WorldWideScience

Sample records for computational drug design

  1. Computer aided drug design

    Science.gov (United States)

    Jain, A.

    2017-08-01

    Computer based method can help in discovery of leads and can potentially eliminate chemical synthesis and screening of many irrelevant compounds, and in this way, it save time as well as cost. Molecular modeling systems are powerful tools for building, visualizing, analyzing and storing models of complex molecular structure that can help to interpretate structure activity relationship. The use of various techniques of molecular mechanics and dynamics and software in Computer aided drug design along with statistics analysis is powerful tool for the medicinal chemistry to synthesis therapeutic and effective drugs with minimum side effect.

  2. Computer Aided Drug Design: Success and Limitations.

    Science.gov (United States)

    Baig, Mohammad Hassan; Ahmad, Khurshid; Roy, Sudeep; Ashraf, Jalaluddin Mohammad; Adil, Mohd; Siddiqui, Mohammad Haris; Khan, Saif; Kamal, Mohammad Amjad; Provazník, Ivo; Choi, Inho

    2016-01-01

    Over the last few decades, computer-aided drug design has emerged as a powerful technique playing a crucial role in the development of new drug molecules. Structure-based drug design and ligand-based drug design are two methods commonly used in computer-aided drug design. In this article, we discuss the theory behind both methods, as well as their successful applications and limitations. To accomplish this, we reviewed structure based and ligand based virtual screening processes. Molecular dynamics simulation, which has become one of the most influential tool for prediction of the conformation of small molecules and changes in their conformation within the biological target, has also been taken into account. Finally, we discuss the principles and concepts of molecular docking, pharmacophores and other methods used in computer-aided drug design.

  3. Computer-Aided Drug Design in Epigenetics

    Directory of Open Access Journals (Sweden)

    Wenchao Lu

    2018-03-01

    Full Text Available Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation, and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field.

  4. Computer-Aided Drug Design in Epigenetics

    Science.gov (United States)

    Lu, Wenchao; Zhang, Rukang; Jiang, Hao; Zhang, Huimin; Luo, Cheng

    2018-01-01

    Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation, and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field. PMID:29594101

  5. Computer-Aided Drug Design in Epigenetics

    Science.gov (United States)

    Lu, Wenchao; Zhang, Rukang; Jiang, Hao; Zhang, Huimin; Luo, Cheng

    2018-03-01

    Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field.

  6. Computer-aided drug design at Boehringer Ingelheim

    Science.gov (United States)

    Muegge, Ingo; Bergner, Andreas; Kriegl, Jan M.

    2017-03-01

    Computer-Aided Drug Design (CADD) is an integral part of the drug discovery endeavor at Boehringer Ingelheim (BI). CADD contributes to the evaluation of new therapeutic concepts, identifies small molecule starting points for drug discovery, and develops strategies for optimizing hit and lead compounds. The CADD scientists at BI benefit from the global use and development of both software platforms and computational services. A number of computational techniques developed in-house have significantly changed the way early drug discovery is carried out at BI. In particular, virtual screening in vast chemical spaces, which can be accessed by combinatorial chemistry, has added a new option for the identification of hits in many projects. Recently, a new framework has been implemented allowing fast, interactive predictions of relevant on and off target endpoints and other optimization parameters. In addition to the introduction of this new framework at BI, CADD has been focusing on the enablement of medicinal chemists to independently perform an increasing amount of molecular modeling and design work. This is made possible through the deployment of MOE as a global modeling platform, allowing computational and medicinal chemists to freely share ideas and modeling results. Furthermore, a central communication layer called the computational chemistry framework provides broad access to predictive models and other computational services.

  7. The role of water molecules in computational drug design.

    Science.gov (United States)

    de Beer, Stephanie B A; Vermeulen, Nico P E; Oostenbrink, Chris

    2010-01-01

    Although water molecules are small and only consist of two different atom types, they play various roles in cellular systems. This review discusses their influence on the binding process between biomacromolecular targets and small molecule ligands and how this influence can be modeled in computational drug design approaches. Both the structure and the thermodynamics of active site waters will be discussed as these influence the binding process significantly. Structurally conserved waters cannot always be determined experimentally and if observed, it is not clear if they will be replaced upon ligand binding, even if sufficient space is available. Methods to predict the presence of water in protein-ligand complexes will be reviewed. Subsequently, we will discuss methods to include water in computational drug research. Either as an additional factor in automated docking experiments, or explicitly in detailed molecular dynamics simulations, the effect of water on the quality of the simulations is significant, but not easily predicted. The most detailed calculations involve estimates of the free energy contribution of water molecules to protein-ligand complexes. These calculations are computationally demanding, but give insight in the versatility and importance of water in ligand binding.

  8. Virtual fragment preparation for computational fragment-based drug design.

    Science.gov (United States)

    Ludington, Jennifer L

    2015-01-01

    Fragment-based drug design (FBDD) has become an important component of the drug discovery process. The use of fragments can accelerate both the search for a hit molecule and the development of that hit into a lead molecule for clinical testing. In addition to experimental methodologies for FBDD such as NMR and X-ray Crystallography screens, computational techniques are playing an increasingly important role. The success of the computational simulations is due in large part to how the database of virtual fragments is prepared. In order to prepare the fragments appropriately it is necessary to understand how FBDD differs from other approaches and the issues inherent in building up molecules from smaller fragment pieces. The ultimate goal of these calculations is to link two or more simulated fragments into a molecule that has an experimental binding affinity consistent with the additive predicted binding affinities of the virtual fragments. Computationally predicting binding affinities is a complex process, with many opportunities for introducing error. Therefore, care should be taken with the fragment preparation procedure to avoid introducing additional inaccuracies.This chapter is focused on the preparation process used to create a virtual fragment database. Several key issues of fragment preparation which affect the accuracy of binding affinity predictions are discussed. The first issue is the selection of the two-dimensional atomic structure of the virtual fragment. Although the particular usage of the fragment can affect this choice (i.e., whether the fragment will be used for calibration, binding site characterization, hit identification, or lead optimization), general factors such as synthetic accessibility, size, and flexibility are major considerations in selecting the 2D structure. Other aspects of preparing the virtual fragments for simulation are the generation of three-dimensional conformations and the assignment of the associated atomic point charges.

  9. Heuristic lipophilicity potential for computer-aided rational drug design

    Science.gov (United States)

    Du, Qishi; Arteca, Gustavo A.; Mezey, Paul G.

    1997-09-01

    In this contribution we suggest a heuristic molecular lipophilicitypotential (HMLP), which is a structure-based technique requiring noempirical indices of atomic lipophilicity. The input data used in thisapproach are molecular geometries and molecular surfaces. The HMLP is amodified electrostatic potential, combined with the averaged influences fromthe molecular environment. Quantum mechanics is used to calculate theelectron density function ρ(r) and the electrostatic potential V(r), andfrom this information a lipophilicity potential L(r) is generated. The HMLPis a unified lipophilicity and hydrophilicity potential. The interactions ofdipole and multipole moments, hydrogen bonds, and charged atoms in amolecule are included in the hydrophilic interactions in this model. TheHMLP is used to study hydrogen bonds and water-octanol partitioncoefficients in several examples. The calculated results show that the HMLPgives qualitatively and quantitatively correct, as well as chemicallyreasonable, results in cases where comparisons are available. Thesecomparisons indicate that the HMLP has advantages over the empiricallipophilicity potential in many aspects. The HMLP is a three-dimensional andeasily visualizable representation of molecular lipophilicity, suggested asa potential tool in computer-aided three-dimensional drug design.

  10. Using Free Computational Resources to Illustrate the Drug Design Process in an Undergraduate Medicinal Chemistry Course

    Science.gov (United States)

    Rodrigues, Ricardo P.; Andrade, Saulo F.; Mantoani, Susimaire P.; Eifler-Lima, Vera L.; Silva, Vinicius B.; Kawano, Daniel F.

    2015-01-01

    Advances in, and dissemination of, computer technologies in the field of drug research now enable the use of molecular modeling tools to teach important concepts of drug design to chemistry and pharmacy students. A series of computer laboratories is described to introduce undergraduate students to commonly adopted "in silico" drug design…

  11. Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer's Disease Therapeutic Agents.

    Science.gov (United States)

    Llorach-Pares, Laura; Nonell-Canals, Alfons; Sanchez-Martinez, Melchor; Avila, Conxita

    2017-11-27

    Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A-G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium , against various protein kinases involved in Alzheimer's disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs.

  12. Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.

    Science.gov (United States)

    Bian, Yuemin; Xie, Xiang-Qun Sean

    2018-04-09

    Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

  13. Biomedical data integration in computational drug design and bioinformatics.

    Science.gov (United States)

    Seoane, Jose A; Aguiar-Pulido, Vanessa; Munteanu, Cristian R; Rivero, Daniel; Rabunal, Juan R; Dorado, Julian; Pazos, Alejandro

    2013-03-01

    In recent years, in the post genomic era, more and more data is being generated by biological high throughput technologies, such as proteomics and transcriptomics. This omics data can be very useful, but the real challenge is to analyze all this data, as a whole, after integrating it. Biomedical data integration enables making queries to different, heterogeneous and distributed biomedical data sources. Data integration solutions can be very useful not only in the context of drug design, but also in biomedical information retrieval, clinical diagnosis, system biology, etc. In this review, we analyze the most common approaches to biomedical data integration, such as federated databases, data warehousing, multi-agent systems and semantic technology, as well as the solutions developed using these approaches in the past few years.

  14. Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

    Directory of Open Access Journals (Sweden)

    Lucianna Helene Santos

    2015-11-01

    Full Text Available Reverse transcriptase (RT is a multifunctional enzyme in the human immunodeficiency virus (HIV-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

  15. Computational drug designing of fungal pigments as potential aromatase inhibitors

    Directory of Open Access Journals (Sweden)

    Nighat Fatima

    2014-12-01

    Full Text Available The existing aromatase inhibitors produced unwelcome effects impose the discovery of novel drugs with privileged selectivity, a reduced amount of toxicity and humanizing potency. In this study, we illuminate the binding mode of polyketide azaphilanoid pigments monascin, ankaflavin, monascorubrin and monascorubramine isolated from Monascus fungus to the aromatase by molecular docking. The 3-dimensional structure of aromatase enzyme (PDB: 4KQ8 was obtained from the Protein Data Bank. PatchDock docking software was used to analyze structural complexes of the aromatase with monascus pigments. Comparatively, the AutoGrid model presented the most briskly constructive binding mode of monascin to aromatase. Docked energies in kcal/mol are: monascin;-13.2; monascorubramine:-12.8, monascorubrin:-12.3; ankaflavin: -10.5. These outcomes exposed these ligands could be potential drugs to treat hormone dependent breast cancer.

  16. Ebola virus: A gap in drug design and discovery - experimental and computational perspective.

    Science.gov (United States)

    Balmith, Marissa; Faya, Mbuso; Soliman, Mahmoud E S

    2017-03-01

    The Ebola virus, formally known as the Ebola hemorrhagic fever, is an acute viral syndrome causing sporadic outbreaks that have ravaged West Africa. Due to its extreme virulence and highly transmissible nature, Ebola has been classified as a category A bioweapon organism. Only recently have vaccine or drug regimens for the Ebola virus been developed, including Zmapp and peptides. In addition, existing drugs which have been repurposed toward anti-Ebola virus activity have been re-examined and are seen to be promising candidates toward combating Ebola. Drug development involving computational tools has been widely employed toward target-based drug design. Screening large libraries have greatly stimulated research toward effective anti-Ebola virus drug regimens. Current emphasis has been placed on the investigation of host proteins and druggable viral targets. There is a huge gap in the literature regarding guidelines in the discovery of Ebola virus inhibitors, which may be due to the lack of information on the Ebola drug targets, binding sites, and mechanism of action of the virus. This review focuses on Ebola virus inhibitors, drugs which could be repurposed to combat the Ebola virus, computational methods which study drug-target interactions as well as providing further insight into the mode of action of the Ebola virus. © 2016 John Wiley & Sons A/S.

  17. Using computer-aided drug design and medicinal chemistry strategies in the fight against diabetes.

    Science.gov (United States)

    Semighini, Evandro P; Resende, Jonathan A; de Andrade, Peterson; Morais, Pedro A B; Carvalho, Ivone; Taft, Carlton A; Silva, Carlos H T P

    2011-04-01

    The aim of this work is to present a simple, practical and efficient protocol for drug design, in particular Diabetes, which includes selection of the illness, good choice of a target as well as a bioactive ligand and then usage of various computer aided drug design and medicinal chemistry tools to design novel potential drug candidates in different diseases. We have selected the validated target dipeptidyl peptidase IV (DPP-IV), whose inhibition contributes to reduce glucose levels in type 2 diabetes patients. The most active inhibitor with complex X-ray structure reported was initially extracted from the BindingDB database. By using molecular modification strategies widely used in medicinal chemistry, besides current state-of-the-art tools in drug design (including flexible docking, virtual screening, molecular interaction fields, molecular dynamics, ADME and toxicity predictions), we have proposed 4 novel potential DPP-IV inhibitors with drug properties for Diabetes control, which have been supported and validated by all the computational tools used herewith.

  18. Fragment informatics and computational fragment-based drug design: an overview and update.

    Science.gov (United States)

    Sheng, Chunquan; Zhang, Wannian

    2013-05-01

    Fragment-based drug design (FBDD) is a promising approach for the discovery and optimization of lead compounds. Despite its successes, FBDD also faces some internal limitations and challenges. FBDD requires a high quality of target protein and good solubility of fragments. Biophysical techniques for fragment screening necessitate expensive detection equipment and the strategies for evolving fragment hits to leads remain to be improved. Regardless, FBDD is necessary for investigating larger chemical space and can be applied to challenging biological targets. In this scenario, cheminformatics and computational chemistry can be used as alternative approaches that can significantly improve the efficiency and success rate of lead discovery and optimization. Cheminformatics and computational tools assist FBDD in a very flexible manner. Computational FBDD can be used independently or in parallel with experimental FBDD for efficiently generating and optimizing leads. Computational FBDD can also be integrated into each step of experimental FBDD and help to play a synergistic role by maximizing its performance. This review will provide critical analysis of the complementarity between computational and experimental FBDD and highlight recent advances in new algorithms and successful examples of their applications. In particular, fragment-based cheminformatics tools, high-throughput fragment docking, and fragment-based de novo drug design will provide the focus of this review. We will also discuss the advantages and limitations of different methods and the trends in new developments that should inspire future research. © 2012 Wiley Periodicals, Inc.

  19. Binding Mode and Induced Fit Predictions for Prospective Computational Drug Design.

    Science.gov (United States)

    Grebner, Christoph; Iegre, Jessica; Ulander, Johan; Edman, Karl; Hogner, Anders; Tyrchan, Christian

    2016-04-25

    Computer-aided drug design plays an important role in medicinal chemistry to obtain insights into molecular mechanisms and to prioritize design strategies. Although significant improvement has been made in structure based design, it still remains a key challenge to accurately model and predict induced fit mechanisms. Most of the current available techniques either do not provide sufficient protein conformational sampling or are too computationally demanding to fit an industrial setting. The current study presents a systematic and exhaustive investigation of predicting binding modes for a range of systems using PELE (Protein Energy Landscape Exploration), an efficient and fast protein-ligand sampling algorithm. The systems analyzed (cytochrome P, kinase, protease, and nuclear hormone receptor) exhibit different complexities of ligand induced fit mechanisms and protein dynamics. The results are compared with results from classical molecular dynamics simulations and (induced fit) docking. This study shows that ligand induced side chain rearrangements and smaller to medium backbone movements are captured well in PELE. Large secondary structure rearrangements, however, remain challenging for all employed techniques. Relevant binding modes (ligand heavy atom RMSD PELE method within a few hours of simulation, positioning PELE as a tool applicable for rapid drug design cycles.

  20. History and evolution of the pharmacophore concept in computer-aided drug design.

    Science.gov (United States)

    Güner, Osman F

    2002-12-01

    With computer-aided drug design established as an integral part of the lead discovery and optimization process, pharmacophores have become a focal point for conceptualizing and understanding receptor-ligand interactions. In the structure-based design process, pharmacophores can be used to align molecules based on the three-dimensional arrangement of chemical features or to develop predictive models (e.g., 3D-QSAR) that correlate with the experimental activities of a given training set. Pharmacophores can be also used as search queries for retrieving potential leads from structural databases, for designing molecules with specific desired attributes, or as fingerprints for assessing similarity and diversity of molecules. This review article presents a historical perspective on the evolution and use of the pharmacophore concept in the pharmaceutical, biotechnology, and fragrances industry with published examples of how the technology has contributed and advanced the field.

  1. Integrated Teaching of Structure-Based Drug Design and Biopharmaceutics: A Computer-Based Approach

    Science.gov (United States)

    Sutch, Brian T.; Romero, Rebecca M.; Neamati, Nouri; Haworth, Ian S.

    2012-01-01

    Rational drug design requires expertise in structural biology, medicinal chemistry, physiology, and related fields. In teaching structure-based drug design, it is important to develop an understanding of the need for early recognition of molecules with "drug-like" properties as a key component. That is, it is not merely sufficient to teach…

  2. The multiple roles of computational chemistry in fragment-based drug design

    Science.gov (United States)

    Law, Richard; Barker, Oliver; Barker, John J.; Hesterkamp, Thomas; Godemann, Robert; Andersen, Ole; Fryatt, Tara; Courtney, Steve; Hallett, Dave; Whittaker, Mark

    2009-08-01

    Fragment-based drug discovery (FBDD) represents a change in strategy from the screening of molecules with higher molecular weights and physical properties more akin to fully drug-like compounds, to the screening of smaller, less complex molecules. This is because it has been recognised that fragment hit molecules can be efficiently grown and optimised into leads, particularly after the binding mode to the target protein has been first determined by 3D structural elucidation, e.g. by NMR or X-ray crystallography. Several studies have shown that medicinal chemistry optimisation of an already drug-like hit or lead compound can result in a final compound with too high molecular weight and lipophilicity. The evolution of a lower molecular weight fragment hit therefore represents an attractive alternative approach to optimisation as it allows better control of compound properties. Computational chemistry can play an important role both prior to a fragment screen, in producing a target focussed fragment library, and post-screening in the evolution of a drug-like molecule from a fragment hit, both with and without the available fragment-target co-complex structure. We will review many of the current developments in the area and illustrate with some recent examples from successful FBDD discovery projects that we have conducted.

  3. Computational Biology Tools for Identifying Specific Ligand Binding Residues for Novel Agrochemical and Drug Design.

    Science.gov (United States)

    Neshich, Izabella Agostinho Pena; Nishimura, Leticia; de Moraes, Fabio Rogerio; Salim, Jose Augusto; Villalta-Romero, Fabian; Borro, Luiz; Yano, Inacio Henrique; Mazoni, Ivan; Tasic, Ljubica; Jardine, Jose Gilberto; Neshich, Goran

    2015-01-01

    The term "agrochemicals" is used in its generic form to represent a spectrum of pesticides, such as insecticides, fungicides or bactericides. They contain active components designed for optimized pest management and control, therefore allowing for economically sound and labor efficient agricultural production. A "drug" on the other side is a term that is used for compounds designed for controlling human diseases. Although drugs are subjected to much more severe testing and regulation procedures before reaching the market, they might contain exactly the same active ingredient as certain agrochemicals, what is the case described in present work, showing how a small chemical compound might be used to control pathogenicity of Gram negative bacteria Xylella fastidiosa which devastates citrus plantations, as well as for control of, for example, meningitis in humans. It is also clear that so far the production of new agrochemicals is not benefiting as much from the in silico new chemical compound identification/discovery as pharmaceutical production. Rational drug design crucially depends on detailed knowledge of structural information about the receptor (target protein) and the ligand (drug/agrochemical). The interaction between the two molecules is the subject of analysis that aims to understand relationship between structure and function, mainly deciphering some fundamental elements of the nanoenvironment where the interaction occurs. In this work we will emphasize the role of understanding nanoenvironmental factors that guide recognition and interaction of target protein and its function modifier, an agrochemical or a drug. The repertoire of nanoenvironment descriptors is used for two selected and specific cases we have approached in order to offer a technological solution for some very important problems that needs special attention in agriculture: elimination of pathogenicity of a bacterium which is attacking citrus plants and formulation of a new fungicide. Finally

  4. G-LoSA: An efficient computational tool for local structure-centric biological studies and drug design.

    Science.gov (United States)

    Lee, Hui Sun; Im, Wonpil

    2016-04-01

    Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G-LoSA. G-LoSA aligns protein local structures in a sequence order independent way and provides a GA-score, a chemical feature-based and size-independent structure similarity score. Our benchmark validation shows the robust performance of G-LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure-centric comparative biology studies. In particular, G-LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G-LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer-aided drug design. We hope that G-LoSA can be a useful computational method for exploring interesting biological problems through large-scale comparison of protein local structures and facilitating drug discovery research and development. G-LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. © 2016 The Protein Society.

