This platform is then furthered in Chapter 3 by employing this integrated concept as a bio-recognition platform, with the extension of the method to a high-throughput screening system explored. Chapter 4 exploits two different types of nanoparticles, silica and gold, as multiplexed, self-assembled immunoassay sensors. This final research chapter is followed by a general summation and future prospectus section that concludes the dissertation.

  14. A High-Throughput Mass Spectrometry Assay Coupled with Redox Activity Testing Reduces Artifacts and False Positives in Lysine Demethylase Screening.

    Science.gov (United States)

    Wigle, Tim J; Swinger, Kerren K; Campbell, John E; Scholle, Michael D; Sherrill, John; Admirand, Elizabeth A; Boriack-Sjodin, P Ann; Kuntz, Kevin W; Chesworth, Richard; Moyer, Mikel P; Scott, Margaret Porter; Copeland, Robert A

    2015-07-01

    Demethylation of histones by lysine demethylases (KDMs) plays a critical role in controlling gene transcription. Aberrant demethylation may play a causal role in diseases such as cancer. Despite the biological significance of these enzymes, there are limited assay technologies for study of KDMs and few quality chemical probes available to interrogate their biology. In this report, we demonstrate the utility of self-assembled monolayer desorption/ionization (SAMDI) mass spectrometry for the investigation of quantitative KDM enzyme kinetics and for high-throughput screening for KDM inhibitors. SAMDI can be performed in 384-well format and rapidly allows reaction components to be purified prior to injection into a mass spectrometer, without a throughput-limiting liquid chromatography step. We developed sensitive and robust assays for KDM1A (LSD1, AOF2) and KDM4C (JMJD2C, GASC1) and screened 13,824 compounds against each enzyme. Hits were rapidly triaged using a redox assay to identify compounds that interfered with the catalytic oxidation chemistry used by the KDMs for the demethylation reaction. We find that overall this high-throughput mass spectrometry platform coupled with the elimination of redox active compounds leads to a hit rate that is manageable for follow-up work. © 2015 Society for Laboratory Automation and Screening.

  15. Building blocks for the development of an interface for high-throughput thin layer chromatography/ambient mass spectrometric analysis: a green methodology.

    Science.gov (United States)

    Cheng, Sy-Chyi; Huang, Min-Zong; Wu, Li-Chieh; Chou, Chih-Chiang; Cheng, Chu-Nian; Jhang, Siou-Sian; Shiea, Jentaie

    2012-07-17

    Interfacing thin layer chromatography (TLC) with ambient mass spectrometry (AMS) has been an important area of analytical chemistry because of its capability to rapidly separate and characterize the chemical compounds. In this study, we have developed a high-throughput TLC-AMS system using building blocks to deal, deliver, and collect the TLC plate through an electrospray-assisted laser desorption ionization (ELDI) source. This is the first demonstration of the use of building blocks to construct and test the TLC-MS interfacing system. With the advantages of being readily available, cheap, reusable, and extremely easy to modify without consuming any material or reagent, the use of building blocks to develop the TLC-AMS interface is undoubtedly a green methodology. The TLC plate delivery system consists of a storage box, plate dealing component, conveyer, light sensor, and plate collecting box. During a TLC-AMS analysis, the TLC plate was sent to the conveyer from a stack of TLC plates placed in the storage box. As the TLC plate passed through the ELDI source, the chemical compounds separated on the plate would be desorbed by laser desorption and subsequently postionized by electrospray ionization. The samples, including a mixture of synthetic dyes and extracts of pharmaceutical drugs, were analyzed to demonstrate the capability of this TLC-ELDI/MS system for high-throughput analysis.

  16. Role of Precursor-Conversion Chemistry in the Crystal-Phase Control of Catalytically Grown Colloidal Semiconductor Quantum Wires.

    Science.gov (United States)

    Wang, Fudong; Buhro, William E

    2017-12-26

    Crystal-phase control is one of the most challenging problems in nanowire growth. We demonstrate that, in the solution-phase catalyzed growth of colloidal cadmium telluride (CdTe) quantum wires (QWs), the crystal phase can be controlled by manipulating the reaction chemistry of the Cd precursors and tri-n-octylphosphine telluride (TOPTe) to favor the production of either a CdTe solute or Te, which consequently determines the composition and (liquid or solid) state of the Bi x Cd y Te z catalyst nanoparticles. Growth of single-phase (e.g., wurtzite) QWs is achieved only from solid catalysts (y ≪ z) that enable the solution-solid-solid growth of the QWs, whereas the liquid catalysts (y ≈ z) fulfill the solution-liquid-solid growth of the polytypic QWs. Factors that affect the precursor-conversion chemistry are systematically accounted for, which are correlated with a kinetic study of the composition and state of the catalyst nanoparticles to understand the mechanism. This work reveals the role of the precursor-reaction chemistry in the crystal-phase control of catalytically grown colloidal QWs, opening the possibility of growing phase-pure QWs of other compositions.

  17. Chlorophyll fluorescence is a rigorous, high throughput tool to analyze the impacts of genotype, species, and stress on plant and ecosystem productivity

    Science.gov (United States)

    Ewers, B. E.; Pleban, J. R.; Aston, T.; Beverly, D.; Speckman, H. N.; Hosseini, A.; Bretfeld, M.; Edwards, C.; Yarkhunova, Y.; Weinig, C.; Mackay, D. S.

    2017-12-01

    Abiotic and biotic stresses reduce plant productivity, yet high-throughput characterization of plant responses across genotypes, species and stress conditions are limited by both instrumentation and data analysis techniques. Recent developments in chlorophyll a fluorescence measurement at leaf to landscape scales could improve our predictive understanding of plants response to stressors. We analyzed the interaction of species and stress across two crop types, five gymnosperm and two angiosperm tree species from boreal and montane forests, grasses, forbs and shrubs from sagebrush steppe, and 30 tree species from seasonally wet tropical forest. We also analyzed chlorophyll fluorescence and gas exchange data from twelve Brassica rapa crop accessions and 120 recombinant inbred lines to investigate phenotypic responses to drought. These data represent more than 10,000 measurements of fluorescence and allow us to answer two questions 1) are the measurements from high-throughput, hand held and drone-mounted instruments quantitatively similar to lower throughput camera and gas exchange mounted instruments and 2) do the measurements find differences in genotypic, species and environmental stress on plants? We found through regression that the high and low throughput instruments agreed across both individual chlorophyll fluorescence components and calculated ratios and were not different from a 1:1 relationship with correlation greater than 0.9. We used hierarchical Bayesian modeling to test the second question. We found a linear relationship between the fluorescence-derived quantum yield of PSII and the quantum yield of CO2 assimilation from gas-exchange, with a slope of ca. 0.1 indicating that the efficiency of the entire photosynthetic process was about 10% of PSII across genotypes, species and drought stress. Posterior estimates of quantum yield revealed that drought-treatment, genotype and species differences were preserved when accounting for measurement uncertainty