  5. New Computational Approaches for NMR-based Drug Design: A Protocol for Ligand Docking to Flexible Target Sites

    International Nuclear Information System (INIS)

    Gracia, Luis; Speidel, Joshua A.; Weinstein, Harel

    2006-01-01

    NMR-based drug design has met with some success in the last decade, as illustrated in numerous instances by Fesik's ''ligand screening by NMR'' approach. Ongoing efforts to generalize this success have led us to the development of a new paradigm in which quantitative computational approaches are being integrated with NMR derived data and biological assays. The key component of this work is the inclusion of the intrinsic dynamic quality of NMR structures in theoretical models and its use in docking. A new computational protocol is introduced here, designed to dock small molecule ligands to flexible proteins derived from NMR structures. The algorithm makes use of a combination of simulated annealing monte carlo simulations (SA/MC) and a mean field potential informed by the NMR data. The new protocol is illustrated in the context of an ongoing project aimed at developing new selective inhibitors for the PCAF bromodomains that interact with HIV Tat

  6. G‐LoSA: An efficient computational tool for local structure‐centric biological studies and drug design

    Science.gov (United States)

    2016-01-01

    Abstract Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G‐LoSA. G‐LoSA aligns protein local structures in a sequence order independent way and provides a GA‐score, a chemical feature‐based and size‐independent structure similarity score. Our benchmark validation shows the robust performance of G‐LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure‐centric comparative biology studies. In particular, G‐LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G‐LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer‐aided drug design. We hope that G‐LoSA can be a useful computational method for exploring interesting biological problems through large‐scale comparison of protein local structures and facilitating drug discovery research and development. G‐LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. PMID:26813336

  7. Opportunities for Russian Nuclear Weapons Institute developing computer-aided design programs for pharmaceutical drug discovery. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-09-23

    The goal of this study is to determine whether physicists at the Russian Nuclear Weapons Institute can profitably service the need for computer aided drug design (CADD) programs. The Russian physicists` primary competitive advantage is their ability to write particularly efficient code able to work with limited computing power; a history of working with very large, complex modeling systems; an extensive knowledge of physics and mathematics, and price competitiveness. Their primary competitive disadvantage is their lack of biology, and cultural and geographic issues. The first phase of the study focused on defining the competitive landscape, primarily through interviews with and literature searches on the key providers of CADD software. The second phase focused on users of CADD technology to determine deficiencies in the current product offerings, to understand what product they most desired, and to define the potential demand for such a product.

  8. Computational approaches for the study of serotonin and its membrane transporter SERT: implications for drug design in neurological sciences.

    Science.gov (United States)

    Pratuangdejkul, J; Schneider, B; Launay, J-M; Kellermann, O; Manivet, P

    2008-01-01

    Serotonin (5-hydroxytryptamine, 5-HT), a monoamine neurotransmitter of the central nervous and peripheral systems (CNS), plays a critical role in a wide variety of physiological and behavioral processes. In the serotonergic system, deregulation of the tightly controlled extracellular concentration of 5-HT appears to be at the origin of a host of metabolic and psychiatric disorders. A key step that regulates 5-HT external level is the re-uptake of 5-HT into cells by the 5-HT transporter (SERT), which is besides the target of numerous drugs interacting with the serotonergic system. Therapeutic strategies have mainly focused on the development of compounds that block the activity of SERT, for instance reuptake inhibitors (e.g. tricyclics, "selective" serotonin reuptake inhibitors) and in the past, specific substrate-type releasers (e.g. amphetamine and cocaine derivatives). Today, generation of new drugs targetting SERT with enhanced selectivity and reduced toxicity is one of the most challenging tasks in drug design. In this context, studies aiming at characterizing the physicochemical properties of 5-HT as well as the biological active conformation of SERT are a prerequisite to the design of new leads. However, the absence of a high-resolution 3D-structure for SERT has hampered the design of new transporter inhibitors. Using computational approaches, numerous efforts were made to shed light on the structure of 5-HT and its transporter. In this review, we compared several in silico methods dedicated to the modeling of 5-HT and SERT with an emphasis on i) quantum chemistry for study of 5-HT conformation and ii) ligand-based (QSAR and pharmacophore models) and transporter-based (homology models) approaches for studying SERT molecule. In addition, we discuss some methodological aspects of the computational work in connection with the construction of putative but reliable 3D structural models of SERT that may help to predict the mechanisms of neurotransmitter transport.

  9. State-of-the-art and dissemination of computational tools for drug-design purposes: a survey among Italian academics and industrial institutions.

    Science.gov (United States)

    Artese, Anna; Alcaro, Stefano; Moraca, Federica; Reina, Rocco; Ventura, Marzia; Costantino, Gabriele; Beccari, Andrea R; Ortuso, Francesco

    2013-05-01

    During the first edition of the Computationally Driven Drug Discovery meeting, held in November 2011 at Dompé Pharma (L'Aquila, Italy), a questionnaire regarding the diffusion and the use of computational tools for drug-design purposes in both academia and industry was distributed among all participants. This is a follow-up of a previously reported investigation carried out among a few companies in 2007. The new questionnaire implemented five sections dedicated to: research group identification and classification; 18 different computational techniques; software information; hardware data; and economical business considerations. In this article, together with a detailed history of the different computational methods, a statistical analysis of the survey results that enabled the identification of the prevalent computational techniques adopted in drug-design projects is reported and a profile of the computational medicinal chemist currently working in academia and pharmaceutical companies in Italy is highlighted.

  10. [Designer drugs in Jutland].

    Science.gov (United States)

    Simonsen, K W; Kaa, E

    2001-04-16

    The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs. All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined. MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly. MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

  11. Computation-based virtual screening for designing novel antimalarial drugs by targeting falcipain-III: a structure-based drug designing approach.

    Science.gov (United States)

    Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna

    2013-01-01

    Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having

  12. From chemical graphs in computer-aided drug design to general Markov-Galvez indices of drug-target, proteome, drug-parasitic disease, technological, and social-legal networks.

    Science.gov (United States)

    Riera-Fernández, Pablo; Munteanu, Cristian R; Dorado, Julian; Martin-Romalde, Raquel; Duardo-Sanchez, Aliuska; González-Diaz, Humberto

    2011-12-01

    Complex Networks are useful in solving problems in drug research and industry, developing mathematical representations of different systems. These systems move in a wide range from relatively simple graph representations of drug molecular structures to large systems. We can cite for instance, drug-target protein interaction networks, drug policy legislation networks, or drug treatment in large geographical disease spreading networks. In any case, all these networks have essentially the same components: nodes (atoms, drugs, proteins, microorganisms and/or parasites, geographical areas, drug policy legislations, etc.) and edges (chemical bonds, drug-target interactions, drug-parasite treatment, drug use, etc.). Consequently, we can use the same type of numeric parameters called Topological Indices (TIs) to describe the connectivity patterns in all these kinds of Complex Networks despite the nature of the object they represent. The main reason for this success of TIs is the high flexibility of this theory to solve in a fast but rigorous way many apparently unrelated problems in all these disciplines. Another important reason for the success of TIs is that using these parameters as inputs we can find Quantitative Structure-Property Relationships (QSPR) models for different kind of problems in Computer-Aided Drug Design (CADD). Taking into account all the above-mentioned aspects, the present work is aimed at offering a common background to all the manuscripts presented in this special issue. In so doing, we make a review of the most common types of complex networks involving drugs or their targets. In addition, we review both classic TIs that have been used to describe the molecular structure of drugs and/or larger complex networks. Next, we use for the first time a Markov chain model to generalize Galvez TIs to higher order analogues coined here as the Markov-Galvez TIs of order k (MGk). Lastly, we illustrate the calculation of MGk values for different classes of

  13. Heuristic lipophilicity potential for computer-aided rational drug design: Optimizations of screening functions and parameters

    Science.gov (United States)

    Du, Qishi; Mezey, Paul G.

    1998-09-01

    In this research we test and compare three possible atom-basedscreening functions used in the heuristic molecular lipophilicity potential(HMLP). Screening function 1 is a power distance-dependent function, b_{{i}} /| {R_{{i}}- r} |^γ, screening function 2is an exponential distance-dependent function, biexp(-| {R_i- r} |/d_0 , and screening function 3 is aweighted distance-dependent function, {{sign}}( {b_i } ){{exp}}ξ ( {| {R_i- r} |/| {b_i } |} )For every screening function, the parameters (γ ,d0, and ξ are optimized using 41 common organic molecules of 4 types of compounds:aliphatic alcohols, aliphatic carboxylic acids, aliphatic amines, andaliphatic alkanes. The results of calculations show that screening function3 cannot give chemically reasonable results, however, both the powerscreening function and the exponential screening function give chemicallysatisfactory results. There are two notable differences between screeningfunctions 1 and 2. First, the exponential screening function has largervalues in the short distance than the power screening function, thereforemore influence from the nearest neighbors is involved using screeningfunction 2 than screening function 1. Second, the power screening functionhas larger values in the long distance than the exponential screeningfunction, therefore screening function 1 is effected by atoms at longdistance more than screening function 2. For screening function 1, thesuitable range of parameter d0 is 1.5 < d0 < 3.0, and d0 = 2.0 is recommended. HMLP developed in this researchprovides a potential tool for computer-aided three-dimensional drugdesign.

  14. Computational neuropharmacology: dynamical approaches in drug discovery.

    Science.gov (United States)

    Aradi, Ildiko; Erdi, Péter

    2006-05-01

    Computational approaches that adopt dynamical models are widely accepted in basic and clinical neuroscience research as indispensable tools with which to understand normal and pathological neuronal mechanisms. Although computer-aided techniques have been used in pharmaceutical research (e.g. in structure- and ligand-based drug design), the power of dynamical models has not yet been exploited in drug discovery. We suggest that dynamical system theory and computational neuroscience--integrated with well-established, conventional molecular and electrophysiological methods--offer a broad perspective in drug discovery and in the search for novel targets and strategies for the treatment of neurological and psychiatric diseases.

  15. Crystallography and Drug Design

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 12. Crystallography and Drug Design. K Suguna. General Article Volume 19 Issue 12 December 2014 pp 1093-1103. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/019/12/1093-1103. Keywords.

  16. Computational methods in drug discovery

    OpenAIRE

    Sumudu P. Leelananda; Steffen Lindert

    2016-01-01

    The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery project...

  17. Computational molecular modeling and structural rationalization for the design of a drug-loaded PLLA/PVA biopolymeric membrane

    International Nuclear Information System (INIS)

    Sibeko, B; Pillay, V; Choonara, Y E; Khan, R A; Danckwerts, M P; Modi, G; Iyuke, S E; Naidoo, D

    2009-01-01

    The purpose of this study was to design, characterize and assess the influence of triethanolamine (TEA) on the physicomechanical properties and release of methotrexate (MTX) from a composite biopolymeric membrane. Conjugated poly(L-lactic acid) (PLLA) and poly(vinyl alcohol) (PVA) membranes were prepared by immersion precipitation with and without the addition of TEA. Drug entrapment efficiency (DEE) and release studies were performed in phosphate buffered saline (pH 7.4, 37 deg. C). Scanning electron microscopy elucidated the membrane surface morphology. Computational and structural molecular modeling rationalized the potential mechanisms of membrane formation and MTX release. Bi-axial force-distance (F-D) extensibility profiles were generated to determine the membrane toughness, elasticity and fracturability. Membranes were significantly toughened by the addition of TEA as a discrete rubbery phase within the co-polymer matrix. MTX-TEA-PLLA-PVA membranes were tougher (F = 89 N) and more extensible (D = 8.79 mm) compared to MTX-PLLA-PVA (F = 35 N, D = 3.7 mm) membranes as a greater force of extension and fracture distance were required (N = 10). DEE values were relatively high (>80%, N = 5) for both formulations. Photomicrographs revealed distinct crystalline layered morphologies with macro-pores. MTX was released by tri-phasic kinetics with a lower fractional release of MTX from MTX-TEA-PLLA-PVA membranes compared to MTX-PLLA-PVA. TEA provided a synergistic approach to improving the membrane physicomechanical properties and modulation of MTX release. The composite biopolymeric membrane may therefore be suitable for the novel delivery of MTX in the treatment of chronic primary central nervous system lymphoma.

  18. Computational methods in drug discovery

    Directory of Open Access Journals (Sweden)

    Sumudu P. Leelananda

    2016-12-01

    Full Text Available The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed.

  19. Spirocyclic ureas: orally bioavailable 11 beta-HSD1 inhibitors identified by computer-aided drug design.

    Science.gov (United States)

    Tice, Colin M; Zhao, Wei; Xu, Zhenrong; Cacatian, Salvacion T; Simpson, Robert D; Ye, Yuan-Jie; Singh, Suresh B; McKeever, Brian M; Lindblom, Peter; Guo, Joan; Krosky, Paula M; Kruk, Barbara A; Berbaum, Jennifer; Harrison, Richard K; Johnson, Judith J; Bukhtiyarov, Yuri; Panemangalore, Reshma; Scott, Boyd B; Zhao, Yi; Bruno, Joseph G; Zhuang, Linghang; McGeehan, Gerard M; He, Wei; Claremon, David A

    2010-02-01

    Structure-guided drug design led to the identification of a class of spirocyclic ureas which potently inhibit human 11beta-HSD1 in vitro. Lead compound 10j was shown to be orally bioavailable in three species, distributed into adipose tissue in the mouse, and its (R) isomer 10j2 was efficacious in a primate pharmacodynamic model. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  20. Computational Amphiphilic Materials for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naresh eThota

    2015-10-01

    Full Text Available Amphiphilic materials can assemble into a wide variety of morphologies and have emerged as a novel class of candidates for drug delivery. Along with a large number of experiments reported, computational studies have been also conducted in this field. At an atomistic/molecular level, computations can facilitate quantitative understanding of experimental observations and secure fundamental interpretation of underlying phenomena. This review summarizes the recent computational efforts on amphiphilic copolymers and peptides for drug delivery. Atom-resolution and time-resolved insights are provided from bottom-up to microscopically elucidate the mechanisms of drug loading/release, which are indispensable in the rational screening and design of new amphiphiles for high-efficacy drug delivery.

  1. iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan.

    Science.gov (United States)

    Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

    2011-06-01

    The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

  2. iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

    Science.gov (United States)

    Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

    2011-06-01

    The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

  3. Design of Computer Experiments

    DEFF Research Database (Denmark)

    Dehlendorff, Christian

    The main topic of this thesis is design and analysis of computer and simulation experiments and is dealt with in six papers and a summary report. Simulation and computer models have in recent years received increasingly more attention due to their increasing complexity and usability. Software...... packages make the development of rather complicated computer models using predefined building blocks possible. This implies that the range of phenomenas that are analyzed by means of a computer model has expanded significantly. As the complexity grows so does the need for efficient experimental designs...... and analysis methods, since the complex computer models often are expensive to use in terms of computer time. The choice of performance parameter is an important part of the analysis of computer and simulation models and Paper A introduces a new statistic for waiting times in health care units. The statistic...

  4. Drug Design and Emotion

    Science.gov (United States)

    Folkers, Gerd; Wittwer, Amrei

    2007-11-01

    "Geteiltes Leid ist halbes Leid." The old German proverb reflects the fact that sharing a bad emotion or feeling with someone else may lower the psychological strain of the person experiencing sorrow, mourning or anger. On the other hand the person showing empathy will take literally a load from its counterpart, up to physiological reaction of the peripheral and central nervous pain system. Though subjective, mental and physical states can be shared. Visual perception of suffering may be important but also narrative description plays a role, all our senses are mixing in. It is hypothetized that literature, art and humanities allow this overlap. A change of mental states can lead to empirically observable effects as it is the case for the effect of role identity or placebo on pain perception. Antidepressants and other therapeutics are another choice to change the mental and bodily states. Their development follows today's notion of "rationality" in the design of therapeutics and is characterized solely by an atomic resolution approach to understand drug activity. Since emotional states and physiological states are entangled, given the difficulty of a physical description of emotion, the future rational drug design should encompass mental states as well.

  5. Computational Protein Design

    DEFF Research Database (Denmark)

    Johansson, Kristoffer Enøe

    Proteins are the major functional group of molecules in biology. The impact of protein science on medicine and chemical productions is rapidly increasing. However, the greatest potential remains to be realized. The fi eld of protein design has advanced computational modeling from a tool of support...... to a central method that enables new developments. For example, novel enzymes with functions not found in natural proteins have been de novo designed to give enough activity for experimental optimization. This thesis presents the current state-of-the-art within computational design methods together...... with a novel method based on probability theory. With the aim of assembling a complete pipeline for protein design, this work touches upon several aspects of protein design. The presented work is the computational half of a design project where the other half is dedicated to the experimental part...

  6. Resilient computer system design

    CERN Document Server

    Castano, Victor

    2015-01-01

    This book presents a paradigm for designing new generation resilient and evolving computer systems, including their key concepts, elements of supportive theory, methods of analysis and synthesis of ICT with new properties of evolving functioning, as well as implementation schemes and their prototyping. The book explains why new ICT applications require a complete redesign of computer systems to address challenges of extreme reliability, high performance, and power efficiency. The authors present a comprehensive treatment for designing the next generation of computers, especially addressing safety-critical, autonomous, real time, military, banking, and wearable health care systems.   §  Describes design solutions for new computer system - evolving reconfigurable architecture (ERA) that is free from drawbacks inherent in current ICT and related engineering models §  Pursues simplicity, reliability, scalability principles of design implemented through redundancy and re-configurability; targeted for energy-,...

  7. Applications of the NRGsuite and the Molecular Docking Software FlexAID in Computational Drug Discovery and Design.

    Science.gov (United States)

    Morency, Louis-Philippe; Gaudreault, Francis; Najmanovich, Rafael

    2018-01-01

    Docking simulations help us understand molecular interactions. Here we present a hands-on tutorial to utilize FlexAID (Flexible Artificial Intelligence Docking), an open source molecular docking software between ligands such as small molecules or peptides and macromolecules such as proteins and nucleic acids. The tutorial uses the NRGsuite PyMOL plugin graphical user interface to set up and visualize docking simulations in real time as well as detect and refine target cavities. The ease of use of FlexAID and the NRGsuite combined with its superior performance relative to widely used docking software provides nonexperts with an important tool to understand molecular interactions with direct applications in structure-based drug design and virtual high-throughput screening.

  8. Computational protein design: a review

    International Nuclear Information System (INIS)

    Coluzza, Ivan

    2017-01-01

    Proteins are one of the most versatile modular assembling systems in nature. Experimentally, more than 110 000 protein structures have been identified and more are deposited every day in the Protein Data Bank. Such an enormous structural variety is to a first approximation controlled by the sequence of amino acids along the peptide chain of each protein. Understanding how the structural and functional properties of the target can be encoded in this sequence is the main objective of protein design. Unfortunately, rational protein design remains one of the major challenges across the disciplines of biology, physics and chemistry. The implications of solving this problem are enormous and branch into materials science, drug design, evolution and even cryptography. For instance, in the field of drug design an effective computational method to design protein-based ligands for biological targets such as viruses, bacteria or tumour cells, could give a significant boost to the development of new therapies with reduced side effects. In materials science, self-assembly is a highly desired property and soon artificial proteins could represent a new class of designable self-assembling materials. The scope of this review is to describe the state of the art in computational protein design methods and give the reader an outline of what developments could be expected in the near future. (topical review)

  9. Computer aided product design

    DEFF Research Database (Denmark)

    Constantinou, Leonidas; Bagherpour, Khosrow; Gani, Rafiqul

    1996-01-01

    A general methodology for Computer Aided Product Design (CAPD) with specified property constraints which is capable of solving a large range of problems is presented. The methodology employs the group contribution approach, generates acyclic, cyclic and aromatic compounds of various degrees......-liquid equilibria (LLE), solid-liquid equilibria (SLE) and gas solubility. Finally, a computer program based on the extended methodology has been developed and the results from five case studies highlighting various features of the methodology are presented....

  10. Computational design of drug candidates for influenza A virus subtype H1N1 by inhibiting the viral neuraminidase-1 enzyme

    Directory of Open Access Journals (Sweden)

    Tambunan Usman Sumo Friend

    2014-06-01

    Full Text Available It is critical to seek potential alternative treatments for H1N1 infections by inhibiting neuraminidase-1 enzyme. One of the viable options for inhibiting the activity of neuraminidase- 1 is peptide drug design. In order to increase peptide stability, cyclization is necessary to prevent its digestion by protease enzyme. Cyclization of peptide ligands by formation of disulfide bridges is preferable for designing inhibitors of neuraminidase-1 because of their high activity and specificity. Here we designed ligands by using molecular docking, drug scan and dynamics computational methods. Based on our docking results, short polypeptides of cystein-arginine-methionine-tyrosine- -proline-cysteine (CRMYPC and cysteine-arginine-aspargine- phenylalanine-proline-cysteine (CRNFPC have good residual interactions with the target and the binding energy ΔGbinding of -31.7402 and -31.0144 kcal mol-1, respectively. These values are much lower than those of the standards, and it means that both ligands are more accessible to ligand-receptor binding. Based on drug scan results, both of these ligands are neither mutagenic nor carcinogenic. They also show good oral bioavailability. Moreover, both ligands show relatively stable molecular dynamics progression of RMSD vs. time plot. However, based on our metods, the CRMYPC ligand has sufficient hydrogen bonding interactions with residues of the active side of neuraminidase-1 and can be therefore proposed as a potential inhibitor of neuraminidase-1

  11. Computer aided design

    International Nuclear Information System (INIS)

    Barache, J.M.; Beltranda, G.; Blanc, P.

    1987-01-01

    In order to ensure that the data transmitted to the managment system is of the required quality and consistent with the general control command protocols, computer aided design (CAD) was employed for level N4. One describes the use of CAD for the control system of N4 [fr

  12. Inhibiting and Remodeling Toxic Amyloid-Beta Oligomer Formation Using a Computationally Designed Drug Molecule That Targets Alzheimer's Disease

    Science.gov (United States)

    Downey, Matthew A.; Giammona, Maxwell J.; Lang, Christian A.; Buratto, Steven K.; Singh, Ambuj; Bowers, Michael T.

    2018-04-01

    Alzheimer's disease (AD) is rapidly reaching epidemic status among a burgeoning aging population. Much evidence suggests the toxicity of this amyloid disease is most influenced by the formation of soluble oligomeric forms of amyloid β-protein, particularly the 42-residue alloform (Aβ42). Developing potential therapeutics in a directed, streamlined approach to treating this disease is necessary. Here we utilize the joint pharmacophore space (JPS) model to design a new molecule [AC0107] incorporating structural characteristics of known Aβ inhibitors, blood-brain barrier permeability, and limited toxicity. To test the molecule's efficacy experimentally, we employed ion mobility mass spectrometry (IM-MS) to discover [AC0107] inhibits the formation of the toxic Aβ42 dodecamer at both high (1:10) and equimolar concentrations of inhibitor. Atomic force microscopy (AFM) experiments reveal that [AC0107] prevents further aggregation of Aβ42, destabilizes preformed fibrils, and reverses Aβ42 aggregation. This trend continues for long-term interaction times of 2 days until only small aggregates remain with virtually no fibrils or higher order oligomers surviving. Pairing JPS with IM-MS and AFM presents a powerful and effective first step for AD drug development.

  13. Drug plan design incentives among Medicare prescription drug plans.

    Science.gov (United States)

    Huskamp, Haiden A; Keating, Nancy L; Dalton, Jesse B; Chernew, Michael E; Newhouse, Joseph P

    2014-07-01

    Medicare Advantage prescription drug plans (MA-PDs) and standalone prescription drug plans (PDPs) face different incentives for plan design resulting from the scope of covered benefits (only outpatient drugs for PDPs versus all drug and nondrug services for Medicare Advantage [MA]/MA-PDs). The objective is to begin to explore how MA-PDs and PDPs may be responding to their different incentives related to benefit design. We compared 2012 PDP and MA-PD average formulary coverage, prior authorization (PA) or step therapy use, and copayment requirements for drugs in 6 classes used commonly among Medicare beneficiaries. We primarily used 2012 Prescription Drug Plan Formulary and Pharmacy Network Files and MA enrollment data. 2011 Truven Health MarketScan claims were used to estimate drug prices and to compute drug market share. Average coverage and PA/step rates, and average copayment requirements, were weighted by plan enrollment and drug market share. MA-PDs are generally more likely to cover and less likely to require PA/step for brand name drugs with generic alternatives than PDPs, and MA-PDs often have lower copayment requirements for these drugs. For brands without generics, we generally found no differences in average rates of coverage or PA/step, but MA-PDs were more likely to cover all brands without generics in a class. We found modest, confirmatory evidence suggesting that PDPs and MA-PDs respond to different incentives for plan design. Future research is needed to understand the factors that influence Medicare drug plan design decisions.

  14. Crystallography and Drug Design

    Indian Academy of Sciences (India)

    IAS Admin

    is of immense help in developing drugs for specific diseases by targeting molecules ... tions, or selected from a large pool of available libraries and the binding strengths can ... was identified to be caused by a virus named later as the human.

  15. Rational drug design paradigms: the odyssey for designing better drugs.

    Science.gov (United States)

    Kellici, Tahsin; Ntountaniotis, Dimitrios; Vrontaki, Eleni; Liapakis, George; Moutevelis-Minakakis, Panagiota; Kokotos, George; Hadjikakou, Sotiris; Tzakos, Andreas G; Afantitis, Antreas; Melagraki, Georgia; Bryant, Sharon; Langer, Thierry; Di Marzo, Vincenzo; Mavromoustakos, Thomas

    2015-01-01

    Due to the time and effort requirements for the development of a new drug, and the high attrition rates associated with this developmental process, there is an intense effort by academic and industrial researchers to find novel ways for more effective drug development schemes. The first step in the discovery process of a new drug is the identification of the lead compound. The modern research tendency is to avoid the synthesis of new molecules based on chemical intuition, which is time and cost consuming, and instead to apply in silico rational drug design. This approach reduces the consumables and human personnel involved in the initial steps of the drug design. In this review real examples from our research activity aiming to discover new leads will be given for various dire warnings diseases. There is no recipe to follow for discovering new leads. The strategy to be followed depends on the knowledge of the studied system and the experience of the researchers. The described examples constitute successful and unsuccessful efforts and reflect the reality which medicinal chemists have to face in drug design and development. The drug stability is also discussed in both organic molecules and metallotherapeutics. This is an important issue in drug discovery as drug metabolism in the body can lead to various toxic and undesired molecules.

  16. Fragment-based docking: development of the CHARMMing Web user interface as a platform for computer-aided drug design.

    Science.gov (United States)

    Pevzner, Yuri; Frugier, Emilie; Schalk, Vinushka; Caflisch, Amedeo; Woodcock, H Lee

    2014-09-22

    Web-based user interfaces to scientific applications are important tools that allow researchers to utilize a broad range of software packages with just an Internet connection and a browser. One such interface, CHARMMing (CHARMM interface and graphics), facilitates access to the powerful and widely used molecular software package CHARMM. CHARMMing incorporates tasks such as molecular structure analysis, dynamics, multiscale modeling, and other techniques commonly used by computational life scientists. We have extended CHARMMing's capabilities to include a fragment-based docking protocol that allows users to perform molecular docking and virtual screening calculations either directly via the CHARMMing Web server or on computing resources using the self-contained job scripts generated via the Web interface. The docking protocol was evaluated by performing a series of "re-dockings" with direct comparison to top commercial docking software. Results of this evaluation showed that CHARMMing's docking implementation is comparable to many widely used software packages and validates the use of the new CHARMM generalized force field for docking and virtual screening.

  17. Exploring Natural Products from the Biodiversity of Pakistan for Computational Drug Discovery Studies: Collection, Optimization, Design and Development of A Chemical Database (ChemDP).

    Science.gov (United States)

    Mirza, Shaher Bano; Bokhari, Habib; Fatmi, Muhammad Qaiser

    2015-01-01

    Pakistan possesses a rich and vast source of natural products (NPs). Some of these secondary metabolites have been identified as potent therapeutic agents. However, the medicinal usage of most of these compounds has not yet been fully explored. The discoveries for new scaffolds of NPs as inhibitors of certain enzymes or receptors using advanced computational drug discovery approaches are also limited due to the unavailability of accurate 3D structures of NPs. An organized database incorporating all relevant information, therefore, can facilitate to explore the medicinal importance of the metabolites from Pakistani Biodiversity. The Chemical Database of Pakistan (ChemDP; release 01) is a fully-referenced, evolving, web-based, virtual database which has been designed and developed to introduce natural products (NPs) and their derivatives from the biodiversity of Pakistan to Global scientific communities. The prime aim is to provide quality structures of compounds with relevant information for computer-aided drug discovery studies. For this purpose, over 1000 NPs have been identified from more than 400 published articles, for which 2D and 3D molecular structures have been generated with a special focus on their stereochemistry, where applicable. The PM7 semiempirical quantum chemistry method has been used to energy optimize the 3D structure of NPs. The 2D and 3D structures can be downloaded as .sdf, .mol, .sybyl, .mol2, and .pdb files - readable formats by many chemoinformatics/bioinformatics software packages. Each entry in ChemDP contains over 100 data fields representing various molecular, biological, physico-chemical and pharmacological properties, which have been properly documented in the database for end users. These pieces of information have been either manually extracted from the literatures or computationally calculated using various computational tools. Cross referencing to a major data repository i.e. ChemSpider has been made available for overlapping

  18. Designing with computational intelligence

    CERN Document Server

    Lopes, Heitor; Mourelle, Luiza

    2017-01-01

    This book discusses a number of real-world applications of computational intelligence approaches. Using various examples, it demonstrates that computational intelligence has become a consolidated methodology for automatically creating new competitive solutions to complex real-world problems. It also presents a concise and efficient synthesis of different systems using computationally intelligent techniques.

  19. Quantum Computational Studies of Electron Transfer in Respiratory Complex III and its Application for Designing New Mitocan Drugs

    Science.gov (United States)

    Hagras, Muhammad Ahmed

    electron of a bound QH2 molecule transfers to [2Fe-2S] cluster of the Rieske domain, docked at the proximal docking site, and another electron transfers to heme b L , which subsequently passes it to heme bH , and finally to Q or SQ molecule bound at the Qi-site 4. Rieske domain undergoes a domain movement 22 A to bind at the distal docking site, where [2Fe-2S] cluster passes its electron to heme c1, which in turn passes it to heme c of the water-soluble cytochrome c carrier 3c, 5 (which shuttles it to cytochrome c oxidase, complex IV). In the current compiled work presented in the subsequent chapters, we deployed a stacking tiers hierarchy where each chapter's work presents a foundation for the next one. In chapter 1, we first present different methods to calculate tunneling currents in proteins including a new derivation method for the inter-atomic tunneling current method. In addition, we show the results of the inter-atomic tunneling current theory on models based on heme bL-heme bH redox pair system in bc1 complex. Afterwards, in chapter 2, we examine the electron tunneling pathways 6 between different intra-monomeric and inter-monomeric redox centers of bc1 complex, including its electron carriers - ubiquinol, ubiquinone, and cytochrome c molecules, using the well-studied coarse-grained interatomic method of the tunneling current theory 7. Going through the different tunneling pathways in bc1 complex, we discovered a pair of internal switches that modulate the electron transfer rate which we discuss in full details in chapter 3. Motivated by the discovery of those internal switches, we discuss in chapter 4 the discovery of a new binding pocket (designated as NonQ-site or NQ-site for short) in bc 1 complex which is located at the opposite side of the enzyme with respect to Qo site. In contrast to Qo site, however, the NQ-site penetrates deeply in the cytochrome b domain and reaches very closely the LH region. Hence the NQ-site provides a suitable binding pocket for

  20. Computational Studies of Drug Resistance

    DEFF Research Database (Denmark)

    da Silva Martins, João Miguel

    Drug resistance has been an increasing problem in patient treatment and drug development. Starting in the last century and becoming a major worry in the medical and scienti c communities in the early part of the current millennium, major research must be performed to address the issues of viral...... is of the utmost importance in developing better and less resistance-inducing drugs. A drug's in uence can be characterized in many diff erent ways, however, and the approaches I take in this work re ect those same different in uences. This is what I try to achieve in this work, through seemingly unrelated...... approaches that come together in the study of drug's and their in uence on proteins and vice-versa. In part I, I aim to understand through combined theoretical ensemble analysis and free energy calculations the e ects mutations have over the binding anity and function of the M2 proton channel. This research...

  1. Pyrimidines in antimalarial drug design

    CSIR Research Space (South Africa)

    Moleele, SS

    2008-09-01

    Full Text Available of the routes attempted are shown in Scheme 1. Pyrimidines In Antimalarial Drug Design S S Moleele1, D Gravestock1, A L Rousseau1, R L Van Zyl2 1Discovery Chemistry, CSIR, Biosciences, Private Bag X2, Modderfontein, 1645, South Africa; SMoleele@csir.co.za 2...

  2. Computer-Aided Drug Design

    Science.gov (United States)

    Stowe, Ryan; Elvey, Jacob

    2016-01-01

    Chemistry in high school is often presented as a jumbled mass of topics drawn from inorganic, analytical, and physical sub-disciplines. With no central theme to build on, students may have trouble grasping the chemical sciences as a coherent field. In this article, Stowe and Elvey describe an activity that integrates different facets of chemistry…

  3. Digital design and computer architecture

    CERN Document Server

    Harris, David

    2010-01-01

    Digital Design and Computer Architecture is designed for courses that combine digital logic design with computer organization/architecture or that teach these subjects as a two-course sequence. Digital Design and Computer Architecture begins with a modern approach by rigorously covering the fundamentals of digital logic design and then introducing Hardware Description Languages (HDLs). Featuring examples of the two most widely-used HDLs, VHDL and Verilog, the first half of the text prepares the reader for what follows in the second: the design of a MIPS Processor. By the end of D

  4. Drug design: Insights from atomistic simulations

    International Nuclear Information System (INIS)

    Collu, F.; Spiga, E.; Kumar, A.; Hajjar, E.; Vargiu, A.V.; Ceccarelli, M.; Ruggerone, P.

    2009-01-01

    Computer simulations have become a widely used and powerful tool to study the behaviour of many-particle and many-interaction systems and processes such as nucleic acid dynamics, drug-DNA interactions, enzymatic processes, membrane, antibiotics. The increased reliability of computational techniques has made possible to plane a bottom-up approach in drug design, i.e. designing molecules with improved properties starting from the knowledge of the molecular mechanisms. However, the in silico techniques have to face the fact that the number of degrees of freedom involved in biological systems is very large while the time scale of several biological processes is not accessible to standard simulations. Algorithms and methods have been developed and are still under construction to bridge these gaps. Here we review the activities of our group focussed on the time-scale bottleneck and, in particular, on the use of the meta dynamics scheme that allows the investigation of rare events in reasonable computer time without reducing the accuracy of the calculation. In particular, we have devoted particular attention to the characterization at microscopic level of translocation of antibiotics through membrane pores, aiming at the identification of structural and dynamical features helpful for a rational drug design.

  5. In silico fragment-based drug design.

    Science.gov (United States)

    Konteatis, Zenon D

    2010-11-01

    In silico fragment-based drug design (FBDD) is a relatively new approach inspired by the success of the biophysical fragment-based drug discovery field. Here, we review the progress made by this approach in the last decade and showcase how it complements and expands the capabilities of biophysical FBDD and structure-based drug design to generate diverse, efficient drug candidates. Advancements in several areas of research that have enabled the development of in silico FBDD and some applications in drug discovery projects are reviewed. The reader is introduced to various computational methods that are used for in silico FBDD, the fragment library composition for this technique, special applications used to identify binding sites on the surface of proteins and how to assess the druggability of these sites. In addition, the reader will gain insight into the proper application of this approach from examples of successful programs. In silico FBDD captures a much larger chemical space than high-throughput screening and biophysical FBDD increasing the probability of developing more diverse, patentable and efficient molecules that can become oral drugs. The application of in silico FBDD holds great promise for historically challenging targets such as protein-protein interactions. Future advances in force fields, scoring functions and automated methods for determining synthetic accessibility will all aid in delivering more successes with in silico FBDD.

  6. Computational Design of Urban Layouts

    KAUST Repository

    Wonka, Peter

    2015-10-07

    A fundamental challenge in computational design is to compute layouts by arranging a set of shapes. In this talk I will present recent urban modeling projects with applications in computer graphics, urban planning, and architecture. The talk will look at different scales of urban modeling (streets, floorplans, parcels). A common challenge in all these modeling problems are functional and aesthetic constraints that should be respected. The talk also highlights interesting links to geometry processing problems, such as field design and quad meshing.

  7. Computational materials design

    International Nuclear Information System (INIS)

    Snyder, R.L.

    1999-01-01

    Full text: Trial and error experimentation is an extremely expensive route to the development of new materials. The coming age of reduced defense funding will dramatically alter the way in which advanced materials have developed. In the absence of large funding we must concentrate on reducing the time and expense that the R and D of a new material consumes. This may be accomplished through the development of computational materials science. Materials are selected today by comparing the technical requirements to the materials databases. When existing materials cannot meet the requirements we explore new systems to develop a new material using experimental databases like the PDF. After proof of concept, the scaling of the new material to manufacture requires evaluating millions of parameter combinations to optimize the performance of the new device. Historically this process takes 10 to 20 years and requires hundreds of millions of dollars. The development of a focused set of computational tools to predict the final properties of new materials will permit the exploration of new materials systems with only a limited amount of materials characterization. However, to bound computational extrapolations, the experimental formulations and characterization will need to be tightly coupled to the computational tasks. The required experimental data must be obtained by dynamic, in-situ, very rapid characterization. Finally, to evaluate the optimization matrix required to manufacture the new material, very rapid in situ analysis techniques will be essential to intelligently monitor and optimize the formation of a desired microstructure. Techniques and examples for the rapid real-time application of XRPD and optical microscopy will be shown. Recent developments in the cross linking of the world's structural and diffraction databases will be presented as the basis for the future Total Pattern Analysis by XRPD. Copyright (1999) Australian X-ray Analytical Association Inc

  8. Designing computer programs

    CERN Document Server

    Haigh, Jim

    1994-01-01

    This is a book for students at every level who are learning to program for the first time - and for the considerable number who learned how to program but were never taught to structure their programs. The author presents a simple set of guidelines that show the programmer how to design in a manageable structure from the outset. The method is suitable for most languages, and is based on the widely used 'JSP' method, to which the student may easily progress if it is needed at a later stage.Most language specific texts contain very little if any information on design, whilst books on des

  9. Fragment-based drug design.

    Science.gov (United States)

    Feyfant, Eric; Cross, Jason B; Paris, Kevin; Tsao, Désirée H H

    2011-01-01

    Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process.

  10. Computer-aided design and computer science technology

    Science.gov (United States)

    Fulton, R. E.; Voigt, S. J.

    1976-01-01

    A description is presented of computer-aided design requirements and the resulting computer science advances needed to support aerospace design. The aerospace design environment is examined, taking into account problems of data handling and aspects of computer hardware and software. The interactive terminal is normally the primary interface between the computer system and the engineering designer. Attention is given to user aids, interactive design, interactive computations, the characteristics of design information, data management requirements, hardware advancements, and computer science developments.

  11. Recent progress in computational approaches to studying the M2 proton channel and its implication to drug design against influenza viruses.

    Science.gov (United States)

    Du, Qi-Shi; Huang, Ri-Bo

    2012-05-01

    For quite a long period of time in history, many intense efforts have been made to determine the 3D (three-dimensional) structure of the M2 proton channel. The reason why the M2 proton channel has attracted so many attentions is because (1) it is the key for really understanding the life cycle of influenza viruses, and (2) it is indispensable for conducting rational drug design against the flu viruses. Recently, the long-sough 3D structures of the M2 proton channels for both influenza A and B viruses were consecutively successfully determined by the high-resolution NMR spectroscopy (Schnell J.R. and Chou, J.J., Nature, 2008, 451: 591-595; Wang, J., Pielak, R.M., McClintock, M.A., and Chou, J.J., Nature Structural & Molecular Biology, 2009,16: 1267-1271). Such a milestone work has provided a solid structural basis for in-depth understanding the action mechanism of the M2 channel and rationally designing effective drugs against influenza viruses. This review is devoted to, with the focus on the M2 proton channel of influenza A, addressing a series of relevant problems, such as how to correctly understand the novel allosteric inhibition mechanism inferred from the NMR structure that is completely different from the traditional view, what the possible impacts are to the previous functional studies in this area, and what kind of new strategy can be stimulated for drug development against influenza.