  18. Novel high-throughput cell-based hybridoma screening methodology using the Celigo Image Cytometer.

    Science.gov (United States)

    Zhang, Haohai; Chan, Leo Li-Ying; Rice, William; Kassam, Nasim; Longhi, Maria Serena; Zhao, Haitao; Robson, Simon C; Gao, Wenda; Wu, Yan

    2017-08-01

    Hybridoma screening is a critical step for antibody discovery, which necessitates prompt identification of potential clones from hundreds to thousands of hybridoma cultures against the desired immunogen. Technical issues associated with ELISA- and flow cytometry-based screening limit accuracy and diminish high-throughput capability, increasing time and cost. Conventional ELISA screening with coated antigen is also impractical for difficult-to-express hydrophobic membrane antigens or multi-chain protein complexes. Here, we demonstrate novel high-throughput screening methodology employing the Celigo Image Cytometer, which avoids nonspecific signals by contrasting antibody binding signals directly on living cells, with and without recombinant antigen expression. The image cytometry-based high-throughput screening method was optimized by detecting the binding of hybridoma supernatants to the recombinant antigen CD39 expressed on Chinese hamster ovary (CHO) cells. Next, the sensitivity of the image cytometer was demonstrated by serial dilution of purified CD39 antibody. Celigo was used to measure antibody affinities of commercial and in-house antibodies to membrane-bound CD39. This cell-based screening procedure can be completely accomplished within one day, significantly improving throughput and efficiency of hybridoma screening. Furthermore, measuring direct antibody binding to living cells eliminated both false positive and false negative hits. The image cytometry method was highly sensitive and versatile, and could detect positive antibody in supernatants at concentrations as low as ~5ng/mL, with concurrent K d binding affinity coefficient determination. We propose that this screening method will greatly facilitate antibody discovery and screening technologies. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. A high-throughput, multi-channel photon-counting detector with picosecond timing

    Science.gov (United States)

    Lapington, J. S.; Fraser, G. W.; Miller, G. M.; Ashton, T. J. R.; Jarron, P.; Despeisse, M.; Powolny, F.; Howorth, J.; Milnes, J.

    2009-06-01

    High-throughput photon counting with high time resolution is a niche application area where vacuum tubes can still outperform solid-state devices. Applications in the life sciences utilizing time-resolved spectroscopies, particularly in the growing field of proteomics, will benefit greatly from performance enhancements in event timing and detector throughput. The HiContent project is a collaboration between the University of Leicester Space Research Centre, the Microelectronics Group at CERN, Photek Ltd., and end-users at the Gray Cancer Institute and the University of Manchester. The goal is to develop a detector system specifically designed for optical proteomics, capable of high content (multi-parametric) analysis at high throughput. The HiContent detector system is being developed to exploit this niche market. It combines multi-channel, high time resolution photon counting in a single miniaturized detector system with integrated electronics. The combination of enabling technologies; small pore microchannel plate devices with very high time resolution, and high-speed multi-channel ASIC electronics developed for the LHC at CERN, provides the necessary building blocks for a high-throughput detector system with up to 1024 parallel counting channels and 20 ps time resolution. We describe the detector and electronic design, discuss the current status of the HiContent project and present the results from a 64-channel prototype system. In the absence of an operational detector, we present measurements of the electronics performance using a pulse generator to simulate detector events. Event timing results from the NINO high-speed front-end ASIC captured using a fast digital oscilloscope are compared with data taken with the proposed electronic configuration which uses the multi-channel HPTDC timing ASIC.

  20. A high-throughput, multi-channel photon-counting detector with picosecond timing

    International Nuclear Information System (INIS)

    Lapington, J.S.; Fraser, G.W.; Miller, G.M.; Ashton, T.J.R.; Jarron, P.; Despeisse, M.; Powolny, F.; Howorth, J.; Milnes, J.

    2009-01-01

    High-throughput photon counting with high time resolution is a niche application area where vacuum tubes can still outperform solid-state devices. Applications in the life sciences utilizing time-resolved spectroscopies, particularly in the growing field of proteomics, will benefit greatly from performance enhancements in event timing and detector throughput. The HiContent project is a collaboration between the University of Leicester Space Research Centre, the Microelectronics Group at CERN, Photek Ltd., and end-users at the Gray Cancer Institute and the University of Manchester. The goal is to develop a detector system specifically designed for optical proteomics, capable of high content (multi-parametric) analysis at high throughput. The HiContent detector system is being developed to exploit this niche market. It combines multi-channel, high time resolution photon counting in a single miniaturized detector system with integrated electronics. The combination of enabling technologies; small pore microchannel plate devices with very high time resolution, and high-speed multi-channel ASIC electronics developed for the LHC at CERN, provides the necessary building blocks for a high-throughput detector system with up to 1024 parallel counting channels and 20 ps time resolution. We describe the detector and electronic design, discuss the current status of the HiContent project and present the results from a 64-channel prototype system. In the absence of an operational detector, we present measurements of the electronics performance using a pulse generator to simulate detector events. Event timing results from the NINO high-speed front-end ASIC captured using a fast digital oscilloscope are compared with data taken with the proposed electronic configuration which uses the multi-channel HPTDC timing ASIC.

  1. Engineering a vitamin B12 high-throughput screening system by riboswitch sensor in Sinorhizobium meliloti.

    Science.gov (United States)

    Cai, Yingying; Xia, Miaomiao; Dong, Huina; Qian, Yuan; Zhang, Tongcun; Zhu, Beiwei; Wu, Jinchuan; Zhang, Dawei

    2018-05-11

    As a very important coenzyme in the cell metabolism, Vitamin B 12 (cobalamin, VB 12 ) has been widely used in food and medicine fields. The complete biosynthesis of VB 12 requires approximately 30 genes, but overexpression of these genes did not result in expected increase of VB 12 production. High-yield VB 12 -producing strains are usually obtained by mutagenesis treatments, thus developing an efficient screening approach is urgently needed. By the help of engineered strains with varied capacities of VB 12 production, a riboswitch library was constructed and screened, and the btuB element from Salmonella typhimurium was identified as the best regulatory device. A flow cytometry high-throughput screening system was developed based on the btuB riboswitch with high efficiency to identify positive mutants. Mutation of Sinorhizobium meliloti (S. meliloti) was optimized using the novel mutation technique of atmospheric and room temperature plasma (ARTP). Finally, the mutant S. meliloti MC5-2 was obtained and considered as a candidate for industrial applications. After 7 d's cultivation on a rotary shaker at 30 °C, the VB 12 titer of S. meliloti MC5-2 reached 156 ± 4.2 mg/L, which was 21.9% higher than that of the wild type strain S. meliloti 320 (128 ± 3.2 mg/L). The genome of S. meliloti MC5-2 was sequenced, and gene mutations were identified and analyzed. To our knowledge, it is the first time that a riboswitch element was used in S. meliloti. The flow cytometry high-throughput screening system was successfully developed and a high-yield VB 12 producing strain was obtained. The identified and analyzed gene mutations gave useful information for developing high-yield strains by metabolic engineering. Overall, this work provides a useful high-throughput screening method for developing high VB 12 -yield strains.

  2. A high throughput architecture for a low complexity soft-output demapping algorithm

    Science.gov (United States)

    Ali, I.; Wasenmüller, U.; Wehn, N.

    2015-11-01

    Iterative channel decoders such as Turbo-Code and LDPC decoders show exceptional performance and therefore they are a part of many wireless communication receivers nowadays. These decoders require a soft input, i.e., the logarithmic likelihood ratio (LLR) of the received bits with a typical quantization of 4 to 6 bits. For computing the LLR values from a received complex symbol, a soft demapper is employed in the receiver. The implementation cost of traditional soft-output demapping methods is relatively large in high order modulation systems, and therefore low complexity demapping algorithms are indispensable in low power receivers. In the presence of multiple wireless communication standards where each standard defines multiple modulation schemes, there is a need to have an efficient demapper architecture covering all the flexibility requirements of these standards. Another challenge associated with hardware implementation of the demapper is to achieve a very high throughput in double iterative systems, for instance, MIMO and Code-Aided Synchronization. In this paper, we present a comprehensive communication and hardware performance evaluation of low complexity soft-output demapping algorithms to select the best algorithm for implementation. The main goal of this work is to design a high throughput, flexible, and area efficient architecture. We describe architectures to execute the investigated algorithms. We implement these architectures on a FPGA device to evaluate their hardware performance. The work has resulted in a hardware architecture based on the figured out best low complexity algorithm delivering a high throughput of 166 Msymbols/second for Gray mapped 16-QAM modulation on Virtex-5. This efficient architecture occupies only 127 slice registers, 248 slice LUTs and 2 DSP48Es.

  3. Genecentric: a package to uncover graph-theoretic structure in high-throughput epistasis data.

    Science.gov (United States)

    Gallant, Andrew; Leiserson, Mark D M; Kachalov, Maxim; Cowen, Lenore J; Hescott, Benjamin J

    2013-01-18

    New technology has resulted in high-throughput screens for pairwise genetic interactions in yeast and other model organisms. For each pair in a collection of non-essential genes, an epistasis score is obtained, representing how much sicker (or healthier) the double-knockout organism will be compared to what would be expected from the sickness of the component single knockouts. Recent algorithmic work has identified graph-theoretic patterns in this data that can indicate functional modules, and even sets of genes that may occur in compensatory pathways, such as a BPM-type schema first introduced by Kelley and Ideker. However, to date, any algorithms for finding such patterns in the data were implemented internally, with no software being made publically available. Genecentric is a new package that implements a parallelized version of the Leiserson et al. algorithm (J Comput Biol 18:1399-1409, 2011) for generating generalized BPMs from high-throughput genetic interaction data. Given a matrix of weighted epistasis values for a set of double knock-outs, Genecentric returns a list of generalized BPMs that may represent compensatory pathways. Genecentric also has an extension, GenecentricGO, to query FuncAssociate (Bioinformatics 25:3043-3044, 2009) to retrieve GO enrichment statistics on generated BPMs. Python is the only dependency, and our web site provides working examples and documentation. We find that Genecentric can be used to find coherent functional and perhaps compensatory gene sets from high throughput genetic interaction data. Genecentric is made freely available for download under the GPLv2 from http://bcb.cs.tufts.edu/genecentric.

  4. A high-throughput assay of NK cell activity in whole blood and its clinical application

    International Nuclear Information System (INIS)

    Lee, Saet-byul; Cha, Junhoe; Kim, Im-kyung; Yoon, Joo Chun; Lee, Hyo Joon; Park, Sang Woo; Cho, Sunjung; Youn, Dong-Ye; Lee, Heyja; Lee, Choong Hwan; Lee, Jae Myun; Lee, Kang Young; Kim, Jongsun

    2014-01-01

    Graphical abstract: - Highlights: • We demonstrated a simple assay of NK cell activity from whole blood. • The measurement of secreted IFN-γ from NK cell enables high-throughput screening. • The NKA assay was validated by clinical results of colorectal cancer patients. - Abstract: Natural killer (NK) cells are lymphocytes of the innate immune system and have the ability to kill tumor cells and virus-infected cells without prior sensitization. Malignant tumors and viruses have developed, however, strategies to suppress NK cells to escape from their responses. Thus, the evaluation of NK cell activity (NKA) could be invaluable to estimate the status and the outcome of cancers, viral infections, and immune-mediated diseases. Established methods that measure NKA, such as 51 Cr release assay and CD107a degranulation assay, may be used to determine NK cell function, but they are complicated and time-consuming because they require isolation of peripheral blood mononuclear cells (PBMC) or NK cells. In some cases these assays require hazardous material such as radioactive isotopes. To overcome these difficulties, we developed a simple assay that uses whole blood instead of PBMC or isolated NK cells. This novel assay is suitable for high-throughput screening and the monitoring of diseases, because it employs serum of ex vivo stimulated whole blood to detect interferon (IFN)-γ secreted from NK cells as an indicator of NKA. After the stimulation of NK cells, the determination of IFNγ concentration in serum samples by enzyme-linked immunosorbent assay (ELISA) provided a swift, uncomplicated, and high-throughput assay of NKA ex vivo. The NKA results microsatellite stable (MSS) colorectal cancer patients was showed significantly lower NKA, 263.6 ± 54.5 pg/mL compared with healthy subjects, 867.5 ± 50.2 pg/mL (p value <0.0001). Therefore, the NKA could be utilized as a supportive diagnostic marker for microsatellite stable (MSS) colorectal cancer