  12. Drug repurposing: translational pharmacology, chemistry, computers and the clinic.

    Science.gov (United States)

    Issa, Naiem T; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2013-01-01

    The process of discovering a pharmacological compound that elicits a desired clinical effect with minimal side effects is a challenge. Prior to the advent of high-performance computing and large-scale screening technologies, drug discovery was largely a serendipitous endeavor, as in the case of thalidomide for erythema nodosum leprosum or cancer drugs in general derived from flora located in far-reaching geographic locations. More recently, de novo drug discovery has become a more rationalized process where drug-target-effect hypotheses are formulated on the basis of already known compounds/protein targets and their structures. Although this approach is hypothesis-driven, the actual success has been very low, contributing to the soaring costs of research and development as well as the diminished pharmaceutical pipeline in the United States. In this review, we discuss the evolution in computational pharmacology as the next generation of successful drug discovery and implementation in the clinic where high-performance computing (HPC) is used to generate and validate drug-target-effect hypotheses completely in silico. The use of HPC would decrease development time and errors while increasing productivity prior to in vitro, animal and human testing. We highlight approaches in chemoinformatics, bioinformatics as well as network biopharmacology to illustrate potential avenues from which to design clinically efficacious drugs. We further discuss the implications of combining these approaches into an integrative methodology for high-accuracy computational predictions within the context of drug repositioning for the efficient streamlining of currently approved drugs back into clinical trials for possible new indications.

  13. Consumer Driven Computer Game Design

    OpenAIRE

    Trappey, Charles

    2005-01-01

    The Critical Incident Techniques (CIT) is widely used to study customer satisfaction and dissatisfaction in the service industry. CIT provides questionnaire respondents with an open format to describe in their own words incidents that create lasting impressions. The purpose of this research is to develop a methodology for computer game design with the goal and intent of creating games that increase the consumer’s satisfaction through play. Too often game designers, either with or without inte...

  14. Target based drug design - a reality in virtual sphere.

    Science.gov (United States)

    Verma, Saroj; Prabhakar, Yenamandra S

    2015-01-01

    The target based drug design approaches are a series of computational procedures, including visualization tools, to support the decision systems of drug design/discovery process. In the essence of biological targets shaping the potential lead/drug molecules, this review presents a comprehensive position of different components of target based drug design which include target identification, protein modeling, molecular dynamics simulations, binding/catalytic sites identification, docking, virtual screening, fragment based strategies, substructure treatment of targets in tackling drug resistance, in silico ADMET, structural vaccinology, etc along with the key issues involved therein and some well investigated case studies. The concepts and working of these procedures are critically discussed to arouse interest and to advance the drug research.

  15. Ginger components as new leads for the design and development of novel multi-targeted anti-Alzheimer’s drugs: a computational investigation

    Directory of Open Access Journals (Sweden)

    Azam F

    2014-10-01

    Full Text Available Faizul Azam,1,2 Abdualrahman M Amer,1 Abdullah R Abulifa,1 Mustafa M Elzwawi1 1Faculty of Pharmacy, Misurata University, Misurata, Libya; 2Department of Pharmaceutical Chemistry, Nims Institute of Pharmacy, Nims University, Jaipur, Rajasthan, India Abstract: Ginger (Zingiber officinale, despite being a common dietary adjunct that contributes to the taste and flavor of foods, is well known to contain a number of potentially bioactive phytochemicals having valuable medicinal properties. Although recent studies have emphasized their benefits in Alzheimer’s disease, limited information is available on the possible mechanism by which it renders anti-Alzheimer activity. Therefore, the present study seeks to employ molecular docking studies to investigate the binding interactions between active ginger components and various anti-Alzheimer drug targets. Lamarckian genetic algorithm methodology was employed for docking of 12 ligands with 13 different target proteins using AutoDock 4.2 program. Docking protocol was validated by re-docking of all native co-crystallized ligands into their original binding cavities exhibiting a strong correlation coefficient value (r2=0.931 between experimentally reported and docking predicted activities. This value suggests that the approach could be a promising computational tool to aid optimization of lead compounds obtained from ginger. Analysis of binding energy, predicted inhibition constant, and hydrophobic/hydrophilic interactions of ligands with target receptors revealed acetylcholinesterase as most promising, while c-Jun N-terminal kinase was recognized as the least favorable anti-Alzheimer’s drug target. Common structural requirements include hydrogen bond donor/acceptor area, hydrophobic domain, carbon spacer, and distal hydrophobic domain flanked by hydrogen bond donor/acceptor moieties. In addition, drug-likeness score and molecular properties responsible for a good pharmacokinetic profile were calculated

  16. A computational analysis of the binding mode of closantel as inhibitor of the Onchocerca volvulus chitinase: insights on macrofilaricidal drug design

    Science.gov (United States)

    Segura-Cabrera, Aldo; Bocanegra-García, Virgilio; Lizarazo-Ortega, Cristian; Guo, Xianwu; Correa-Basurto, José; Rodríguez-Pérez, Mario A.

    2011-12-01

    Onchocerciasis is a leading cause of blindness with at least 37 million people infected and more than 120 million people at risk of contracting the disease; most (99%) of this population, threatened by infection, live in Africa. The drug of choice for mass treatment is the microfilaricidal Mectizan® (ivermectin); it does not kill the adult stages of the parasite at the standard dose which is a single annual dose aimed at disease control. However, multiple treatments a year with ivermectin have effects on adult worms. The discovery of new therapeutic targets and drugs directed towards the killing of the adult parasites are thus urgently needed. The chitinase of filarial nematodes is a new drug target due to its essential function in the metabolism and molting of the parasite. Closantel is a potent and specific inhibitor of chitinase of Onchocerca volvulus (OvCHT1) and other filarial chitinases. However, the binding mode and specificity of closantel towards OvCHT1 remain unknown. In the absence of a crystallographic structure of OvCHT1, we developed a homology model of OvCHT1 using the currently available X-ray structures of human chitinases as templates. Energy minimization and molecular dynamics (MD) simulation of the model led to a high quality of 3D structure of OvCHIT1. A flexible docking study using closantel as the ligand on the binding site of OvCHIT1 and human chitinases was performed and demonstrated the differences in the closantel binding mode between OvCHIT1 and human chitinase. Furthermore, molecular dynamics simulations and free-energy calculation were employed to determine and compare the detailed binding mode of closantel with OvCHT1 and the structure of human chitinase. This comparative study allowed identification of structural features and properties responsible for differences in the computationally predicted closantel binding modes. The homology model and the closantel binding mode reported herein might help guide the rational development of

  17. de novo computational enzyme design.

    Science.gov (United States)

    Zanghellini, Alexandre

    2014-10-01

    Recent advances in systems and synthetic biology as well as metabolic engineering are poised to transform industrial biotechnology by allowing us to design cell factories for the sustainable production of valuable fuels and chemicals. To deliver on their promises, such cell factories, as much as their brick-and-mortar counterparts, will require appropriate catalysts, especially for classes of reactions that are not known to be catalyzed by enzymes in natural organisms. A recently developed methodology, de novo computational enzyme design can be used to create enzymes catalyzing novel reactions. Here we review the different classes of chemical reactions for which active protein catalysts have been designed as well as the results of detailed biochemical and structural characterization studies. We also discuss how combining de novo computational enzyme design with more traditional protein engineering techniques can alleviate the shortcomings of state-of-the-art computational design techniques and create novel enzymes with catalytic proficiencies on par with natural enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Computer-aided system design

    Science.gov (United States)

    Walker, Carrie K.

    1991-01-01

    A technique has been developed for combining features of a systems architecture design and assessment tool and a software development tool. This technique reduces simulation development time and expands simulation detail. The Architecture Design and Assessment System (ADAS), developed at the Research Triangle Institute, is a set of computer-assisted engineering tools for the design and analysis of computer systems. The ADAS system is based on directed graph concepts and supports the synthesis and analysis of software algorithms mapped to candidate hardware implementations. Greater simulation detail is provided by the ADAS functional simulator. With the functional simulator, programs written in either Ada or C can be used to provide a detailed description of graph nodes. A Computer-Aided Software Engineering tool developed at the Charles Stark Draper Laboratory (CSDL CASE) automatically generates Ada or C code from engineering block diagram specifications designed with an interactive graphical interface. A technique to use the tools together has been developed, which further automates the design process.

  19. Computational design of rolling bearings

    CERN Document Server

    Nguyen-Schäfer, Hung

    2016-01-01

    This book comprehensively presents the computational design of rolling bearings dealing with many interdisciplinary difficult working fields. They encompass elastohydrodynamics (EHD), Hertzian contact theory, oil-film thickness in elastohydrodynamic lubrication (EHL), bearing dynamics, tribology of surface textures, fatigue failure mechanisms, fatigue lifetimes of rolling bearings and lubricating greases, Weibull distribution, rotor balancing, and airborne noises (NVH) in the rolling bearings. Furthermore, the readers are provided with hands-on essential formulas based on the up-to-date DIN ISO norms and helpful examples for computational design of rolling bearings. The topics are intended for undergraduate and graduate students in mechanical and material engineering, research scientists, and practicing engineers who want to understand the interactions between these working fields and to know how to design the rolling bearings for automotive industry and many other industries.

  20. 4D-QSAR: Perspectives in Drug Design

    Directory of Open Access Journals (Sweden)

    Carolina H. Andrade

    2010-05-01

    Full Text Available Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. The quantitative structure–activity relationship (QSAR formalisms are among the most important strategies that can be applied for the successful design new molecules. This review provides a comprehensive review on the evolution and current status of 4D-QSAR, highlighting present challenges and new opportunities in drug design.

  1. Digital computer structure and design

    CERN Document Server

    Townsend, R

    2014-01-01

    Digital Computer Structure and Design, Second Edition discusses switching theory, counters, sequential circuits, number representation, and arithmetic functions The book also describes computer memories, the processor, data flow system of the processor, the processor control system, and the input-output system. Switching theory, which is purely a mathematical concept, centers on the properties of interconnected networks of ""gates."" The theory deals with binary functions of 1 and 0 which can change instantaneously from one to the other without intermediate values. The binary number system is

  2. "9th Annual Congress on Drug Formulation & Drug Design"

    OpenAIRE

    Monty Karl

    2017-01-01

    Conference Series has been instrumental in conducting international meetings for seven years, and very excited to expand Europe, America and Asia Pacific continents. Previous meetings were held in major cities like Belgium, Tokyo, Madrid, with success the meetings again scheduled in three continents. It’s time to announce 9th Annual Congress on Drug Formulation & Drug Design October 19-21, 2017 Seoul, South Korea . Drug Formulation 2017 is a 3-day event offering the Exhibition, at venue to sh...

  3. Multiscale Modeling in the Clinic: Drug Design and Development

    Energy Technology Data Exchange (ETDEWEB)

    Clancy, Colleen E.; An, Gary; Cannon, William R.; Liu, Yaling; May, Elebeoba E.; Ortoleva, Peter; Popel, Aleksander S.; Sluka, James P.; Su, Jing; Vicini, Paolo; Zhou, Xiaobo; Eckmann, David M.

    2016-02-17

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.

  4. Editorial: in silico drug design and medicinal chemistry).

    Science.gov (United States)

    Singla, Rajeev K

    2015-01-01

    Medicinal chemistry is not limited to molecules, their structures and design but also highly cohesive to pharmacological activities. The potency of a molecule varies by its structure. Hence structural activity relationship is the sub-branch which deals with the estimation of ability of a molecule in depicting any pharmacological activity. In silico drug design is a novel technique which is employed in designing a molecule by using computer aided software’s and bringing a superior and potent molecule. In recent years, in silico drug design has been merged with medicinal chemistry especially by the techniques like ligand based strategy to isolate the required structures. By such strategic techniques, there are high chances of delivering high throughput screening which involves of screening large number of molecules in a very less time. Involvement of such techniques would be a boon for development of new drug entity as it can aid in development of newer, safe, effective and potent drug molecules. Hence, the present issue is aimed to emphasize the cohesion between in silico drug design and it significance in medicinal chemistry. The articles which would be published will mainly focus on the role of in silico drug design techniques in the development of molecules to target various disease and disorders. Molecules can from natural/ synthetic/semi synthetic origin. Articles will be a treasure box consisting of employment of computational methods for unprecedented molecules. The issue will be sure an endorsement for international readership and researchers.

  5. Computer-Aided Drug Discovery in Plant Pathology.

    Science.gov (United States)

    Shanmugam, Gnanendra; Jeon, Junhyun

    2017-12-01

    Control of plant diseases is largely dependent on use of agrochemicals. However, there are widening gaps between our knowledge on plant diseases gained from genetic/mechanistic studies and rapid translation of the knowledge into target-oriented development of effective agrochemicals. Here we propose that the time is ripe for computer-aided drug discovery/design (CADD) in molecular plant pathology. CADD has played a pivotal role in development of medically important molecules over the last three decades. Now, explosive increase in information on genome sequences and three dimensional structures of biological molecules, in combination with advances in computational and informational technologies, opens up exciting possibilities for application of CADD in discovery and development of agrochemicals. In this review, we outline two categories of the drug discovery strategies: structure- and ligand-based CADD, and relevant computational approaches that are being employed in modern drug discovery. In order to help readers to dive into CADD, we explain concepts of homology modelling, molecular docking, virtual screening, and de novo ligand design in structure-based CADD, and pharmacophore modelling, ligand-based virtual screening, quantitative structure activity relationship modelling and de novo ligand design for ligand-based CADD. We also provide the important resources available to carry out CADD. Finally, we present a case study showing how CADD approach can be implemented in reality for identification of potent chemical compounds against the important plant pathogens, Pseudomonas syringae and Colletotrichum gloeosporioides .

  6. Computational prediction of drug-drug interactions based on drugs functional similarities.

    Science.gov (United States)

    Ferdousi, Reza; Safdari, Reza; Omidi, Yadollah

    2017-06-01

    Therapeutic activities of drugs are often influenced by co-administration of drugs that may cause inevitable drug-drug interactions (DDIs) and inadvertent side effects. Prediction and identification of DDIs are extremely vital for the patient safety and success of treatment modalities. A number of computational methods have been employed for the prediction of DDIs based on drugs structures and/or functions. Here, we report on a computational method for DDIs prediction based on functional similarity of drugs. The model was set based on key biological elements including carriers, transporters, enzymes and targets (CTET). The model was applied for 2189 approved drugs. For each drug, all the associated CTETs were collected, and the corresponding binary vectors were constructed to determine the DDIs. Various similarity measures were conducted to detect DDIs. Of the examined similarity methods, the inner product-based similarity measures (IPSMs) were found to provide improved prediction values. Altogether, 2,394,766 potential drug pairs interactions were studied. The model was able to predict over 250,000 unknown potential DDIs. Upon our findings, we propose the current method as a robust, yet simple and fast, universal in silico approach for identification of DDIs. We envision that this proposed method can be used as a practical technique for the detection of possible DDIs based on the functional similarities of drugs. Copyright © 2017. Published by Elsevier Inc.

  7. Understanding and designing computer networks

    CERN Document Server

    King, Graham

    1995-01-01

    Understanding and Designing Computer Networks considers the ubiquitous nature of data networks, with particular reference to internetworking and the efficient management of all aspects of networked integrated data systems. In addition it looks at the next phase of networking developments; efficiency and security are covered in the sections dealing with data compression and data encryption; and future examples of network operations, such as network parallelism, are introduced.A comprehensive case study is used throughout the text to apply and illustrate new techniques and concepts as th

  8. Achievements and Challenges in Computational Protein Design.

    Science.gov (United States)

    Samish, Ilan

    2017-01-01

    Computational protein design (CPD), a yet evolving field, includes computer-aided engineering for partial or full de novo designs of proteins of interest. Designs are defined by a requested structure, function, or working environment. This chapter describes the birth and maturation of the field by presenting 101 CPD examples in a chronological order emphasizing achievements and pending challenges. Integrating these aspects presents the plethora of CPD approaches with the hope of providing a "CPD 101". These reflect on the broader structural bioinformatics and computational biophysics field and include: (1) integration of knowledge-based and energy-based methods, (2) hierarchical designated approach towards local, regional, and global motifs and the integration of high- and low-resolution design schemes that fit each such region, (3) systematic differential approaches towards different protein regions, (4) identification of key hot-spot residues and the relative effect of remote regions, (5) assessment of shape-complementarity, electrostatics and solvation effects, (6) integration of thermal plasticity and functional dynamics, (7) negative design, (8) systematic integration of experimental approaches, (9) objective cross-assessment of methods, and (10) successful ranking of potential designs. Future challenges also include dissemination of CPD software to the general use of life-sciences researchers and the emphasis of success within an in vivo milieu. CPD increases our understanding of protein structure and function and the relationships between the two along with the application of such know-how for the benefit of mankind. Applied aspects range from biological drugs, via healthier and tastier food products to nanotechnology and environmentally friendly enzymes replacing toxic chemicals utilized in the industry.

  9. Thermodynamic Studies for Drug Design and Screening

    Science.gov (United States)

    Garbett, Nichola C.; Chaires, Jonathan B.

    2012-01-01

    Introduction A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. Areas covered This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 – 2011 using the Science Citation Index and PUBMED and the keywords listed below. Expert opinion The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically-driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development towards an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. PMID:22458502

  10. Thermodynamic studies for drug design and screening.

    Science.gov (United States)

    Garbett, Nichola C; Chaires, Jonathan B

    2012-04-01

    A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 - 2011 using the Science Citation Index and PUBMED and the keywords listed below. The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development toward an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in the design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. © 2012 Informa UK, Ltd.

  11. Comprehensive computational design of ordered peptide macrocycles

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram K.; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fatima; Rettie, Stephan A.; Kim, David E.; Silva, Daniel A.; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

    2017-12-14

    Mixed chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to-date, but there is currently no way to systematically search through the structural space spanned by such compounds for new drug candidates. Natural proteins do not provide a useful guide: peptide macrocycles lack regular secondary structures and hydrophobic cores and have different backbone torsional constraints. Hence the development of new peptide macrocycles has been approached by modifying natural products or using library selection methods; the former is limited by the small number of known structures, and the latter by the limited size and diversity accessible through library-based methods. To overcome these limitations, here we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L and D amino acids. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. We synthesize and characterize by NMR twelve 7-10 residue macrocycles, 9 of which have structures very close to the design models in solution. NMR structures of three 11-14 residue bicyclic designs are also very close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide based macrocycles unparalleled for other molecular systems, and vastly increase the available starting scaffolds for both rational drug design and library selection methods.

  12. Metabolism of designer drugs of abuse.

    Science.gov (United States)

    Staack, Roland F; Maurer, Hans H

    2005-06-01

    Abuse of designer drugs is widespread among young people, especially in the so-called "dance club scene" or "rave scene", worldwide. Severe and even fatal poisonings have been attributed to the consumption of such drugs of abuse. However, in contrast to new medicaments, which are extensively studied in controlled clinical studies concerning metabolism, including cytochrome P450 isoenzyme differentiation, and further pharmacokinetics, designer drugs are consumed without any safety testing. This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA) and 4-methylthioamphetamine (4-MTA), were taken into consideration as new "classical" amphetamine-derived designer drugs. Furthermore, N-benzylpiperazine (BZP), 1-(3, 4-methylenedioxybenzyl)piperazine (MDBP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP) were taken into consideration as derivatives of the class of piperazine-derived designer drugs, as well as alpha-pyr-rolidinopropiophenone (PPP), 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), 3', 4'-methylenedioxy-alpha-pyrrolidino-propiophenone (MDPPP), 4'-methyl-alpha-pyrrolidinopropiophenone (MPPP), and 4'-methyl-alpha-pyrrolidinoexanophenone (MPHP) as derivatives of the class of alpha-pyrrolidinophenone-derived designer drugs. Papers describing identification of in vivo or in vitro human or animal metabolites and cytochrome P450 isoenzyme dependent metabolism have been considered and summarized.

  13. Designer Drug Confusion: A Focus on MDMA.

    Science.gov (United States)

    Beck, Jerome; Morgan, Patricia A.

    1986-01-01

    Discusses the competing definitions and issues surrounding various designer drugs, primarily 3, 4-methylenedioxy-methamphetamine (MDMA). Offers a rationale for why interest in MDMA, which possesses both stimulant and psychedelic properties, will continue to grow despite the drug's recent illegality and increasing evidence of neurotoxicity.…

  14. Computer Applications in the Design Process.

    Science.gov (United States)

    Winchip, Susan

    Computer Assisted Design (CAD) and Computer Assisted Manufacturing (CAM) are emerging technologies now being used in home economics and interior design applications. A microcomputer in a computer network system is capable of executing computer graphic functions such as three-dimensional modeling, as well as utilizing office automation packages to…

  15. Smarter Drugs: How Protein Crystallography Revolutionizes Drug Design

    International Nuclear Information System (INIS)

    Smith, Clyde

    2005-01-01

    According to Smith, protein crystallography allows scientists to design drugs in a much more efficient way than the standard methods traditionally used by large drug companies, which can cost close to a billion dollars and take 10 to 15 years. 'A lot of the work can be compressed down,' Smith said. Protein crystallography enables researchers to learn the structure of molecules involved in disease and health. Seeing the loops, folds and placement of atoms in anything from a virus to a healthy cell membrane gives important information about how these things work - and how to encourage, sidestep or stop their functions. Drug design can be much faster when the relationship between structure and function tells you what area of a molecule to target. Smith will use a timeline to illustrate the traditional methods of drug development and the new ways it can be done now. 'It is very exciting work. There have been some failures, but many successes too.' A new drug to combat the flu was developed in a year or so. Smith will tell us how. He will also highlight drugs developed to combat HIV, Tuberculosis, hypertension and Anthrax.

  16. LEGO-inspired drug design

    DEFF Research Database (Denmark)

    Thanh Tung, Truong; Dao, Trong Tuan; Grifell Junyent, Marta

    2018-01-01

    The fungal plasma membrane H+-ATPase (Pma1p) is a potential target for the discovery of new antifungal agents. Surprisingly, no structure-activity relationship studies for small molecules targeting Pma1p have been reported. Herein, we disclose a LEGO-inspired fragment assembly strategy for design...

  17. Intratumor heterogeneity alters most effective drugs in designed combinations.

    Science.gov (United States)

    Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A

    2014-07-22

    The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.

  18. Designs 2002 further computational and constructive design theory

    CERN Document Server

    2003-01-01

    This volume is a sequel to the 1996 compilation, Computational and Constructive Design Theory. It contains research papers and surveys of recent research work on two closely related aspects of the study of combinatorial designs: design construction and computer-aided study of designs. Audience: This volume is suitable for researchers in the theory of combinatorial designs

  19. Rational design of liposomal drug delivery systems, a review: Combined experimental and computational studies of lipid membranes, liposomes and their PEGylation

    Czech Academy of Sciences Publication Activity Database

    Bunker, A.; Magarkar, Aniket; Viitala, T.

    2016-01-01

    Roč. 1858, č. 10 (2016), s. 2334-2352 ISSN 0005-2736 Institutional support: RVO:61388963 Keywords : nanomedicine * liposome * drug delivery * molecular dynamics simulation * label-free analytics * PEGylation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.498, year: 2016

  20. Comprehensive computational design of ordered peptide macrocycles

    Science.gov (United States)

    Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fátima; Rettie, Stephen A.; Kim, David E.; Silva, Daniel-Adriano; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

    2018-01-01

    Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with L-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L- and D-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods. PMID:29242347

  1. Molecular Rift: Virtual Reality for Drug Designers.

    Science.gov (United States)

    Norrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Boström, Jonas

    2015-11-23

    Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate physical presence in the real world--a virtual reality. This is relevant to drug discovery since molecular models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Molecular Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for standard input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Molecular Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chemistry and education. Molecular Rift is open source and can be downloaded from GitHub.

  2. Biomimetic design processes in architecture: morphogenetic and evolutionary computational design

    International Nuclear Information System (INIS)

    Menges, Achim

    2012-01-01

    Design computation has profound impact on architectural design methods. This paper explains how computational design enables the development of biomimetic design processes specific to architecture, and how they need to be significantly different from established biomimetic processes in engineering disciplines. The paper first explains the fundamental difference between computer-aided and computational design in architecture, as the understanding of this distinction is of critical importance for the research presented. Thereafter, the conceptual relation and possible transfer of principles from natural morphogenesis to design computation are introduced and the related developments of generative, feature-based, constraint-based, process-based and feedback-based computational design methods are presented. This morphogenetic design research is then related to exploratory evolutionary computation, followed by the presentation of two case studies focusing on the exemplary development of spatial envelope morphologies and urban block morphologies. (paper)

  3. Computational Design Tools for Integrated Design

    DEFF Research Database (Denmark)

    Holst, Malene Kirstine; Kirkegaard, Poul Henning

    2010-01-01

    In an architectural conceptual sketching process, where an architect is working with the initial ideas for a design, the process is characterized by three phases: sketching, evaluation and modification. Basically the architect needs to address three areas in the conceptual sketching phase......: aesthetical, functional and technical requirements. The aim of the present paper is to address the problem of a vague or not existing link between digital conceptual design tools used by architects and designers and engineering analysis and simulation tools. Based on an analysis of the architectural design...... process different digital design methods are related to tasks in an integrated design process....

  4. Targeted proteins for diabetes drug design

    Science.gov (United States)

    Doan Trang Nguyen, Ngoc; Thi Le, Ly

    2012-03-01

    Type 2 diabetes mellitus is a common metabolism disorder characterized by high glucose in the bloodstream, especially in the case of insulin resistance and relative insulin deficiency. Nowadays, it is very common in middle-aged people and involves such dangerous symptoms as increasing risk of stroke, obesity and heart failure. In Vietnam, besides the common treatment of insulin injection, some herbal medication is used but no unified optimum remedy for the disease yet exists and there is no production of antidiabetic drugs in the domestic market yet. In the development of nanomedicine at the present time, drug design is considered as an innovative tool for researchers to study the mechanisms of diseases at the molecular level. The aim of this article is to review some common protein targets involved in type 2 diabetes, offering a new idea for designing new drug candidates to produce antidiabetic drugs against type 2 diabetes for Vietnamese people.

  5. Targeted proteins for diabetes drug design

    International Nuclear Information System (INIS)

    Trang Nguyen, Ngoc Doan; Le, Ly Thi

    2012-01-01

    Type 2 diabetes mellitus is a common metabolism disorder characterized by high glucose in the bloodstream, especially in the case of insulin resistance and relative insulin deficiency. Nowadays, it is very common in middle-aged people and involves such dangerous symptoms as increasing risk of stroke, obesity and heart failure. In Vietnam, besides the common treatment of insulin injection, some herbal medication is used but no unified optimum remedy for the disease yet exists and there is no production of antidiabetic drugs in the domestic market yet. In the development of nanomedicine at the present time, drug design is considered as an innovative tool for researchers to study the mechanisms of diseases at the molecular level. The aim of this article is to review some common protein targets involved in type 2 diabetes, offering a new idea for designing new drug candidates to produce antidiabetic drugs against type 2 diabetes for Vietnamese people. (review)

  6. Computational Support for Creative Design

    KAUST Repository

    Liu, Han

    2015-12-09

    rooms, and fabrication considerations (i.e., economic construction cost). Secondly, we introduce replaceable substructures as arrangements of shape components that can be interchanged while ensuring boundary consistency. Based on the shape graphs that encode the structures of input models, we propose new automatic operations to discover replaceable substructures across models or within a model. We enforce a pair of subgraphs matching along their boundaries so that switching two subgraphs results in topological variations. Thirdly, we develop an interactive system that supports a freeform design by interpreting user sketches. 3D contents can be extracted from input strokes with or without user annotations. Our system accepts user strokes, analyzes their contacts and vanishing directions with respect to an anchored image, and projects 2D strokes to 3D space via a multi- stage optimization on spatial canvas selection. We demonstrate the computational approaches on a range of example models and design studies.

  7. Advanced topics in security computer system design

    International Nuclear Information System (INIS)

    Stachniak, D.E.; Lamb, W.R.

    1989-01-01

    The capability, performance, and speed of contemporary computer processors, plus the associated performance capability of the operating systems accommodating the processors, have enormously expanded the scope of possibilities for designers of nuclear power plant security computer systems. This paper addresses the choices that could be made by a designer of security computer systems working with contemporary computers and describes the improvement in functionality of contemporary security computer systems based on an optimally chosen design. Primary initial considerations concern the selection of (a) the computer hardware and (b) the operating system. Considerations for hardware selection concern processor and memory word length, memory capacity, and numerous processor features

  8. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

    Science.gov (United States)

    2010-04-01

    ...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Timing of requests for orphan-drug designation..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan...

  9. Interactive design computation : A case study on quantum design paradigm

    NARCIS (Netherlands)

    Feng, H.

    2013-01-01

    The ever-increasing complexity of design processes fosters novel design computation models to be employed in architectural research and design in order to facilitate accurate data processing and refined decision making. These computation models have enabled designers to work with complex geometry

  10. Novel opportunities for computational biology and sociology in drug discovery☆

    Science.gov (United States)

    Yao, Lixia; Evans, James A.; Rzhetsky, Andrey

    2013-01-01

    Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development, explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy–industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies. PMID:20349528

  11. Novel opportunities for computational biology and sociology in drug discovery

    Science.gov (United States)

    Yao, Lixia

    2009-01-01

    Drug discovery today is impossible without sophisticated modeling and computation. In this review we touch on previous advances in computational biology and by tracing the steps involved in pharmaceutical development, we explore a range of novel, high value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry ties for scientific and human benefit. Attention to these opportunities could promise punctuated advance, and will complement the well-established computational work on which drug discovery currently relies. PMID:19674801

  12. Computational Intelligence Techniques for New Product Design

    CERN Document Server

    Chan, Kit Yan; Dillon, Tharam S

    2012-01-01

    Applying computational intelligence for product design is a fast-growing and promising research area in computer sciences and industrial engineering. However, there is currently a lack of books, which discuss this research area. This book discusses a wide range of computational intelligence techniques for implementation on product design. It covers common issues on product design from identification of customer requirements in product design, determination of importance of customer requirements, determination of optimal design attributes, relating design attributes and customer satisfaction, integration of marketing aspects into product design, affective product design, to quality control of new products. Approaches for refinement of computational intelligence are discussed, in order to address different issues on product design. Cases studies of product design in terms of development of real-world new products are included, in order to illustrate the design procedures, as well as the effectiveness of the com...

  13. DrugSig: A resource for computational drug repositioning utilizing gene expression signatures.

    Directory of Open Access Journals (Sweden)

    Hongyu Wu

    Full Text Available Computational drug repositioning has been proved as an effective approach to develop new drug uses. However, currently existing strategies strongly rely on drug response gene signatures which scattered in separated or individual experimental data, and resulted in low efficient outputs. So, a fully drug response gene signatures database will be very helpful to these methods. We collected drug response microarray data and annotated related drug and targets information from public databases and scientific literature. By selecting top 500 up-regulated and down-regulated genes as drug signatures, we manually established the DrugSig database. Currently DrugSig contains more than 1300 drugs, 7000 microarray and 800 targets. Moreover, we developed the signature based and target based functions to aid drug repositioning. The constructed database can serve as a resource to quicken computational drug repositioning. Database URL: http://biotechlab.fudan.edu.cn/database/drugsig/.

  14. Defining Patient Centric Pharmaceutical Drug Product Design.

    Science.gov (United States)

    Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A

    2016-09-01

    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved.

  15. MPD3: a useful medicinal plants database for drug designing.

    Science.gov (United States)

    Mumtaz, Arooj; Ashfaq, Usman Ali; Ul Qamar, Muhammad Tahir; Anwar, Farooq; Gulzar, Faisal; Ali, Muhammad Amjad; Saari, Nazamid; Pervez, Muhammad Tariq

    2017-06-01

    Medicinal plants are the main natural pools for the discovery and development of new drugs. In the modern era of computer-aided drug designing (CADD), there is need of prompt efforts to design and construct useful database management system that allows proper data storage, retrieval and management with user-friendly interface. An inclusive database having information about classification, activity and ready-to-dock library of medicinal plant's phytochemicals is therefore required to assist the researchers in the field of CADD. The present work was designed to merge activities of phytochemicals from medicinal plants, their targets and literature references into a single comprehensive database named as Medicinal Plants Database for Drug Designing (MPD3). The newly designed online and downloadable MPD3 contains information about more than 5000 phytochemicals from around 1000 medicinal plants with 80 different activities, more than 900 literature references and 200 plus targets. The designed database is deemed to be very useful for the researchers who are engaged in medicinal plants research, CADD and drug discovery/development with ease of operation and increased efficiency. The designed MPD3 is a comprehensive database which provides most of the information related to the medicinal plants at a single platform. MPD3 is freely available at: http://bioinform.info .

  16. Designer drugs: how dangerous are they?

    NARCIS (Netherlands)

    Reneman, L.

    2003-01-01

    Of the designer drugs, the amphetamine analogues are the most popular and extensively studied, ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in particular. They are used recreationally with increasing popularity despite animal studies showing neurotoxic effects to serotonin (5-HT) and/or

  17. Web-based services for drug design and discovery.

    Science.gov (United States)

    Frey, Jeremy G; Bird, Colin L

    2011-09-01

    Reviews of the development of drug discovery through the 20(th) century recognised the importance of chemistry and increasingly bioinformatics, but had relatively little to say about the importance of computing and networked computing in particular. However, the design and discovery of new drugs is arguably the most significant single application of bioinformatics and cheminformatics to have benefitted from the increases in the range and power of the computational techniques since the emergence of the World Wide Web, commonly now referred to as simply 'the Web'. Web services have enabled researchers to access shared resources and to deploy standardized calculations in their search for new drugs. This article first considers the fundamental principles of Web services and workflows, and then explores the facilities and resources that have evolved to meet the specific needs of chem- and bio-informatics. This strategy leads to a more detailed examination of the basic components that characterise molecules and the essential predictive techniques, followed by a discussion of the emerging networked services that transcend the basic provisions, and the growing trend towards embracing modern techniques, in particular the Semantic Web. In the opinion of the authors, the issues that require community action are: increasing the amount of chemical data available for open access; validating the data as provided; and developing more efficient links between the worlds of cheminformatics and bioinformatics. The goal is to create ever better drug design services.

  18. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

    Directory of Open Access Journals (Sweden)

    Apurv Patel

    2016-01-01

    Full Text Available The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients.

  19. New design methods for computer aided architecturald design methodology teaching

    NARCIS (Netherlands)

    Achten, H.H.

    2003-01-01

    Architects and architectural students are exploring new ways of design using Computer Aided Architectural Design software. This exploration is seldom backed up from a design methodological viewpoint. In this paper, a design methodological framework for reflection on innovate design processes by

  20. Modeling chemical reactions for drug design.

    Science.gov (United States)

    Gasteiger, Johann

    2007-01-01

    Chemical reactions are involved at many stages of the drug design process. This starts with the analysis of biochemical pathways that are controlled by enzymes that might be downregulated in certain diseases. In the lead discovery and lead optimization process compounds have to be synthesized in order to test them for their biological activity. And finally, the metabolism of a drug has to be established. A better understanding of chemical reactions could strongly help in making the drug design process more efficient. We have developed methods for quantifying the concepts an organic chemist is using in rationalizing reaction mechanisms. These methods allow a comprehensive modeling of chemical reactivity and thus are applicable to a wide variety of chemical reactions, from gas phase reactions to biochemical pathways. They are empirical in nature and therefore allow the rapid processing of large sets of structures and reactions. We will show here how methods have been developed for the prediction of acidity values and of the regioselectivity in organic reactions, for designing the synthesis of organic molecules and of combinatorial libraries, and for furthering our understanding of enzyme-catalyzed reactions and of the metabolism of drugs.

  1. Designing the next generation (fifth generation computers)

    International Nuclear Information System (INIS)

    Wallich, P.

    1983-01-01

    A description is given of the designs necessary to develop fifth generation computers. An analysis is offered of problems and developments in parallelism, VLSI, artificial intelligence, knowledge engineering and natural language processing. Software developments are outlined including logic programming, object-oriented programming and exploratory programming. Computer architecture is detailed including concurrent computer architecture

  2. Office ergonomics: deficiencies in computer workstation design.

    Science.gov (United States)

    Shikdar, Ashraf A; Al-Kindi, Mahmoud A

    2007-01-01

    The objective of this research was to study and identify ergonomic deficiencies in computer workstation design in typical offices. Physical measurements and a questionnaire were used to study 40 workstations. Major ergonomic deficiencies were found in physical design and layout of the workstations, employee postures, work practices, and training. The consequences in terms of user health and other problems were significant. Forty-five percent of the employees used nonadjustable chairs, 48% of computers faced windows, 90% of the employees used computers more than 4 hrs/day, 45% of the employees adopted bent and unsupported back postures, and 20% used office tables for computers. Major problems reported were eyestrain (58%), shoulder pain (45%), back pain (43%), arm pain (35%), wrist pain (30%), and neck pain (30%). These results indicated serious ergonomic deficiencies in office computer workstation design, layout, and usage. Strategies to reduce or eliminate ergonomic deficiencies in computer workstation design were suggested.

  3. Algorithmic Mechanism Design of Evolutionary Computation.

    Science.gov (United States)

    Pei, Yan

    2015-01-01

    We consider algorithmic design, enhancement, and improvement of evolutionary computation as a mechanism design problem. All individuals or several groups of individuals can be considered as self-interested agents. The individuals in evolutionary computation can manipulate parameter settings and operations by satisfying their own preferences, which are defined by an evolutionary computation algorithm designer, rather than by following a fixed algorithm rule. Evolutionary computation algorithm designers or self-adaptive methods should construct proper rules and mechanisms for all agents (individuals) to conduct their evolution behaviour correctly in order to definitely achieve the desired and preset objective(s). As a case study, we propose a formal framework on parameter setting, strategy selection, and algorithmic design of evolutionary computation by considering the Nash strategy equilibrium of a mechanism design in the search process. The evaluation results present the efficiency of the framework. This primary principle can be implemented in any evolutionary computation algorithm that needs to consider strategy selection issues in its optimization process. The final objective of our work is to solve evolutionary computation design as an algorithmic mechanism design problem and establish its fundamental aspect by taking this perspective. This paper is the first step towards achieving this objective by implementing a strategy equilibrium solution (such as Nash equilibrium) in evolutionary computation algorithm.

  4. The evolution of drug design at Merck Research Laboratories.

    Science.gov (United States)

    Brown, Frank K; Sherer, Edward C; Johnson, Scott A; Holloway, M Katharine; Sherborne, Bradley S

    2017-03-01

    On October 5, 1981, Fortune magazine published a cover article entitled the "Next Industrial Revolution: Designing Drugs by Computer at Merck". With a 40+ year investment, we have been in the drug design business longer than most. During its history, the Merck drug design group has had several names, but it has always been in the "design" business, with the ultimate goal to provide an actionable hypothesis that could be tested experimentally. Often the result was a small molecule but it could just as easily be a peptide, biologic, predictive model, reaction, process, etc. To this end, the concept of design is now front and center in all aspects of discovery, safety assessment and early clinical development. At present, the Merck design group includes computational chemistry, protein structure determination, and cheminformatics. By bringing these groups together under one umbrella, we were able to align activities and capabilities across multiple research sites and departments. This alignment from 2010 to 2016 resulted in an 80% expansion in the size of the department, reflecting the increase in impact due to a significant emphasis across the organization to "design first" along the entire drug discovery path from lead identification (LID) to first in human (FIH) dosing. One of the major advantages of this alignment has been the ability to access all of the data and create an adaptive approach to the overall LID to FIH pathway for any modality, significantly increasing the quality of candidates and their probability of success. In this perspective, we will discuss how we crafted a new strategy, defined the appropriate phenotype for group members, developed the right skillsets, and identified metrics for success in order to drive continuous improvement. We will not focus on the tactical implementation, only giving specific examples as appropriate.

  5. The evolution of drug design at Merck Research Laboratories

    Science.gov (United States)

    Brown, Frank K.; Sherer, Edward C.; Johnson, Scott A.; Holloway, M. Katharine; Sherborne, Bradley S.

    2017-03-01

    On October 5, 1981, Fortune magazine published a cover article entitled the "Next Industrial Revolution: Designing Drugs by Computer at Merck". With a 40+ year investment, we have been in the drug design business longer than most. During its history, the Merck drug design group has had several names, but it has always been in the "design" business, with the ultimate goal to provide an actionable hypothesis that could be tested experimentally. Often the result was a small molecule but it could just as easily be a peptide, biologic, predictive model, reaction, process, etc. To this end, the concept of design is now front and center in all aspects of discovery, safety assessment and early clinical development. At present, the Merck design group includes computational chemistry, protein structure determination, and cheminformatics. By bringing these groups together under one umbrella, we were able to align activities and capabilities across multiple research sites and departments. This alignment from 2010 to 2016 resulted in an 80% expansion in the size of the department, reflecting the increase in impact due to a significant emphasis across the organization to "design first" along the entire drug discovery path from lead identification (LID) to first in human (FIH) dosing. One of the major advantages of this alignment has been the ability to access all of the data and create an adaptive approach to the overall LID to FIH pathway for any modality, significantly increasing the quality of candidates and their probability of success. In this perspective, we will discuss how we crafted a new strategy, defined the appropriate phenotype for group members, developed the right skillsets, and identified metrics for success in order to drive continuous improvement. We will not focus on the tactical implementation, only giving specific examples as appropriate.

  6. Integrated computer aided design simulation and manufacture

    OpenAIRE

    Diko, Faek

    1989-01-01

    Computer Aided Design (CAD) and Computer Aided Manufacture (CAM) have been investigated and developed since twenty years as standalone systems. A large number of very powerful but independent packages have been developed for Computer Aided Design,Aanlysis and Manufacture. However, in most cases these packages have poor facility for communicating with other packages. Recently attempts have been made to develop integrated CAD/CAM systems and many software companies a...