  5. OptoDyCE: Automated system for high-throughput all-optical dynamic cardiac electrophysiology

    Science.gov (United States)

    Klimas, Aleksandra; Yu, Jinzhu; Ambrosi, Christina M.; Williams, John C.; Bien, Harold; Entcheva, Emilia

    2016-02-01

    In the last two decades, market were due to cardiac toxicity, where unintended interactions with ion channels disrupt the heart's normal electrical function. Consequently, all new drugs must undergo preclinical testing for cardiac liability, adding to an already expensive and lengthy process. Recognition that proarrhythmic effects often result from drug action on multiple ion channels demonstrates a need for integrative and comprehensive measurements. Additionally, patient-specific therapies relying on emerging technologies employing stem-cell derived cardiomyocytes (e.g. induced pluripotent stem-cell-derived cardiomyocytes, iPSC-CMs) require better screening methods to become practical. However, a high-throughput, cost-effective approach for cellular cardiac electrophysiology has not been feasible. Optical techniques for manipulation and recording provide a contactless means of dynamic, high-throughput testing of cells and tissues. Here, we consider the requirements for all-optical electrophysiology for drug testing, and we implement and validate OptoDyCE, a fully automated system for all-optical cardiac electrophysiology. We demonstrate the high-throughput capabilities using multicellular samples in 96-well format by combining optogenetic actuation with simultaneous fast high-resolution optical sensing of voltage or intracellular calcium. The system can also be implemented using iPSC-CMs and other cell-types by delivery of optogenetic drivers, or through the modular use of dedicated light-sensitive somatic cells in conjunction with non-modified cells. OptoDyCE provides a truly modular and dynamic screening system, capable of fully-automated acquisition of high-content information integral for improved discovery and development of new drugs and biologics, as well as providing a means of better understanding of electrical disturbances in the heart.

  6. Blood group genotyping: from patient to high-throughput donor screening.

    Science.gov (United States)

    Veldhuisen, B; van der Schoot, C E; de Haas, M

    2009-10-01

    Blood group antigens, present on the cell membrane of red blood cells and platelets, can be defined either serologically or predicted based on the genotypes of genes encoding for blood group antigens. At present, the molecular basis of many antigens of the 30 blood group systems and 17 human platelet antigens is known. In many laboratories, blood group genotyping assays are routinely used for diagnostics in cases where patient red cells cannot be used for serological typing due to the presence of auto-antibodies or after recent transfusions. In addition, DNA genotyping is used to support (un)-expected serological findings. Fetal genotyping is routinely performed when there is a risk of alloimmune-mediated red cell or platelet destruction. In case of patient blood group antigen typing, it is important that a genotyping result is quickly available to support the selection of donor blood, and high-throughput of the genotyping method is not a prerequisite. In addition, genotyping of blood donors will be extremely useful to obtain donor blood with rare phenotypes, for example lacking a high-frequency antigen, and to obtain a fully typed donor database to be used for a better matching between recipient and donor to prevent adverse transfusion reactions. Serological typing of large cohorts of donors is a labour-intensive and expensive exercise and hampered by the lack of sufficient amounts of approved typing reagents for all blood group systems of interest. Currently, high-throughput genotyping based on DNA micro-arrays is a very feasible method to obtain a large pool of well-typed blood donors. Several systems for high-throughput blood group genotyping are developed and will be discussed in this review.

  7. A high throughput single nucleotide polymorphism multiplex assay for parentage assignment in New Zealand sheep.

    Directory of Open Access Journals (Sweden)

    Shannon M Clarke

    Full Text Available Accurate pedigree information is critical to animal breeding systems to ensure the highest rate of genetic gain and management of inbreeding. The abundance of available genomic data, together with development of high throughput genotyping platforms, means that single nucleotide polymorphisms (SNPs are now the DNA marker of choice for genomic selection studies. Furthermore the superior qualities of SNPs compared to microsatellite markers allows for standardization between laboratories; a property that is crucial for developing an international set of markers for traceability studies. The objective of this study was to develop a high throughput SNP assay for use in the New Zealand sheep industry that gives accurate pedigree assignment and will allow a reduction in breeder input over lambing. This required two phases of development--firstly, a method of extracting quality DNA from ear-punch tissue performed in a high throughput cost efficient manner and secondly a SNP assay that has the ability to assign paternity to progeny resulting from mob mating. A likelihood based approach to infer paternity was used where sires with the highest LOD score (log of the ratio of the likelihood given parentage to likelihood given non-parentage are assigned. An 84 "parentage SNP panel" was developed that assigned, on average, 99% of progeny to a sire in a problem where there were 3,000 progeny from 120 mob mated sires that included numerous half sib sires. In only 6% of those cases was there another sire with at least a 0.02 probability of paternity. Furthermore dam information (either recorded, or by genotyping possible dams was absent, highlighting the SNP test's suitability for paternity testing. Utilization of this parentage SNP assay will allow implementation of progeny testing into large commercial farms where the improved accuracy of sire assignment and genetic evaluations will increase genetic gain in the sheep industry.

  8. A high-throughput assay of NK cell activity in whole blood and its clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Saet-byul [Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cha, Junhoe [ATGen Co. Ltd., Sungnam (Korea, Republic of); Kim, Im-kyung [Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Yoon, Joo Chun [Department of Microbiology, Ewha Womans University School of Medicine, Seoul (Korea, Republic of); Lee, Hyo Joon [Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Sang Woo; Cho, Sunjung; Youn, Dong-Ye; Lee, Heyja; Lee, Choong Hwan [ATGen Co. Ltd., Sungnam (Korea, Republic of); Lee, Jae Myun [Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Kang Young, E-mail: kylee117@yuhs.ac [Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Jongsun, E-mail: jkim63@yuhs.ac [Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-03-14

    Graphical abstract: - Highlights: • We demonstrated a simple assay of NK cell activity from whole blood. • The measurement of secreted IFN-γ from NK cell enables high-throughput screening. • The NKA assay was validated by clinical results of colorectal cancer patients. - Abstract: Natural killer (NK) cells are lymphocytes of the innate immune system and have the ability to kill tumor cells and virus-infected cells without prior sensitization. Malignant tumors and viruses have developed, however, strategies to suppress NK cells to escape from their responses. Thus, the evaluation of NK cell activity (NKA) could be invaluable to estimate the status and the outcome of cancers, viral infections, and immune-mediated diseases. Established methods that measure NKA, such as {sup 51}Cr release assay and CD107a degranulation assay, may be used to determine NK cell function, but they are complicated and time-consuming because they require isolation of peripheral blood mononuclear cells (PBMC) or NK cells. In some cases these assays require hazardous material such as radioactive isotopes. To overcome these difficulties, we developed a simple assay that uses whole blood instead of PBMC or isolated NK cells. This novel assay is suitable for high-throughput screening and the monitoring of diseases, because it employs serum of ex vivo stimulated whole blood to detect interferon (IFN)-γ secreted from NK cells as an indicator of NKA. After the stimulation of NK cells, the determination of IFNγ concentration in serum samples by enzyme-linked immunosorbent assay (ELISA) provided a swift, uncomplicated, and high-throughput assay of NKA ex vivo. The NKA results microsatellite stable (MSS) colorectal cancer patients was showed significantly lower NKA, 263.6 ± 54.5 pg/mL compared with healthy subjects, 867.5 ± 50.2 pg/mL (p value <0.0001). Therefore, the NKA could be utilized as a supportive diagnostic marker for microsatellite stable (MSS) colorectal cancer.

  9. High throughput generated micro-aggregates of chondrocytes stimulate cartilage formation in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    LS Moreira Teixeira

    2012-06-01

    Full Text Available Cell-based cartilage repair strategies such as matrix-induced autologous chondrocyte implantation (MACI could be improved by enhancing cell performance. We hypothesised that micro-aggregates of chondrocytes generated in high-throughput prior to implantation in a defect could stimulate cartilaginous matrix deposition and remodelling. To address this issue, we designed a micro-mould to enable controlled high-throughput formation of micro-aggregates. Morphology, stability, gene expression profiles and chondrogenic potential of micro-aggregates of human and bovine chondrocytes were evaluated and compared to single-cells cultured in micro-wells and in 3D after encapsulation in Dextran-Tyramine (Dex-TA hydrogels in vitro and in vivo. We successfully formed micro-aggregates of human and bovine chondrocytes with highly controlled size, stability and viability within 24 hours. Micro-aggregates of 100 cells presented a superior balance in Collagen type I and Collagen type II gene expression over single cells and micro-aggregates of 50 and 200 cells. Matrix metalloproteinases 1, 9 and 13 mRNA levels were decreased in micro-aggregates compared to single-cells. Histological and biochemical analysis demonstrated enhanced matrix deposition in constructs seeded with micro-aggregates cultured in vitro and in vivo, compared to single-cell seeded constructs. Whole genome microarray analysis and single gene expression profiles using human chondrocytes confirmed increased expression of cartilage-related genes when chondrocytes were cultured in micro-aggregates. In conclusion, we succeeded in controlled high-throughput formation of micro-aggregates of chondrocytes. Compared to single cell-seeded constructs, seeding of constructs with micro-aggregates greatly improved neo-cartilage formation. Therefore, micro-aggregation prior to chondrocyte implantation in current MACI procedures, may effectively accelerate hyaline cartilage formation.

  10. High throughput generated micro-aggregates of chondrocytes stimulate cartilage formation in vitro and in vivo.

    Science.gov (United States)

    Moreira Teixeira, L S; Leijten, J C H; Sobral, J; Jin, R; van Apeldoorn, A A; Feijen, J; van Blitterswijk, C; Dijkstra, P J; Karperien, M

    2012-06-05

    Cell-based cartilage repair strategies such as matrix-induced autologous chondrocyte implantation (MACI) could be improved by enhancing cell performance. We hypothesised that micro-aggregates of chondrocytes generated in high-throughput prior to implantation in a defect could stimulate cartilaginous matrix deposition and remodelling. To address this issue, we designed a micro-mould to enable controlled high-throughput formation of micro-aggregates. Morphology, stability, gene expression profiles and chondrogenic potential of micro-aggregates of human and bovine chondrocytes were evaluated and compared to single-cells cultured in micro-wells and in 3D after encapsulation in Dextran-Tyramine (Dex-TA) hydrogels in vitro and in vivo. We successfully formed micro-aggregates of human and bovine chondrocytes with highly controlled size, stability and viability within 24 hours. Micro-aggregates of 100 cells presented a superior balance in Collagen type I and Collagen type II gene expression over single cells and micro-aggregates of 50 and 200 cells. Matrix metalloproteinases 1, 9 and 13 mRNA levels were decreased in micro-aggregates compared to single-cells. Histological and biochemical analysis demonstrated enhanced matrix deposition in constructs seeded with micro-aggregates cultured in vitro and in vivo, compared to single-cell seeded constructs. Whole genome microarray analysis and single gene expression profiles using human chondrocytes confirmed increased expression of cartilage-related genes when chondrocytes were cultured in micro-aggregates. In conclusion, we succeeded in controlled high-throughput formation of micro-aggregates of chondrocytes. Compared to single cell-seeded constructs, seeding of constructs with micro-aggregates greatly improved neo-cartilage formation. Therefore, micro-aggregation prior to chondrocyte implantation in current MACI procedures, may effectively accelerate hyaline cartilage formation.

  11. Advances in High-Throughput Speed, Low-Latency Communication for Embedded Instrumentation (7th Annual SFAF Meeting, 2012)

    Energy Technology Data Exchange (ETDEWEB)

    Jordan, Scott

    2012-06-01

    Scott Jordan on "Advances in high-throughput speed, low-latency communication for embedded instrumentation" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

  12. HTTK R Package v1.4 - JSS Article on HTTK: R Package for High-Throughput Toxicokinetics

    Data.gov (United States)

    U.S. Environmental Protection Agency — httk: High-Throughput Toxicokinetics Functions and data tables for simulation and statistical analysis of chemical toxicokinetics ("TK") using data obtained from...

  13. State of the Art High-Throughput Approaches to Genotoxicity: Flow Micronucleus, Ames II, GreenScreen and Comet

    Science.gov (United States)

    State of the Art High-Throughput Approaches to Genotoxicity: Flow Micronucleus, Ames II, GreenScreen and Comet (Presented by Dr. Marilyn J. Aardema, Chief Scientific Advisor, Toxicology, Dr. Leon Stankowski, et. al. (6/28/2012)

  14. High Throughput Computing Impact on Meta Genomics (Metagenomics Informatics Challenges Workshop: 10K Genomes at a Time)

    Energy Technology Data Exchange (ETDEWEB)

    Gore, Brooklin

    2011-10-12

    This presentation includes a brief background on High Throughput Computing, correlating gene transcription factors, optical mapping, genotype to phenotype mapping via QTL analysis, and current work on next gen sequencing.