  7. The impact of pharmacophore modeling in drug design.

    Science.gov (United States)

    Guner, Osman F

    2005-07-01

    With the reliable use of computer simulations in scientific research, it is possible to achieve significant increases in productivity as well as a reduction in research costs compared with experimental approaches. For example, computer-simulation can substantially enchance productivity by focusing the scientist to better, more informed choices, while also driving the 'fail-early' concept to result in a significant reduction in cost. Pharmacophore modeling is a reliable computer-aided design tool used in the discovery of new classes of compounds for a given therapeutic category. This commentary will briefly review the benefits and applications of this technology in drug discovery and design, and will also highlight its historical evolution. The two most commonly used approaches for pharmacophore model development will be discussed, and several examples of how this technology was successfully applied to identify new potent leads will be provided. The article concludes with a brief outline of the controversial issue of patentability of pharmacophore models.

  8. Computers as components principles of embedded computing system design

    CERN Document Server

    Wolf, Marilyn

    2012-01-01

    Computers as Components: Principles of Embedded Computing System Design, 3e, presents essential knowledge on embedded systems technology and techniques. Updated for today's embedded systems design methods, this edition features new examples including digital signal processing, multimedia, and cyber-physical systems. Author Marilyn Wolf covers the latest processors from Texas Instruments, ARM, and Microchip Technology plus software, operating systems, networks, consumer devices, and more. Like the previous editions, this textbook: Uses real processors to demonstrate both technology and tec

  9. Virtual drug discovery: beyond computational chemistry?

    Science.gov (United States)

    Gilardoni, Francois; Arvanites, Anthony C

    2010-02-01

    This editorial looks at how a fully integrated structure that performs all aspects in the drug discovery process, under one company, is slowly disappearing. The steps in the drug discovery paradigm have been slowly increasing toward virtuality or outsourcing at various phases of product development in a company's candidate pipeline. Each step in the process, such as target identification and validation and medicinal chemistry, can be managed by scientific teams within a 'virtual' company. Pharmaceutical companies to biotechnology start-ups have been quick in adopting this new research and development business strategy in order to gain flexibility, access the best technologies and technical expertise, and decrease product developmental costs. In today's financial climate, the term virtual drug discovery has an organizational meaning. It represents the next evolutionary step in outsourcing drug development.

  10. A computational approach to finding novel targets for existing drugs.

    Directory of Open Access Journals (Sweden)

    Yvonne Y Li

    2011-09-01

    Full Text Available Repositioning existing drugs for new therapeutic uses is an efficient approach to drug discovery. We have developed a computational drug repositioning pipeline to perform large-scale molecular docking of small molecule drugs against protein drug targets, in order to map the drug-target interaction space and find novel interactions. Our method emphasizes removing false positive interaction predictions using criteria from known interaction docking, consensus scoring, and specificity. In all, our database contains 252 human protein drug targets that we classify as reliable-for-docking as well as 4621 approved and experimental small molecule drugs from DrugBank. These were cross-docked, then filtered through stringent scoring criteria to select top drug-target interactions. In particular, we used MAPK14 and the kinase inhibitor BIM-8 as examples where our stringent thresholds enriched the predicted drug-target interactions with known interactions up to 20 times compared to standard score thresholds. We validated nilotinib as a potent MAPK14 inhibitor in vitro (IC50 40 nM, suggesting a potential use for this drug in treating inflammatory diseases. The published literature indicated experimental evidence for 31 of the top predicted interactions, highlighting the promising nature of our approach. Novel interactions discovered may lead to the drug being repositioned as a therapeutic treatment for its off-target's associated disease, added insight into the drug's mechanism of action, and added insight into the drug's side effects.

  11. Computational Design Modelling : Proceedings of the Design Modelling Symposium

    CERN Document Server

    Kilian, Axel; Palz, Norbert; Scheurer, Fabian

    2012-01-01

    This book publishes the peer-reviewed proceeding of the third Design Modeling Symposium Berlin . The conference constitutes a platform for dialogue on experimental practice and research within the field of computationally informed architectural design. More than 60 leading experts the computational processes within the field of computationally informed architectural design to develop a broader and less exotic building practice that bears more subtle but powerful traces of the complex tool set and approaches we have developed and studied over recent years. The outcome are new strategies for a reasonable and innovative implementation of digital potential in truly innovative and radical design guided by both responsibility towards processes and the consequences they initiate.

  12. Designing with computers at Lawrence Berkeley Laboratory

    International Nuclear Information System (INIS)

    Colonas, J.S.

    1974-10-01

    The application of digital computers to the solution of engineering problems relating to accelerator design was explored. The existing computer hardware and software available for direct communication between the engineer and the computer are described, and some examples of useful programs are outlined, showing the ease of their use and the method of communication between machine and designer. An effort is made to convince engineers that they can communicate with the computer in ordinary English and mathematics, rather than in intermediate artificial languages. (U.S.)

  13. Optical Design Using Small Dedicated Computers

    Science.gov (United States)

    Sinclair, Douglas C.

    1980-09-01

    Since the time of the 1975 International Lens Design Conference, we have developed a series of optical design programs for Hewlett-Packard desktop computers. The latest programs in the series, OSLO-25G and OSLO-45G, have most of the capabilities of general-purpose optical design programs, including optimization based on exact ray-trace data. The computational techniques used in the programs are similar to ones used in other programs, but the creative environment experienced by a designer working directly with these small dedicated systems is typically much different from that obtained with shared-computer systems. Some of the differences are due to the psychological factors associated with using a system having zero running cost, while others are due to the design of the program, which emphasizes graphical output and ease of use, as opposed to computational speed.

  14. Computational design of safer nanomaterials

    NARCIS (Netherlands)

    Burello, E.

    2015-01-01

    Nanomaterials are expected to find applications in numerous consumer products, posing the challenge to guarantee their safety and environmental sustainability before they can be transferred from research labs to end-consumer products. One emerging solution, called safe design, relies on the

  15. Computational Design for Sport Building

    NARCIS (Netherlands)

    Turrin, M.; Yang, D.; D'Aquilio, A.; Šileryte, R.; Sun, Y

    2016-01-01

    The design of sport buildings has great impact on top-sport as well as on recreational sport-activities. It implies challenging tasks in meeting the performance-requirements. This includes the control of factors like daylight/lighting, air flow, thermal conditions, just to name a few. Such factors

  16. Framework for computer-aided systems design

    International Nuclear Information System (INIS)

    Esselman, W.H.

    1992-01-01

    Advanced computer technology, analytical methods, graphics capabilities, and expert systems contribute to significant changes in the design process. Continued progress is expected. Achieving the ultimate benefits of these computer-based design tools depends on successful research and development on a number of key issues. A fundamental understanding of the design process is a prerequisite to developing these computer-based tools. In this paper a hierarchical systems design approach is described, and methods by which computers can assist the designer are examined. A framework is presented for developing computer-based design tools for power plant design. These tools include expert experience bases, tutorials, aids in decision making, and tools to develop the requirements, constraints, and interactions among subsystems and components. Early consideration of the functional tasks is encouraged. Methods of acquiring an expert's experience base is a fundamental research problem. Computer-based guidance should be provided in a manner that supports the creativity, heuristic approaches, decision making, and meticulousness of a good designer

  17. Computer vision based room interior design

    Science.gov (United States)

    Ahmad, Nasir; Hussain, Saddam; Ahmad, Kashif; Conci, Nicola

    2015-12-01

    This paper introduces a new application of computer vision. To the best of the author's knowledge, it is the first attempt to incorporate computer vision techniques into room interior designing. The computer vision based interior designing is achieved in two steps: object identification and color assignment. The image segmentation approach is used for the identification of the objects in the room and different color schemes are used for color assignment to these objects. The proposed approach is applied to simple as well as complex images from online sources. The proposed approach not only accelerated the process of interior designing but also made it very efficient by giving multiple alternatives.

  18. Kinase-Centric Computational Drug Development

    NARCIS (Netherlands)

    Kooistra, Albert J.; Volkamer, Andrea

    2017-01-01

    Kinases are among the most studied drug targets in industry and academia, due to their involvement in a majority of cellular processes and, upon dysregulation, in a variety of diseases including cancer, inflammation, and autoimmune disorders. The high interest in this druggable protein family

  19. Integration of distributed computing into the drug discovery process.

    Science.gov (United States)

    von Korff, Modest; Rufener, Christian; Stritt, Manuel; Freyss, Joel; Bär, Roman; Sander, Thomas

    2011-02-01

    Grid computing offers an opportunity to gain massive computing power at low costs. We give a short introduction into the drug discovery process and exemplify the use of grid computing for image processing, docking and 3D pharmacophore descriptor calculations. The principle of a grid and its architecture are briefly explained. More emphasis is laid on the issues related to a company-wide grid installation and embedding the grid into the research process. The future of grid computing in drug discovery is discussed in the expert opinion section. Most needed, besides reliable algorithms to predict compound properties, is embedding the grid seamlessly into the discovery process. User friendly access to powerful algorithms without any restrictions, that is, by a limited number of licenses, has to be the goal of grid computing in drug discovery.

  20. Generative Recurrent Networks for De Novo Drug Design.

    Science.gov (United States)

    Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

    2018-01-01

    Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  1. A structural keystone for drug design

    Directory of Open Access Journals (Sweden)

    Rother Kristian

    2006-06-01

    Full Text Available 3D-structures of proteins and potential ligands are the cornerstones of rational drug design. The first brick to build upon is selecting a protein target and finding out whether biologically active compounds are known. Both tasks require more information than the structures themselves provide. For this purpose we have built a web resource bridging protein and ligand databases. It consists of three parts: i A data warehouse on annotation of protein structures that integrates many well-known databases such as Swiss-Prot, SCOP, ENZYME and others. ii A conformational library of structures of approved drugs. iii A conformational library of ligands from the PDB, linking the realms of proteins and small molecules.

  2. A survey of current trends in computational drug repositioning.

    Science.gov (United States)

    Li, Jiao; Zheng, Si; Chen, Bin; Butte, Atul J; Swamidass, S Joshua; Lu, Zhiyong

    2016-01-01

    Computational drug repositioning or repurposing is a promising and efficient tool for discovering new uses from existing drugs and holds the great potential for precision medicine in the age of big data. The explosive growth of large-scale genomic and phenotypic data, as well as data of small molecular compounds with granted regulatory approval, is enabling new developments for computational repositioning. To achieve the shortest path toward new drug indications, advanced data processing and analysis strategies are critical for making sense of these heterogeneous molecular measurements. In this review, we show recent advancements in the critical areas of computational drug repositioning from multiple aspects. First, we summarize available data sources and the corresponding computational repositioning strategies. Second, we characterize the commonly used computational techniques. Third, we discuss validation strategies for repositioning studies, including both computational and experimental methods. Finally, we highlight potential opportunities and use-cases, including a few target areas such as cancers. We conclude with a brief discussion of the remaining challenges in computational drug repositioning. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.

  3. Structured Design Language for Computer Programs

    Science.gov (United States)

    Pace, Walter H., Jr.

    1986-01-01

    Box language used at all stages of program development. Developed to provide improved productivity in designing, coding, and maintaining computer programs. BOX system written in FORTRAN 77 for batch execution.

  4. Computational network design from functional specifications

    KAUST Repository

    Peng, Chi Han; Yang, Yong Liang; Bao, Fan; Fink, Daniel; Yan, Dongming; Wonka, Peter; Mitra, Niloy J.

    2016-01-01

    of people in a workspace. Designing such networks from scratch is challenging as even local network changes can have large global effects. We investigate how to computationally create networks starting from only high-level functional specifications

  5. Cloud Computing Techniques for Space Mission Design

    Science.gov (United States)

    Arrieta, Juan; Senent, Juan

    2014-01-01

    The overarching objective of space mission design is to tackle complex problems producing better results, and faster. In developing the methods and tools to fulfill this objective, the user interacts with the different layers of a computing system.

  6. Computer codes for RF cavity design

    International Nuclear Information System (INIS)

    Ko, K.

    1992-08-01

    In RF cavity design, numerical modeling is assuming an increasingly important role with the help of sophisticated computer codes and powerful yet affordable computers. A description of the cavity codes in use in the accelerator community has been given previously. The present paper will address the latest developments and discuss their applications to cavity toning and matching problems

  7. Computer aided design of solonoid magnets

    Energy Technology Data Exchange (ETDEWEB)

    DeOlivares, J.M.

    1978-06-01

    Computer programs utilizing Legendre functions and elliptic integral functions have been written to aid in the design of solenoid magnets. The field inside an axisymmetric magnet can be expanded in a converging power series of Legendre functions. The Legendre function approach is very useful for designing solenoid magnets with a high degree of field uniformity. This approach has been programed on the LBL CDC 7600 computer so that one can design an axisymmetric magnet which meets any desired field structure. Two examples of computer designed solenoids are presented. A computer program utilizing elliptic integral functions was also written for the LBL CDC 7600 computer. This method was used in a computer program to verify the results obtained from the Legendre approach and for field calculations within the conductor. The elliptic integral field calculations within the conductor showed that thin solenoids produce field peaking at the ends of the magnet. Computer data is generated for various magnet geometries and compared with theoretical predictions. Computer results and theoretical prediction both show that field peaking is reduced for longer coils, increased for thinner coils and field peaking is a logarithmic function of length, thickness and radius.

  8. Computing tools for accelerator design calculations

    International Nuclear Information System (INIS)

    Fischler, M.; Nash, T.

    1984-01-01

    This note is intended as a brief, summary guide for accelerator designers to the new generation of commercial and special processors that allow great increases in computing cost effectiveness. New thinking is required to take best advantage of these computing opportunities, in particular, when moving from analytical approaches to tracking simulations. In this paper, we outline the relevant considerations

  9. Computer codes for RF cavity design

    International Nuclear Information System (INIS)

    Ko, K.

    1992-01-01

    In RF cavity design, numerical modeling is assuming an increasingly important role with the help of sophisticated computer codes and powerful yet affordable computers. A description of the cavity codes in use in the accelerator community has been given previously. The present paper will address the latest developments and discuss their applications to cavity tuning and matching problems. (Author) 8 refs., 10 figs

  10. Computer System Design System-on-Chip

    CERN Document Server

    Flynn, Michael J

    2011-01-01

    The next generation of computer system designers will be less concerned about details of processors and memories, and more concerned about the elements of a system tailored to particular applications. These designers will have a fundamental knowledge of processors and other elements in the system, but the success of their design will depend on the skills in making system-level tradeoffs that optimize the cost, performance and other attributes to meet application requirements. This book provides a new treatment of computer system design, particularly for System-on-Chip (SOC), which addresses th

  11. Computer aided design for the nuclear industry

    International Nuclear Information System (INIS)

    Basson, Keith

    1986-01-01

    The paper concerns the new computer aided design (CAD) centre for the United Kingdom nuclear industry, and its applications. A description of the CAD system is given, including the current projects at the CAD centre. Typical applications of the 3D CAD plant based models, stress analysis studies, and the extraction of data from CAD drawings to produce associated documentation, are all described. Future developments using computer aided design systems are also considered. (U.K.)

  12. Fragment-based drug discovery and molecular docking in drug design.

    Science.gov (United States)

    Wang, Tao; Wu, Mian-Bin; Chen, Zheng-Jie; Chen, Hua; Lin, Jian-Ping; Yang, Li-Rong

    2015-01-01

    Fragment-based drug discovery (FBDD) has caused a revolution in the process of drug discovery and design, with many FBDD leads being developed into clinical trials or approved in the past few years. Compared with traditional high-throughput screening, it displays obvious advantages such as efficiently covering chemical space, achieving higher hit rates, and so forth. In this review, we focus on the most recent developments of FBDD for improving drug discovery, illustrating the process and the importance of FBDD. In particular, the computational strategies applied in the process of FBDD and molecular-docking programs are highlighted elaborately. In most cases, docking is used for predicting the ligand-receptor interaction modes and hit identification by structurebased virtual screening. The successful cases of typical significance and the hits identified most recently are discussed.

  13. Performative Computation-aided Design Optimization

    Directory of Open Access Journals (Sweden)

    Ming Tang

    2012-12-01

    Full Text Available This article discusses a collaborative research and teaching project between the University of Cincinnati, Perkins+Will’s Tech Lab, and the University of North Carolina Greensboro. The primary investigation focuses on the simulation, optimization, and generation of architectural designs using performance-based computational design approaches. The projects examine various design methods, including relationships between building form, performance and the use of proprietary software tools for parametric design.

  14. Computer code development plant for SMART design

    International Nuclear Information System (INIS)

    Bae, Kyoo Hwan; Choi, S.; Cho, B.H.; Kim, K.K.; Lee, J.C.; Kim, J.P.; Kim, J.H.; Chung, M.; Kang, D.J.; Chang, M.H.

    1999-03-01

    In accordance with the localization plan for the nuclear reactor design driven since the middle of 1980s, various computer codes have been transferred into the korea nuclear industry through the technical transfer program from the worldwide major pressurized water reactor supplier or through the international code development program. These computer codes have been successfully utilized in reactor and reload core design works. As the results, design- related technologies have been satisfactorily accumulated. However, the activities for the native code development activities to substitute the some important computer codes of which usages are limited by the original technique owners have been carried out rather poorly. Thus, it is most preferentially required to secure the native techniques on the computer code package and analysis methodology in order to establish the capability required for the independent design of our own model of reactor. Moreover, differently from the large capacity loop-type commercial reactors, SMART (SYSTEM-integrated Modular Advanced ReacTor) design adopts a single reactor pressure vessel containing the major primary components and has peculiar design characteristics such as self-controlled gas pressurizer, helical steam generator, passive residual heat removal system, etc. Considering those peculiar design characteristics for SMART, part of design can be performed with the computer codes used for the loop-type commercial reactor design. However, most of those computer codes are not directly applicable to the design of an integral reactor such as SMART. Thus, they should be modified to deal with the peculiar design characteristics of SMART. In addition to the modification efforts, various codes should be developed in several design area. Furthermore, modified or newly developed codes should be verified their reliability through the benchmarking or the test for the object design. Thus, it is necessary to proceed the design according to the

  15. Computer code development plant for SMART design

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyoo Hwan; Choi, S.; Cho, B.H.; Kim, K.K.; Lee, J.C.; Kim, J.P.; Kim, J.H.; Chung, M.; Kang, D.J.; Chang, M.H

    1999-03-01

    In accordance with the localization plan for the nuclear reactor design driven since the middle of 1980s, various computer codes have been transferred into the korea nuclear industry through the technical transfer program from the worldwide major pressurized water reactor supplier or through the international code development program. These computer codes have been successfully utilized in reactor and reload core design works. As the results, design- related technologies have been satisfactorily accumulated. However, the activities for the native code development activities to substitute the some important computer codes of which usages are limited by the original technique owners have been carried out rather poorly. Thus, it is most preferentially required to secure the native techniques on the computer code package and analysis methodology in order to establish the capability required for the independent design of our own model of reactor. Moreover, differently from the large capacity loop-type commercial reactors, SMART (SYSTEM-integrated Modular Advanced ReacTor) design adopts a single reactor pressure vessel containing the major primary components and has peculiar design characteristics such as self-controlled gas pressurizer, helical steam generator, passive residual heat removal system, etc. Considering those peculiar design characteristics for SMART, part of design can be performed with the computer codes used for the loop-type commercial reactor design. However, most of those computer codes are not directly applicable to the design of an integral reactor such as SMART. Thus, they should be modified to deal with the peculiar design characteristics of SMART. In addition to the modification efforts, various codes should be developed in several design area. Furthermore, modified or newly developed codes should be verified their reliability through the benchmarking or the test for the object design. Thus, it is necessary to proceed the design according to the

  16. Computer Aided Solvent Selection and Design Framework

    DEFF Research Database (Denmark)

    Mitrofanov, Igor; Conte, Elisa; Abildskov, Jens

    and computer-aided tools and methods for property prediction and computer-aided molecular design (CAMD) principles. This framework is applicable for solvent selection and design in product design as well as process design. The first module of the framework is dedicated to the solvent selection and design...... in terms of: physical and chemical properties (solvent-pure properties); Environment, Health and Safety (EHS) characteristic (solvent-EHS properties); operational properties (solvent–solute properties). 3. Performing the search. The search step consists of two stages. The first is a generation and property...... identification of solvent candidates using special software ProCAMD and ProPred, which are the implementations of computer-aided molecular techniques. The second consists of assigning the RS-indices following the reaction–solvent and then consulting the known solvent database and identifying the set of solvents...