  15. High-Throughput Dietary Exposure Predictions for Chemical Migrants from Food Contact Substances for Use in Chemical Prioritization

    Data.gov (United States)

    U.S. Environmental Protection Agency — Under the ExpoCast program, United States Environmental Protection Agency (EPA) researchers have developed a high-throughput (HT) framework for estimating aggregate...

  16. Roche genome sequencer FLX based high-throughput sequencing of ancient DNA

    DEFF Research Database (Denmark)

    Alquezar-Planas, David E; Fordyce, Sarah Louise

    2012-01-01

    Since the development of so-called "next generation" high-throughput sequencing in 2005, this technology has been applied to a variety of fields. Such applications include disease studies, evolutionary investigations, and ancient DNA. Each application requires a specialized protocol to ensure...... that the data produced is optimal. Although much of the procedure can be followed directly from the manufacturer's protocols, the key differences lie in the library preparation steps. This chapter presents an optimized protocol for the sequencing of fossil remains and museum specimens, commonly referred...

  17. High Throughput Preparation of Aligned Nanofibers Using an Improved Bubble-Electrospinning

    Directory of Open Access Journals (Sweden)

    Liang Yu

    2017-11-01

    Full Text Available An improved bubble-electrospinning, consisting of a cone shaped air nozzle, a copper solution reservoir connected directly to the power generator, and a high speed rotating copper wire drum as a collector, was presented successfully to obtain high throughput preparation of aligned nanofibers. The influences of drum rotation speed on morphology and properties of obtained nanofibers were explored and researched. The results showed that the alignment degree, diameter distribution, and properties of nanofibers were improved with the increase of the drum rotation speed.

  18. Newborn screening for X-linked adrenoleukodystrophy: further evidence high throughput screening is feasible.

    Science.gov (United States)

    Theda, Christiane; Gibbons, Katy; Defor, Todd E; Donohue, Pamela K; Golden, W Christopher; Kline, Antonie D; Gulamali-Majid, Fizza; Panny, Susan R; Hubbard, Walter C; Jones, Richard O; Liu, Anita K; Moser, Ann B; Raymond, Gerald V

    2014-01-01

    X-linked adrenoleukodystrophy (ALD) is characterized by adrenal insufficiency and neurologic involvement with onset at variable ages. Plasma very long chain fatty acids are elevated in ALD; even in asymptomatic patients. We demonstrated previously that liquid chromatography tandem mass spectrometry measuring C26:0 lysophosphatidylcholine reliably identifies affected males. We prospectively applied this method to 4689 newborn blood spot samples; no false positives were observed. We show that high throughput neonatal screening for ALD is methodologically feasible. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Screening and Crystallization Plates for Manual and High-throughput Protein Crystal Growth

    Science.gov (United States)

    Thorne, Robert E. (Inventor); Berejnov, Viatcheslav (Inventor); Kalinin, Yevgeniy (Inventor)

    2010-01-01

    In one embodiment, a crystallization and screening plate comprises a plurality of cells open at a top and a bottom, a frame that defines the cells in the plate, and at least two films. The first film seals a top of the plate and the second film seals a bottom of the plate. At least one of the films is patterned to strongly pin the contact lines of drops dispensed onto it, fixing their position and shape. The present invention also includes methods and other devices for manual and high-throughput protein crystal growth.

  20. High-throughput search for caloric materials: the CaloriCool approach

    Science.gov (United States)

    Zarkevich, N. A.; Johnson, D. D.; Pecharsky, V. K.

    2018-01-01

    The high-throughput search paradigm adopted by the newly established caloric materials consortium—CaloriCool®—with the goal to substantially accelerate discovery and design of novel caloric materials is briefly discussed. We begin with describing material selection criteria based on known properties, which are then followed by heuristic fast estimates, ab initio calculations, all of which has been implemented in a set of automated computational tools and measurements. We also demonstrate how theoretical and computational methods serve as a guide for experimental efforts by considering a representative example from the field of magnetocaloric materials.

  1. High-throughput screening for bioactive components from traditional Chinese medicine.

    Science.gov (United States)

    Zhu, Yanhui; Zhang, Zhiyun; Zhang, Meng; Mais, Dale E; Wang, Ming-Wei

    2010-12-01

    Throughout the centuries, traditional Chinese medicine has been a rich resource in the development of new drugs. Modern drug discovery, which relies increasingly on automated high throughput screening and quick hit-to-lead development, however, is confronted with the challenges of the chemical complexity associated with natural products. New technologies for biological screening as well as library building are in great demand in order to meet the requirements. Here we review the developments in these techniques under the perspective of their applicability in natural product drug discovery. Methods in library building, component characterizing, biological evaluation, and other screening methods including NMR and X-ray diffraction are discussed.

  2. Repurposing a Benchtop Centrifuge for High-Throughput Single-Molecule Force Spectroscopy.

    Science.gov (United States)

    Yang, Darren; Wong, Wesley P

    2018-01-01

    We present high-throughput single-molecule manipulation using a benchtop centrifuge, overcoming limitations common in other single-molecule approaches such as high cost, low throughput, technical difficulty, and strict infrastructure requirements. An inexpensive and compact Centrifuge Force Microscope (CFM) adapted to a commercial centrifuge enables use by nonspecialists, and integration with DNA nanoswitches facilitates both reliable measurements and repeated molecular interrogation. Here, we provide detailed protocols for constructing the CFM, creating DNA nanoswitch samples, and carrying out single-molecule force measurements.

  3. Multiplexed homogeneous proximity ligation assays for high throughput protein biomarker research in serological material

    DEFF Research Database (Denmark)

    Lundberg, Martin; Thorsen, Stine Buch; Assarsson, Erika

    2011-01-01

    A high throughput protein biomarker discovery tool has been developed based on multiplexed proximity ligation assays (PLA) in a homogeneous format in the sense of no washing steps. The platform consists of four 24-plex panels profiling 74 putative biomarkers with sub pM sensitivity each consuming...... sequences are united by DNA ligation upon simultaneous target binding forming a PCR amplicon. Multiplex PLA thereby converts multiple target analytes into real-time PCR amplicons that are individually quantificatied using microfluidic high capacity qPCR in nano liter volumes. The assay shows excellent...

  4. In-Field High-Throughput Phenotyping of Cotton Plant Height Using LiDAR

    OpenAIRE

    Shangpeng Sun; Changying Li; Andrew H. Paterson

    2017-01-01

    A LiDAR-based high-throughput phenotyping (HTP) system was developed for cotton plant phenotyping in the field. The HTP system consists of a 2D LiDAR and an RTK-GPS mounted on a high clearance tractor. The LiDAR scanned three rows of cotton plots simultaneously from the top and the RTK-GPS was used to provide the spatial coordinates of the point cloud during data collection. Configuration parameters of the system were optimized to ensure the best data quality. A height profile for each plot w...

  5. High-throughput creation of micropatterned PDMS surfaces using microscale dual roller casting

    International Nuclear Information System (INIS)

    DiBartolomeo, Franklin J; Ge, Ning; Trinkle, Christine A

    2012-01-01

    This work introduces microscale dual roller casting (MDRC), a novel high-throughput fabrication method for creating continuous micropatterned surfaces using thermosetting polymers. MDRC utilizes a pair of rotating, heated cylindrical molds with microscale surface patterns to cure a continuous microstructured film. Using unmodified polydimethylsiloxane as the thermosetting polymer, we were able to create optically transparent, biocompatible surfaces with submicron patterning fidelity. Compared to other roll-to-roll fabrication processes, this method offers increased flexibility in the types of materials and topography that can be generated, including dual-sided patterning, embedded materials and tunable film thickness. (paper)

  6. Solion ion source for high-efficiency, high-throughput solar cell manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Koo, John, E-mail: john-koo@amat.com; Binns, Brant; Miller, Timothy; Krause, Stephen; Skinner, Wesley; Mullin, James [Applied Materials, Inc., Varian Semiconductor Equipment Business Unit, 35 Dory Road, Gloucester, Massachusetts 01930 (United States)

    2014-02-15

    In this paper, we introduce the Solion ion source for high-throughput solar cell doping. As the source power is increased to enable higher throughput, negative effects degrade the lifetime of the plasma chamber and the extraction electrodes. In order to improve efficiency, we have explored a wide range of electron energies and determined the conditions which best suit production. To extend the lifetime of the source we have developed an in situ cleaning method using only existing hardware. With these combinations, source life-times of >200 h for phosphorous and >100 h for boron ion beams have been achieved while maintaining 1100 cell-per-hour production.

  7. Recent Advances in Nanobiotechnology and High-Throughput Molecular Techniques for Systems Biomedicine

    Science.gov (United States)

    Kim, Eung-Sam; Ahn, Eun Hyun; Chung, Euiheon; Kim, Deok-Ho

    2013-01-01

    Nanotechnology-based tools are beginning to emerge as promising platforms for quantitative high-throughput analysis of live cells and tissues. Despite unprecedented progress made over the last decade, a challenge still lies in integrating emerging nanotechnology-based tools into macroscopic biomedical apparatuses for practical purposes in biomedical sciences. In this review, we discuss the recent advances and limitations in the analysis and control of mechanical, biochemical, fluidic, and optical interactions in the interface areas of nanotechnology-based materials and living cells in both in vitro and in vivo settings. PMID:24258011

  8. Microfluidic Impedance Flow Cytometry Enabling High-Throughput Single-Cell Electrical Property Characterization

    Science.gov (United States)

    Chen, Jian; Xue, Chengcheng; Zhao, Yang; Chen, Deyong; Wu, Min-Hsien; Wang, Junbo

    2015-01-01

    This article reviews recent developments in microfluidic impedance flow cytometry for high-throughput electrical property characterization of single cells. Four major perspectives of microfluidic impedance flow cytometry for single-cell characterization are included in this review: (1) early developments of microfluidic impedance flow cytometry for single-cell electrical property characterization; (2) microfluidic impedance flow cytometry with enhanced sensitivity; (3) microfluidic impedance and optical flow cytometry for single-cell analysis and (4) integrated point of care system based on microfluidic impedance flow cytometry. We examine the advantages and limitations of each technique and discuss future research opportunities from the perspectives of both technical innovation and clinical applications. PMID:25938973

  9. The efficacy of high-throughput sequencing and target enrichment on charred archaeobotanical remains

    DEFF Research Database (Denmark)

    Nistelberger, H. M.; Smith, O.; Wales, Nathan

    2016-01-01

    . It has been suggested that high-throughput sequencing (HTS) technologies coupled with DNA enrichment techniques may overcome some of these limitations. Here we report the findings of HTS and target enrichment on four important archaeological crops (barley, grape, maize and rice) performed in three...... lightly-charred maize cob. Even with target enrichment, this sample failed to yield adequate data required to address fundamental questions in archaeology and biology. We further reanalysed part of an existing dataset on charred plant material, and found all purported endogenous DNA sequences were likely...

  10. High-throughput gated photon counter with two detection windows programmable down to 70 ps width

    Energy Technology Data Exchange (ETDEWEB)

    Boso, Gianluca; Tosi, Alberto, E-mail: alberto.tosi@polimi.it; Zappa, Franco [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Piazza Leonardo Da Vinci 32, 20133 Milano (Italy); Mora, Alberto Dalla [Dipartimento di Fisica, Politecnico di Milano, Piazza Leonardo Da Vinci 32, 20133 Milano (Italy)

    2014-01-15

    We present the design and characterization of a high-throughput gated photon counter able to count electrical pulses occurring within two well-defined and programmable detection windows. We extensively characterized and validated this instrument up to 100 Mcounts/s and with detection window width down to 70 ps. This instrument is suitable for many applications and proves to be a cost-effective and compact alternative to time-correlated single-photon counting equipment, thanks to its easy configurability, user-friendly interface, and fully adjustable settings via a Universal Serial Bus (USB) link to a remote computer.

  11. High-throughput mapping of cell-wall polymers within and between plants using novel microarrays

    DEFF Research Database (Denmark)

    Moller, Isabel Eva; Sørensen, Iben; Bernal Giraldo, Adriana Jimena

    2007-01-01

    We describe here a methodology that enables the occurrence of cell-wall glycans to be systematically mapped throughout plants in a semi-quantitative high-throughput fashion. The technique (comprehensive microarray polymer profiling, or CoMPP) integrates the sequential extraction of glycans from...... analysis of mutant and wild-type plants, as demonstrated here for the Arabidopsis thaliana mutants fra8, mur1 and mur3. CoMPP was also applied to Physcomitrella patens cell walls and was validated by carbohydrate linkage analysis. These data provide new insights into the structure and functions of plant...

  12. AELAS: Automatic ELAStic property derivations via high-throughput first-principles computation

    Science.gov (United States)

    Zhang, S. H.; Zhang, R. F.