  17. Logical design for computers and control

    CERN Document Server

    Dodd, Kenneth N

    1972-01-01

    Logical Design for Computers and Control Logical Design for Computers and Control gives an introduction to the concepts and principles, applications, and advancements in the field of control logic. The text covers topics such as logic elements; high and low logic; kinds of flip-flops; binary counting and arithmetic; and Boolean algebra, Boolean laws, and De Morgan's theorem. Also covered are topics such as electrostatics and atomic theory; the integrated circuit and simple control systems; the conversion of analog to digital systems; and computer applications and control. The book is recommend

  18. Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles.

    Science.gov (United States)

    Gayathri, N K; Aparna, V; Maya, S; Biswas, Raja; Jayakumar, R; Mohan, C Gopi

    2017-12-01

    We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were -7.3kcal/mol, -5.1kcal/mol and -8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Kurver for Computer Assisteret Geometrisk Design

    DEFF Research Database (Denmark)

    Gravesen, Jens

    1999-01-01

    Dette hæfte indeholder en introduktion til computer assisteret geometrisk design (CAGD). der argumenteres for, at kurver udtrykt ved hjælp af polynomier er velegnede til design formål og at det specielt er attraktivt at bruge dem i form af Bézier-kurver.Med udgangspunkt i de Casteljau's algoritme...

  20. Computation for the analysis of designed experiments

    CERN Document Server

    Heiberger, Richard

    2015-01-01

    Addresses the statistical, mathematical, and computational aspects of the construction of packages and analysis of variance (ANOVA) programs. Includes a disk at the back of the book that contains all program codes in four languages, APL, BASIC, C, and FORTRAN. Presents illustrations of the dual space geometry for all designs, including confounded designs.

  1. Phytosterols and anabolic agents versus designer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Brabander, H.F. de [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)]. E-mail: Hubert.DeBrabander@UGent.be; Verheyden, K. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Mortier, V. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Le Bizec, B. [LABERCA, Ecole Nationale Veterinaire de Nantes, BP 50707, F-44087 Nantes Cedex 03 (France); Verbeke, W. [Ghent University, Department of Agricultural Economics, Coupure links 653, B-9000 Ghent (Belgium); Courtheyn, D. [Federal Feed and Food Laboratory, Braemkasteelstraat 59, B-9050 Ghentbruges (Belgium); Noppe, H. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)

    2007-03-14

    Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the {sup 13}C/{sup 12}C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse.

  2. Phytosterols and anabolic agents versus designer drugs

    International Nuclear Information System (INIS)

    Brabander, H.F. de; Verheyden, K.; Mortier, V.; Le Bizec, B.; Verbeke, W.; Courtheyn, D.; Noppe, H.

    2007-01-01

    Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the 13 C/ 12 C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse

  3. e-Drug3D: 3D structure collections dedicated to drug repurposing and fragment-based drug design.

    Science.gov (United States)

    Pihan, Emilie; Colliandre, Lionel; Guichou, Jean-François; Douguet, Dominique

    2012-06-01

    In the drug discovery field, new uses for old drugs, selective optimization of side activities and fragment-based drug design (FBDD) have proved to be successful alternatives to high-throughput screening. e-Drug3D is a database of 3D chemical structures of drugs that provides several collections of ready-to-screen SD files of drugs and commercial drug fragments. They are natural inputs in studies dedicated to drug repurposing and FBDD. e-Drug3D collections are freely available at http://chemoinfo.ipmc.cnrs.fr/e-drug3d.html either for download or for direct in silico web-based screenings.

  4. Electromagnetic Compatibility Design of the Computer Circuits

    Science.gov (United States)

    Zitai, Hong

    2018-02-01

    Computers and the Internet have gradually penetrated into every aspect of people’s daily work. But with the improvement of electronic equipment as well as electrical system, the electromagnetic environment becomes much more complex. Electromagnetic interference has become an important factor to hinder the normal operation of electronic equipment. In order to analyse the computer circuit compatible with the electromagnetic compatibility, this paper starts from the computer electromagnetic and the conception of electromagnetic compatibility. And then, through the analysis of the main circuit and system of computer electromagnetic compatibility problems, we can design the computer circuits in term of electromagnetic compatibility. Finally, the basic contents and methods of EMC test are expounded in order to ensure the electromagnetic compatibility of equipment.

  5. Fundamentals of computer architecture and design

    CERN Document Server

    Bindal, Ahmet

    2017-01-01

    This textbook provides semester-length coverage of computer architecture and design, providing a strong foundation for students to understand modern computer system architecture and to apply these insights and principles to future computer designs.  It is based on the author’s decades of industrial experience with computer architecture and design, as well as with teaching students focused on pursuing careers in computer engineering.  Unlike a number of existing textbooks for this course, this one focuses not only on CPU architecture, but also covers in great detail in system buses, peripherals and memories.This book teaches every element in a computing system in two steps.  First, it introduces the functionality of each topic (and subtopics) and then goes into “from-scratch design” of a particular digital block from its architectural specifications using timing diagrams.  The author describes how the data-path of a certain digital block is generated using timin g diagrams, a method which most textbo...

  6. Computer Language For Optimization Of Design

    Science.gov (United States)

    Scotti, Stephen J.; Lucas, Stephen H.

    1991-01-01

    SOL is computer language geared to solution of design problems. Includes mathematical modeling and logical capabilities of computer language like FORTRAN; also includes additional power of nonlinear mathematical programming methods at language level. SOL compiler takes SOL-language statements and generates equivalent FORTRAN code and system calls. Provides syntactic and semantic checking for recovery from errors and provides detailed reports containing cross-references to show where each variable used. Implemented on VAX/VMS computer systems. Requires VAX FORTRAN compiler to produce executable program.

  7. Cloud computing approaches to accelerate drug discovery value chain.

    Science.gov (United States)

    Garg, Vibhav; Arora, Suchir; Gupta, Chitra

    2011-12-01

    Continued advancements in the area of technology have helped high throughput screening (HTS) evolve from a linear to parallel approach by performing system level screening. Advanced experimental methods used for HTS at various steps of drug discovery (i.e. target identification, target validation, lead identification and lead validation) can generate data of the order of terabytes. As a consequence, there is pressing need to store, manage, mine and analyze this data to identify informational tags. This need is again posing challenges to computer scientists to offer the matching hardware and software infrastructure, while managing the varying degree of desired computational power. Therefore, the potential of "On-Demand Hardware" and "Software as a Service (SAAS)" delivery mechanisms cannot be denied. This on-demand computing, largely referred to as Cloud Computing, is now transforming the drug discovery research. Also, integration of Cloud computing with parallel computing is certainly expanding its footprint in the life sciences community. The speed, efficiency and cost effectiveness have made cloud computing a 'good to have tool' for researchers, providing them significant flexibility, allowing them to focus on the 'what' of science and not the 'how'. Once reached to its maturity, Discovery-Cloud would fit best to manage drug discovery and clinical development data, generated using advanced HTS techniques, hence supporting the vision of personalized medicine.

  8. Integrated computer-aided design using minicomputers

    Science.gov (United States)

    Storaasli, O. O.

    1980-01-01

    Computer-Aided Design/Computer-Aided Manufacturing (CAD/CAM), a highly interactive software, has been implemented on minicomputers at the NASA Langley Research Center. CAD/CAM software integrates many formerly fragmented programs and procedures into one cohesive system; it also includes finite element modeling and analysis, and has been interfaced via a computer network to a relational data base management system and offline plotting devices on mainframe computers. The CAD/CAM software system requires interactive graphics terminals operating at a minimum of 4800 bits/sec transfer rate to a computer. The system is portable and introduces 'interactive graphics', which permits the creation and modification of models interactively. The CAD/CAM system has already produced designs for a large area space platform, a national transonic facility fan blade, and a laminar flow control wind tunnel model. Besides the design/drafting element analysis capability, CAD/CAM provides options to produce an automatic program tooling code to drive a numerically controlled (N/C) machine. Reductions in time for design, engineering, drawing, finite element modeling, and N/C machining will benefit productivity through reduced costs, fewer errors, and a wider range of configuration.

  9. Computational Design of Molecularly Imprinted Polymers

    Science.gov (United States)

    Subrahmanyam, Sreenath; Piletsky, Sergey A.

    Artificial receptors have been in use for several decades as sensor elements, in affinity separation, and as models for investigation of molecular recognition. Although there have been numerous publications on the use of molecular modeling in characterization of their affinity and selectivity, very few attempts have been made on the application of molecular modeling in computational design of synthetic receptors. This chapter discusses recent successes in the use of computational design for the development of one particular branch of synthetic receptors - molecularly imprinted polymers.

  10. Mechanical Design Technology--Modified. (Computer Assisted Drafting, Computer Aided Design). Curriculum Grant 84/85.

    Science.gov (United States)

    Schoolcraft Coll., Livonia, MI.

    This document is a curriculum guide for a program in mechanical design technology (computer-assisted drafting and design developed at Schoolcraft College, Livonia, Michigan). The program helps students to acquire the skills of drafters and to interact with electronic equipment, with the option of becoming efficient in the computer-aided…

  11. CAAD as Computer-Activated Architectural Design

    DEFF Research Database (Denmark)

    Galle, Per

    1998-01-01

    In a brief sketch, drawing on a general philosophical conception of human interaction with the world, the architectural design process is analysed in terms of two kinds of human action: interpretation and production. Both of these are seen as establishing a link between mental and material entities....... On this background two alternative roles of computers in computer-aided architectural design (CAAD) are distinguished: a passive and a more active role, where in the latter case, the computer’s capacity for symbol manipulation is utilized to influence design thinking actively. The analysis offered in this paper may...... serve at least two purposes: to provide a conceptual machinery for research and reflection on CAAD, and to clarify the notion of ‘artificial intelligence’ in the light of architectural design....

  12. Computational fluid dynamics in ventilation design

    CERN Document Server

    Allard, Francis; Awbi, Hazim B; Davidson, Lars; Schälin, Alois

    2007-01-01

    CFD-calculations have been rapidly developed to a powerful tool for the analysis of air pollution distribution in various spaces. However, the user of CFD-calculation should be aware of the basic principles of calculations and specifically the boundary conditions. Computational Fluid Dynamics (CFD) – in Ventilation Design models is written by a working group of highly qualified international experts representing research, consulting and design.

  13. Mathematical modeling and computational prediction of cancer drug resistance.

    Science.gov (United States)

    Sun, Xiaoqiang; Hu, Bin

    2017-06-23

    Diverse forms of resistance to anticancer drugs can lead to the failure of chemotherapy. Drug resistance is one of the most intractable issues for successfully treating cancer in current clinical practice. Effective clinical approaches that could counter drug resistance by restoring the sensitivity of tumors to the targeted agents are urgently needed. As numerous experimental results on resistance mechanisms have been obtained and a mass of high-throughput data has been accumulated, mathematical modeling and computational predictions using systematic and quantitative approaches have become increasingly important, as they can potentially provide deeper insights into resistance mechanisms, generate novel hypotheses or suggest promising treatment strategies for future testing. In this review, we first briefly summarize the current progress of experimentally revealed resistance mechanisms of targeted therapy, including genetic mechanisms, epigenetic mechanisms, posttranslational mechanisms, cellular mechanisms, microenvironmental mechanisms and pharmacokinetic mechanisms. Subsequently, we list several currently available databases and Web-based tools related to drug sensitivity and resistance. Then, we focus primarily on introducing some state-of-the-art computational methods used in drug resistance studies, including mechanism-based mathematical modeling approaches (e.g. molecular dynamics simulation, kinetic model of molecular networks, ordinary differential equation model of cellular dynamics, stochastic model, partial differential equation model, agent-based model, pharmacokinetic-pharmacodynamic model, etc.) and data-driven prediction methods (e.g. omics data-based conventional screening approach for node biomarkers, static network approach for edge biomarkers and module biomarkers, dynamic network approach for dynamic network biomarkers and dynamic module network biomarkers, etc.). Finally, we discuss several further questions and future directions for the use of

  14. Computer aided architectural design : futures 2001

    NARCIS (Netherlands)

    Vries, de B.; Leeuwen, van J.P.; Achten, H.H.

    2001-01-01

    CAAD Futures is a bi-annual conference that aims to promote the advancement of computer-aided architectural design in the service of those concerned with the quality of the built environment. The conferences are organized under the auspices of the CAAD Futures Foundation, which has its secretariat

  15. Slab cooling system design using computer simulation

    NARCIS (Netherlands)

    Lain, M.; Zmrhal, V.; Drkal, F.; Hensen, J.L.M.

    2007-01-01

    For a new technical library building in Prague computer simulations were carried out to help design of slab cooling system and optimize capacity of chillers. In the paper is presented concept of new technical library HVAC system, the model of the building, results of the energy simulations for

  16. Computationally designed libraries for rapid enzyme stabilization

    NARCIS (Netherlands)

    Wijma, Hein J.; Floor, Robert J.; Jekel, Peter A.; Baker, David; Marrink, Siewert J.; Janssen, Dick B.

    The ability to engineer enzymes and other proteins to any desired stability would have wide-ranging applications. Here, we demonstrate that computational design of a library with chemically diverse stabilizing mutations allows the engineering of drastically stabilized and fully functional variants

  17. Ethics in computer software design and development

    Science.gov (United States)

    Alan J. Thomson; Daniel L. Schmoldt

    2001-01-01

    Over the past 20 years, computer software has become integral and commonplace for operational and management tasks throughout agricultural and natural resource disciplines. During this software infusion, however, little thought has been afforded human impacts, both good and bad. This paper examines current ethical issues of software system design and development in...

  18. Social things : design research on social computing

    NARCIS (Netherlands)

    Hu, J.; Luen, P.; Rau, P.

    2016-01-01

    In the era of social networking and computing, things and people are more and more interconnected, giving rise to not only new opportunities but also new challenges in designing new products that are networked, and services that are adaptive to their human users and context aware in their physical

  19. Computer-Aided Design in Further Education.

    Science.gov (United States)

    Ingham, Peter, Ed.

    This publication updates the 1982 occasional paper that was intended to foster staff awareness and assist colleges in Great Britain considering the use of computer-aided design (CAD) material in engineering courses. The paper begins by defining CAD and its place in the Integrated Business System with a brief discussion of the effect of CAD on the…

  20. Design and computation of modern engineering materials

    CERN Document Server

    Altenbach, Holm

    2014-01-01

     The idea of this monograph is to present the latest results related to design and computation of engineering materials and structures. The contributions cover the classical fields of mechanical, civil and materials engineering up to biomechanics and advanced materials processing and optimization. The materials and structures covered can be categorized into modern steels and titanium alloys, composite materials, biological and natural materials, material hybrids and modern joining technologies. Analytical modelling, numerical simulation, the application of state-of-the-art design tools and sophisticated experimental techniques are applied to characterize the performance of materials and to design and optimize structures in different fields of engineering applications.

  1. Computational Chemical Synthesis Analysis and Pathway Design

    Directory of Open Access Journals (Sweden)

    Fan Feng

    2018-06-01

    Full Text Available With the idea of retrosynthetic analysis, which was raised in the 1960s, chemical synthesis analysis and pathway design have been transformed from a complex problem to a regular process of structural simplification. This review aims to summarize the developments of computer-assisted synthetic analysis and design in recent years, and how machine-learning algorithms contributed to them. LHASA system started the pioneering work of designing semi-empirical reaction modes in computers, with its following rule-based and network-searching work not only expanding the databases, but also building new approaches to indicating reaction rules. Programs like ARChem Route Designer replaced hand-coded reaction modes with automatically-extracted rules, and programs like Chematica changed traditional designing into network searching. Afterward, with the help of machine learning, two-step models which combine reaction rules and statistical methods became the main stream. Recently, fully data-driven learning methods using deep neural networks which even do not require any prior knowledge, were applied into this field. Up to now, however, these methods still cannot replace experienced human organic chemists due to their relatively low accuracies. Future new algorithms with the aid of powerful computational hardware will make this topic promising and with good prospects.

  2. Computer-assisted spectral design and synthesis

    Science.gov (United States)

    Vadakkumpadan, Fijoy; Wang, Qiqi; Sun, Yinlong

    2005-01-01

    In this paper, we propose a computer-assisted approach for spectral design and synthesis. This approach starts with some initial spectrum, modifies it interactively, evaluates the change, and decides the optimal spectrum. Given a requested change as function of wavelength, we model the change function using a Gaussian function. When there is the metameric constraint, from the Gaussian function of request change, we propose a method to generate the change function such that the result spectrum has the same color as the initial spectrum. We have tested the proposed method with different initial spectra and change functions, and implemented an interactive graphics environment for spectral design and synthesis. The proposed approach and graphics implementation for spectral design and synthesis can be helpful for a number of applications such as lighting of building interiors, textile coloration, and pigment development of automobile paints, and spectral computer graphics.

  3. Protein Crystallography: A 'Must' Technology for Drug Design

    International Nuclear Information System (INIS)

    Matsuzaki, Takao

    2004-01-01

    The history of drug-related protein crystallography and drug design is reviewed to show that 'Lead Generation' is high-lighted in the pharmaceutical industry nowadays. A new drug design method has been developed. The method gave very high success rate; 10-60 % gave < 100 μM, 90 % gave < 10 mM. The crystal structures of drug-protein complexes have become even more important to give solid experimental bases for e.g. 1,000 designed structures and to find the new mechanisms of drug action

  4. Geometric modeling for computer aided design

    Science.gov (United States)

    Schwing, James L.; Olariu, Stephen

    1995-01-01

    The primary goal of this grant has been the design and implementation of software to be used in the conceptual design of aerospace vehicles particularly focused on the elements of geometric design, graphical user interfaces, and the interaction of the multitude of software typically used in this engineering environment. This has resulted in the development of several analysis packages and design studies. These include two major software systems currently used in the conceptual level design of aerospace vehicles. These tools are SMART, the Solid Modeling Aerospace Research Tool, and EASIE, the Environment for Software Integration and Execution. Additional software tools were designed and implemented to address the needs of the engineer working in the conceptual design environment. SMART provides conceptual designers with a rapid prototyping capability and several engineering analysis capabilities. In addition, SMART has a carefully engineered user interface that makes it easy to learn and use. Finally, a number of specialty characteristics have been built into SMART which allow it to be used efficiently as a front end geometry processor for other analysis packages. EASIE provides a set of interactive utilities that simplify the task of building and executing computer aided design systems consisting of diverse, stand-alone, analysis codes. Resulting in a streamlining of the exchange of data between programs reducing errors and improving the efficiency. EASIE provides both a methodology and a collection of software tools to ease the task of coordinating engineering design and analysis codes.

  5. Computer codes for designing proton linear accelerators

    International Nuclear Information System (INIS)

    Kato, Takao

    1992-01-01

    Computer codes for designing proton linear accelerators are discussed from the viewpoint of not only designing but also construction and operation of the linac. The codes are divided into three categories according to their purposes: 1) design code, 2) generation and simulation code, and 3) electric and magnetic fields calculation code. The role of each category is discussed on the basis of experience at KEK (the design of the 40-MeV proton linac and its construction and operation, and the design of the 1-GeV proton linac). We introduce our recent work relevant to three-dimensional calculation and supercomputer calculation: 1) tuning of MAFIA (three-dimensional electric and magnetic fields calculation code) for supercomputer, 2) examples of three-dimensional calculation of accelerating structures by MAFIA, 3) development of a beam transport code including space charge effects. (author)

  6. Designing Scientific Software for Heterogeneous Computing

    DEFF Research Database (Denmark)

    Glimberg, Stefan Lemvig

    , algorithms and data structures must be designed to utilize the underlying parallel architecture. The architectural changes in hardware design within the last decade, from single to multi and many-core architectures, require software developers to identify and properly implement methods that both exploit...... makes parallel software design applicable, but also a challenge for scientific software developers at all levels. We have developed a generic C++ library for fast prototyping of large-scale PDEs solvers based on flexible-order finite difference approximations on structured regular grids. The library...... is designed with a high abstraction interface to improve developer productivity. The library is based on modern template-based design concepts as described in Glimberg, Engsig-Karup, Nielsen & Dammann (2013). The library utilizes heterogeneous CPU/GPU environments in order to maximize computational throughput...

  7. Grid Based Technologies for in silico Screening and Drug Design.

    Science.gov (United States)

    Potemkin, Vladimir; Grishina, Maria

    2018-03-08

    Various techniques for rational drug design are presented in the paper. The methods are based on a substitution of antipharmacophore atoms of the molecules of training dataset by new atoms and/or group of atoms increasing the atomic bioactivity increments obtained at a SAR study. Furthermore, a design methodology based on the genetic algorithm DesPot for discrete optimization and generation of new drug candidate structures is described. Additionally, wide spectra of SAR approaches (3D/4D QSAR interior and exterior-based methods - BiS, CiS, ConGO, CoMIn, high-quality docking method - ReDock) using MERA force field and/or AlteQ quantum chemical method for correct prognosis of bioactivity and bioactive probability is described. The design methods are implemented now at www.chemosophia.com web-site for online computational services. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Towards the computational design of solid catalysts

    DEFF Research Database (Denmark)

    Nørskov, Jens Kehlet; Bligaard, Thomas; Rossmeisl, Jan

    2009-01-01

    Over the past decade the theoretical description of surface reactions has undergone a radical development. Advances in density functional theory mean it is now possible to describe catalytic reactions at surfaces with the detail and accuracy required for computational results to compare favourably...... with experiments. Theoretical methods can be used to describe surface chemical reactions in detail and to understand variations in catalytic activity from one catalyst to another. Here, we review the first steps towards using computational methods to design new catalysts. Examples include screening for catalysts...