    2017-11-01

    The elastic properties are fundamental and important for crystalline materials as they relate to other mechanical properties, various thermodynamic qualities as well as some critical physical properties. However, a complete set of experimentally determined elastic properties is only available for a small subset of known materials, and an automatic scheme for the derivations of elastic properties that is adapted to high-throughput computation is much demanding. In this paper, we present the AELAS code, an automated program for calculating second-order elastic constants of both two-dimensional and three-dimensional single crystal materials with any symmetry, which is designed mainly for high-throughput first-principles computation. Other derivations of general elastic properties such as Young's, bulk and shear moduli as well as Poisson's ratio of polycrystal materials, Pugh ratio, Cauchy pressure, elastic anisotropy and elastic stability criterion, are also implemented in this code. The implementation of the code has been critically validated by a lot of evaluations and tests on a broad class of materials including two-dimensional and three-dimensional materials, providing its efficiency and capability for high-throughput screening of specific materials with targeted mechanical properties. Program Files doi:http://dx.doi.org/10.17632/f8fwg4j9tw.1 Licensing provisions: BSD 3-Clause Programming language: Fortran Nature of problem: To automate the calculations of second-order elastic constants and the derivations of other elastic properties for two-dimensional and three-dimensional materials with any symmetry via high-throughput first-principles computation. Solution method: The space-group number is firstly determined by the SPGLIB code [1] and the structure is then redefined to unit cell with IEEE-format [2]. Secondly, based on the determined space group number, a set of distortion modes is automatically specified and the distorted structure files are generated

  13. High throughput diffractive multi-beam femtosecond laser processing using a spatial light modulator

    Energy Technology Data Exchange (ETDEWEB)

    Kuang Zheng [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom)], E-mail: z.kuang@liv.ac.uk; Perrie, Walter [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom); Leach, Jonathan [Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Sharp, Martin; Edwardson, Stuart P. [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom); Padgett, Miles [Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Dearden, Geoff; Watkins, Ken G. [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom)

    2008-12-30

    High throughput femtosecond laser processing is demonstrated by creating multiple beams using a spatial light modulator (SLM). The diffractive multi-beam patterns are modulated in real time by computer generated holograms (CGHs), which can be calculated by appropriate algorithms. An interactive LabVIEW program is adopted to generate the relevant CGHs. Optical efficiency at this stage is shown to be {approx}50% into first order beams and real time processing has been carried out at 50 Hz refresh rate. Results obtained demonstrate high precision surface micro-structuring on silicon and Ti6Al4V with throughput gain >1 order of magnitude.

  14. High-throughput telomere length quantification by FISH and its application to human population studies.

    Science.gov (United States)

    Canela, Andrés; Vera, Elsa; Klatt, Peter; Blasco, María A

    2007-03-27

    A major limitation of studies of the relevance of telomere length to cancer and age-related diseases in human populations and to the development of telomere-based therapies has been the lack of suitable high-throughput (HT) assays to measure telomere length. We have developed an automated HT quantitative telomere FISH platform, HT quantitative FISH (Q-FISH), which allows the quantification of telomere length as well as percentage of short telomeres in large human sample sets. We show here that this technique provides the accuracy and sensitivity to uncover associations between telomere length and human disease.

  15. High-throughput screening for industrial enzyme production hosts by droplet microfluidics

    DEFF Research Database (Denmark)

    Sjostrom, Staffan L.; Bai, Yunpeng; Huang, Mingtao

    2014-01-01

    A high-throughput method for single cell screening by microfluidic droplet sorting is applied to a whole-genome mutated yeast cell library yielding improved production hosts of secreted industrial enzymes. The sorting method is validated by enriching a yeast strain 14 times based on its α......-amylase production, close to the theoretical maximum enrichment. Furthermore, a 105 member yeast cell library is screened yielding a clone with a more than 2-fold increase in α-amylase production. The increase in enzyme production results from an improvement of the cellular functions of the production host...

  16. A high-throughput method for quantifying metabolically active yeast cells

    DEFF Research Database (Denmark)

    Nandy, Subir Kumar; Knudsen, Peter Boldsen; Rosenkjær, Alexander

    2015-01-01

    By redesigning the established methylene blue reduction test for bacteria and yeast, we present a cheap and efficient methodology for quantitative physiology of eukaryotic cells applicable for high-throughput systems. Validation of themethod in fermenters and highthroughput systems proved....... The drop in metabolic activity associated with the diauxic shift in yeast proved more pronounced for the MBRT-derived curve compared with OD curves, consistent with a dramatic shift in the ratio between live and dead cells at this metabolic event. This method provides a tool with numerous applications, e.......g. characterizing the death phase of stationary phase cultures, or in drug screens with pathogenic yeasts....

  17. Targeted Capture and High-Throughput Sequencing Using Molecular Inversion Probes (MIPs).

    Science.gov (United States)

    Cantsilieris, Stuart; Stessman, Holly A; Shendure, Jay; Eichler, Evan E

    2017-01-01

    Molecular inversion probes (MIPs) in combination with massively parallel DNA sequencing represent a versatile, yet economical tool for targeted sequencing of genomic DNA. Several thousand genomic targets can be selectively captured using long oligonucleotides containing unique targeting arms and universal linkers. The ability to append sequencing adaptors and sample-specific barcodes allows large-scale pooling and subsequent high-throughput sequencing at relatively low cost per sample. Here, we describe a "wet bench" protocol detailing the capture and subsequent sequencing of >2000 genomic targets from 192 samples, representative of a single lane on the Illumina HiSeq 2000 platform.

  18. High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates

    KAUST Repository

    Stoltz, Brian

    2010-06-14

    The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a non-polar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard reaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a β-keto-ester derived- and an α-phenyl cyclohexanone-derived enol carbonate.

  19. 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.

  20. High-throughput method for optimum solubility screening for homogeneity and crystallization of proteins

    Science.gov (United States)

    Kim, Sung-Hou [Moraga, CA; Kim, Rosalind [Moraga, CA; Jancarik, Jamila [Walnut Creek, CA

    2012-01-31

    An optimum solubility screen in which a panel of buffers and many additives are provided in order to obtain the most homogeneous and monodisperse protein condition for protein crystallization. The present methods are useful for proteins that aggregate and cannot be concentrated prior to setting up crystallization screens. A high-throughput method using the hanging-drop method and vapor diffusion equilibrium and a panel of twenty-four buffers is further provided. Using the present methods, 14 poorly behaving proteins have been screened, resulting in 11 of the proteins having highly improved dynamic light scattering results allowing concentration of the proteins, and 9 were crystallized.