  9. Autonomic computing enabled cooperative networked design

    CERN Document Server

    Wodczak, Michal

    2014-01-01

    This book introduces the concept of autonomic computing driven cooperative networked system design from an architectural perspective. As such it leverages and capitalises on the relevant advancements in both the realms of autonomic computing and networking by welding them closely together. In particular, a multi-faceted Autonomic Cooperative System Architectural Model is defined which incorporates the notion of Autonomic Cooperative Behaviour being orchestrated by the Autonomic Cooperative Networking Protocol of a cross-layer nature. The overall proposed solution not only advocates for the inc

  10. Bioinformatics in cancer therapy and drug design

    International Nuclear Information System (INIS)

    Horbach, D.Y.; Usanov, S.A.

    2005-01-01

    One of the mechanisms of external signal transduction (ionizing radiation, toxicants, stress) to the target cell is the existence of membrane and intracellular proteins with intrinsic tyrosine kinase activity. No wonder that etiology of malignant growth links to abnormalities in signal transduction through tyrosine kinases. The epidermal growth factor receptor (EGFR) tyrosine kinases play fundamental roles in development, proliferation and differentiation of tissues of epithelial, mesenchymal and neuronal origin. There are four types of EGFR: EGF receptor (ErbB1/HER1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. Abnormal expression of EGFR, appearance of receptor mutants with changed ability to protein-protein interactions or increased tyrosine kinase activity have been implicated in the malignancy of different types of human tumors. Bioinformatics is currently using in investigation on design and selection of drugs that can make alterations in structure or competitively bind with receptors and so display antagonistic characteristics. (authors)

  11. Bioinformatics in cancer therapy and drug design

    Energy Technology Data Exchange (ETDEWEB)

    Horbach, D Y [International A. Sakharov environmental univ., Minsk (Belarus); Usanov, S A [Inst. of bioorganic chemistry, National academy of sciences of Belarus, Minsk (Belarus)

    2005-05-15

    One of the mechanisms of external signal transduction (ionizing radiation, toxicants, stress) to the target cell is the existence of membrane and intracellular proteins with intrinsic tyrosine kinase activity. No wonder that etiology of malignant growth links to abnormalities in signal transduction through tyrosine kinases. The epidermal growth factor receptor (EGFR) tyrosine kinases play fundamental roles in development, proliferation and differentiation of tissues of epithelial, mesenchymal and neuronal origin. There are four types of EGFR: EGF receptor (ErbB1/HER1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. Abnormal expression of EGFR, appearance of receptor mutants with changed ability to protein-protein interactions or increased tyrosine kinase activity have been implicated in the malignancy of different types of human tumors. Bioinformatics is currently using in investigation on design and selection of drugs that can make alterations in structure or competitively bind with receptors and so display antagonistic characteristics. (authors)

  12. Scaling predictive modeling in drug development with cloud computing.

    Science.gov (United States)

    Moghadam, Behrooz Torabi; Alvarsson, Jonathan; Holm, Marcus; Eklund, Martin; Carlsson, Lars; Spjuth, Ola

    2015-01-26

    Growing data sets with increased time for analysis is hampering predictive modeling in drug discovery. Model building can be carried out on high-performance computer clusters, but these can be expensive to purchase and maintain. We have evaluated ligand-based modeling on cloud computing resources where computations are parallelized and run on the Amazon Elastic Cloud. We trained models on open data sets of varying sizes for the end points logP and Ames mutagenicity and compare with model building parallelized on a traditional high-performance computing cluster. We show that while high-performance computing results in faster model building, the use of cloud computing resources is feasible for large data sets and scales well within cloud instances. An additional advantage of cloud computing is that the costs of predictive models can be easily quantified, and a choice can be made between speed and economy. The easy access to computational resources with no up-front investments makes cloud computing an attractive alternative for scientists, especially for those without access to a supercomputer, and our study shows that it enables cost-efficient modeling of large data sets on demand within reasonable time.

  13. A systematic investigation of computation models for predicting Adverse Drug Reactions (ADRs.

    Directory of Open Access Journals (Sweden)

    Qifan Kuang

    Full Text Available Early and accurate identification of adverse drug reactions (ADRs is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs.In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper.Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms.

  14. A systematic investigation of computation models for predicting Adverse Drug Reactions (ADRs).

    Science.gov (United States)

    Kuang, Qifan; Wang, MinQi; Li, Rong; Dong, YongCheng; Li, Yizhou; Li, Menglong

    2014-01-01

    Early and accurate identification of adverse drug reactions (ADRs) is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs. In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper. Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms.

  15. Reliable computer systems design and evaluatuion

    CERN Document Server

    Siewiorek, Daniel

    2014-01-01

    Enhance your hardware/software reliabilityEnhancement of system reliability has been a major concern of computer users and designers ¦ and this major revision of the 1982 classic meets users' continuing need for practical information on this pressing topic. Included are case studies of reliablesystems from manufacturers such as Tandem, Stratus, IBM, and Digital, as well as coverage of special systems such as the Galileo Orbiter fault protection system and AT&T telephone switching processors.

  16. Soft Computing Methods in Design of Superalloys

    Science.gov (United States)

    Cios, K. J.; Berke, L.; Vary, A.; Sharma, S.

    1996-01-01

    Soft computing techniques of neural networks and genetic algorithms are used in the design of superalloys. The cyclic oxidation attack parameter K(sub a), generated from tests at NASA Lewis Research Center, is modelled as a function of the superalloy chemistry and test temperature using a neural network. This model is then used in conjunction with a genetic algorithm to obtain an optimized superalloy composition resulting in low K(sub a) values.

  17. Drug design: structure- and ligand-based approaches

    National Research Council Canada - National Science Library

    Merz, Kenneth M; Ringe, Dagmar; Reynolds, Charles H

    2010-01-01

    ..., computational ADME-Tox, and drug discovery case studies. A variety of authors from academic and commercial institutions all over the world have contributed to this book, which is illustrated with more than 200 images...

  18. NMR in structure-based drug design.

    Science.gov (United States)

    Carneiro, Marta G; Ab, Eiso; Theisgen, Stephan; Siegal, Gregg

    2017-11-08

    NMR spectroscopy is a powerful technique that can provide valuable structural information for drug discovery endeavors. Here, we discuss the strengths (and limitations) of NMR applications to structure-based drug discovery, highlighting the different levels of resolution and throughput obtainable. Additionally, the emerging field of paramagnetic NMR in drug discovery and recent developments in approaches to speed up and automate protein-observed NMR data collection and analysis are discussed. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  19. Computational and experimental model of transdermal iontophorethic drug delivery system.

    Science.gov (United States)

    Filipovic, Nenad; Saveljic, Igor; Rac, Vladislav; Graells, Beatriz Olalde; Bijelic, Goran

    2017-11-30

    The concept of iontophoresis is often applied to increase the transdermal transport of drugs and other bioactive agents into the skin or other tissues. It is a non-invasive drug delivery method which involves electromigration and electroosmosis in addition to diffusion and is shown to be a viable alternative to conventional administration routs such as oral, hypodermic and intravenous injection. In this study we investigated, experimentally and numerically, in vitro drug delivery of dexamethasone sodium phosphate to porcine skin. Different current densities, delivery durations and drug loads were investigated experimentally and introduced as boundary conditions for numerical simulations. Nernst-Planck equation was used for calculation of active substance flux through equivalent model of homogeneous hydrogel and skin layers. The obtained numerical results were in good agreement with experimental observations. A comprehensive in-silico platform, which includes appropriate numerical tools for fitting, could contribute to iontophoretic drug-delivery devices design and correct dosage and drug clearance profiles as well as to perform much faster in-silico experiments to better determine parameters and performance criteria of iontophoretic drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Computer-Aided Design of Antimicrobial Peptides

    DEFF Research Database (Denmark)

    Fjell, Christopher D.; Hancock, Robert E.W.; Jenssen, Håvard

    2010-01-01

    in antimicrobial activity. Consequently, the majority of peptides put into clinical trials have failed at some point, underlining the importance of a thorough peptide optimization. An important tool in peptide design and optimization is quantitative structure-activity relationship (QSAR) analysis, correlating...... chemical parameters with biological activities of the peptide, using statistical methods. In this review we will discuss two different in silico strategies of computer-aided antibacterial peptide design, a linear correlation model build as an extension of traditional principal component analysis (PCA......) and a non-linear artificial neural network model. Studies on structurally diverse peptides, have concluded that the PCA derived model are able to guide the antibacterial peptide design in a meaningful way, however requiring rather a high homology between the peptides in the test-set and the in silico...

  1. Methodologies Related to Computational models in View of Developing Anti-Alzheimer Drugs: An Overview.

    Science.gov (United States)

    Baheti, Kirtee; Kale, Mayura Ajay

    2018-04-17

    Since last two decades, there has been more focus on the development strategies related to Anti-Alzheimer's drug research. This may be attributed to the fact that most of the Alzheimer's cases are still mostly unknown except for a few cases, where genetic differences have been identified. With the progress of the disease, the symptoms involve intellectual deterioration, memory impairment, abnormal personality and behavioural patterns, confusion, aggression, mood swings, irritability Current therapies available for this disease give only symptomatic relief and do not focus on manipulations of biololecular processes. Nearly all the therapies to treat Alzheimer's disease, target to change the amyloid cascade which is considered to be an important in AD pathogenesis. New drug regimens are not able to keep pace with the ever-increasing understanding about dementia at molecular level. Looking into these aggravated problems, we though to put forth molecular modeling as a drug discovery approach for developing novel drugs to treat Alzheimer disease. The disease is incurable and it gets worst as it advances and finally causes death. Due to this, the design of drugs to treat this disease has become an utmost priority for research. One of the most important emerging technologies applied for this has been Computer-assisted drug design (CADD). It is a research tool that employs large scale computing strategies in an attempt to develop a model receptor site which can be used for designing of an anti-Alzheimer drug. The various models of amyloid-based calcium channels have been computationally optimized. Docking and De novo evolution are used to design the compounds. These are further subjected to absorption, distribution, metabolism, excretion and toxicity (ADMET) studies to finally bring about active compounds that are able to cross BBB. Many novel compounds have been designed which might be promising ones for the treatment of AD. The present review describes the research

  2. Organic carbamates in drug design and medicinal chemistry.

    Science.gov (United States)

    Ghosh, Arun K; Brindisi, Margherita

    2015-04-09

    The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug-target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent applications of carbamates in drug design and medicinal chemistry.

  3. "Not for human consumption": a review of emerging designer drugs.

    Science.gov (United States)

    Musselman, Megan E; Hampton, Jeremy P

    2014-07-01

    Synthetic, or "designer" drugs, are created by manipulating the chemical structures of other psychoactive drugs so that the resulting product is structurally similar but not identical to illegal psychoactive drugs. Originally developed in the 1960s as a way to evade existing drug laws, the use of designer drugs has increased dramatically over the past few years. These drugs are deceptively packaged as "research chemicals," "incense," "bath salts," or "plant food," among other names, with labels that may contain warnings such as "not for human consumption" or "not for sale to minors." The clinical effects of most new designer drugs can be described as either hallucinogenic, stimulant, or opioid-like. They may also have a combination of these effects due to designer side-chain substitutions. The easy accessibility and rapid emergence of new designer drugs have created challenges for health care providers when treating patients presenting with acute toxicity from these substances, many of which can produce significant and/or life-threatening adverse effects. Moreover, the health care provider has no way to verify the contents and/or potency of the agent ingested because it can vary between packages and distributors. Therefore, a thorough knowledge of the available designer drugs, common signs and symptoms of toxicity associated with these agents, and potential effective treatment modalities are essential to appropriately manage these patients. © 2014 Pharmacotherapy Publications, Inc.

  4. Computational Design of Animated Mechanical Characters

    Science.gov (United States)

    Coros, Stelian; Thomaszewski, Bernhard; DRZ Team Team

    2014-03-01

    A factor key to the appeal of modern CG movies and video-games is that the virtual worlds they portray place no bounds on what can be imagined. Rapid manufacturing devices hold the promise of bringing this type of freedom to our own world, by enabling the fabrication of physical objects whose appearance, deformation behaviors and motions can be precisely specified. In order to unleash the full potential of this technology however, computational design methods that create digital content suitable for fabrication need to be developed. In recent work, we presented a computational design system that allows casual users to create animated mechanical characters. Given an articulated character as input, the user designs the animated character by sketching motion curves indicating how they should move. For each motion curve, our framework creates an optimized mechanism that reproduces it as closely as possible. The resulting mechanisms are attached to the character and then connected to each other using gear trains, which are created in a semi-automated fashion. The mechanical assemblies generated with our system can be driven with a single input driver, such as a hand-operated crank or an electric motor, and they can be fabricated using rapid prototyping devices.

  5. Computational Materials Program for Alloy Design

    Science.gov (United States)

    Bozzolo, Guillermo

    2005-01-01

    The research program sponsored by this grant, "Computational Materials Program for Alloy Design", covers a period of time of enormous change in the emerging field of computational materials science. The computational materials program started with the development of the BFS method for alloys, a quantum approximate method for atomistic analysis of alloys specifically tailored to effectively deal with the current challenges in the area of atomistic modeling and to support modern experimental programs. During the grant period, the program benefited from steady growth which, as detailed below, far exceeds its original set of goals and objectives. Not surprisingly, by the end of this grant, the methodology and the computational materials program became an established force in the materials communitiy, with substantial impact in several areas. Major achievements during the duration of the grant include the completion of a Level 1 Milestone for the HITEMP program at NASA Glenn, consisting of the planning, development and organization of an international conference held at the Ohio Aerospace Institute in August of 2002, finalizing a period of rapid insertion of the methodology in the research community worlwide. The conference, attended by citizens of 17 countries representing various fields of the research community, resulted in a special issue of the leading journal in the area of applied surface science. Another element of the Level 1 Milestone was the presentation of the first version of the Alloy Design Workbench software package, currently known as "adwTools". This software package constitutes the first PC-based piece of software for atomistic simulations for both solid alloys and surfaces in the market.Dissemination of results and insertion in the materials community worldwide was a primary focus during this period. As a result, the P.I. was responsible for presenting 37 contributed talks, 19 invited talks, and publishing 71 articles in peer-reviewed journals, as

  6. Computer-aided control system design

    International Nuclear Information System (INIS)

    Lebenhaft, J.R.

    1986-01-01

    Control systems are typically implemented using conventional PID controllers, which are then tuned manually during plant commissioning to compensate for interactions between feedback loops. As plants increase in size and complexity, such controllers can fail to provide adequate process regulations. Multivariable methods can be utilized to overcome these limitations. At the Chalk River Nuclear Laboratories, modern control systems are designed and analyzed with the aid of MVPACK, a system of computer programs that appears to the user like a high-level calculator. The software package solves complicated control problems, and provides useful insight into the dynamic response and stability of multivariable systems

  7. Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

    Directory of Open Access Journals (Sweden)

    Avinaba Mukherjee

    2016-03-01

    Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug

  8. SPACEBAR: Kinematic design by computer graphics

    Science.gov (United States)

    Ricci, R. J.

    1975-01-01

    The interactive graphics computer program SPACEBAR, conceived to reduce the time and complexity associated with the development of kinematic mechanisms on the design board, was described. This program allows the direct design and analysis of mechanisms right at the terminal screen. All input variables, including linkage geometry, stiffness, and applied loading conditions, can be fed into or changed at the terminal and may be displayed in three dimensions. All mechanism configurations can be cycled through their range of travel and viewed in their various geometric positions. Output data includes geometric positioning in orthogonal coordinates of each node point in the mechanism, velocity and acceleration of the node points, and internal loads and displacements of the node points and linkages. All analysis calculations take at most a few seconds to complete. Output data can be viewed at the scope and also printed at the discretion of the user.

  9. Computational network design from functional specifications

    KAUST Repository

    Peng, Chi Han

    2016-07-11

    Connectivity and layout of underlying networks largely determine agent behavior and usage in many environments. For example, transportation networks determine the flow of traffic in a neighborhood, whereas building floorplans determine the flow of people in a workspace. Designing such networks from scratch is challenging as even local network changes can have large global effects. We investigate how to computationally create networks starting from only high-level functional specifications. Such specifications can be in the form of network density, travel time versus network length, traffic type, destination location, etc. We propose an integer programming-based approach that guarantees that the resultant networks are valid by fulfilling all the specified hard constraints and that they score favorably in terms of the objective function. We evaluate our algorithm in two different design settings, street layout and floorplans to demonstrate that diverse networks can emerge purely from high-level functional specifications.

  10. Computer design of a compact cyclotron

    International Nuclear Information System (INIS)

    Bing Wang; Huanfeng Hao; Qinggao Yao; Jinquan Zhang; Mingtao Song; Vorozhtsov, S.B.; Smirnov, V.L.; Hongwei Zhao

    2011-01-01

    Here we present results of the computer design of the structural elements of a compact cyclotron by the example of HITFiL cyclotron selected as the driving accelerator that is under construction at the Institute of Modern Physics (Lanzhou, China). In the article a complex approach to modeling of the compact cyclotron, including calculation of electromagnetic fields of the structural elements and beam dynamics calculations, is described. The existing design data on the axial injection, magnetic, acceleration and extraction systems of the cyclotron are used as a starting point in the simulation. Some of the upgrades of the cyclotron structural elements were proposed, which led to substantial improvement of the beam quality and transmission

  11. Design and Synthesis of Epigenetic Drugs

    DEFF Research Database (Denmark)

    Leurs, Ulrike

    2014-01-01

    of histone- and DNA-modifying enzymes can lead to the development of diseases such as cancer. The histone demethylases of the KDM4 family have been implicated in a wide range of diseases, and are hence important drug targets. KDM4s belong to the bigger family of 2-OG oxygenases, an enzyme class sharing high...

  12. Computer architecture fundamentals and principles of computer design

    CERN Document Server

    Dumas II, Joseph D

    2005-01-01

    Introduction to Computer ArchitectureWhat is Computer Architecture?Architecture vs. ImplementationBrief History of Computer SystemsThe First GenerationThe Second GenerationThe Third GenerationThe Fourth GenerationModern Computers - The Fifth GenerationTypes of Computer SystemsSingle Processor SystemsParallel Processing SystemsSpecial ArchitecturesQuality of Computer SystemsGenerality and ApplicabilityEase of UseExpandabilityCompatibilityReliabilitySuccess and Failure of Computer Architectures and ImplementationsQuality and the Perception of QualityCost IssuesArchitectural Openness, Market Timi

  13. Cloud Computing for Mission Design and Operations

    Science.gov (United States)

    Arrieta, Juan; Attiyah, Amy; Beswick, Robert; Gerasimantos, Dimitrios

    2012-01-01

    The space mission design and operations community already recognizes the value of cloud computing and virtualization. However, natural and valid concerns, like security, privacy, up-time, and vendor lock-in, have prevented a more widespread and expedited adoption into official workflows. In the interest of alleviating these concerns, we propose a series of guidelines for internally deploying a resource-oriented hub of data and algorithms. These guidelines provide a roadmap for implementing an architecture inspired in the cloud computing model: associative, elastic, semantical, interconnected, and adaptive. The architecture can be summarized as exposing data and algorithms as resource-oriented Web services, coordinated via messaging, and running on virtual machines; it is simple, and based on widely adopted standards, protocols, and tools. The architecture may help reduce common sources of complexity intrinsic to data-driven, collaborative interactions and, most importantly, it may provide the means for teams and agencies to evaluate the cloud computing model in their specific context, with minimal infrastructure changes, and before committing to a specific cloud services provider.

  14. Computational Fluid Dynamics in Ventilation Design

    DEFF Research Database (Denmark)

    Nielsen, Peter V.

    2008-01-01

    This paper is based on the new REHVA Guidebook Computational Fluid  Dynamics in Ventilation Design (Nielsen et al. 2007) written by Peter V. Nielsen, Francis(Nielsen 2007) written by Peter V. Nielsen, Francis Allard, Hazim B. Awbi, Lars Davidson and Alois Schälin. The guidebook is made for people....... The guidebook introduces rules for good quality prediction work, and it is the purpose of the guidebook to improve the technical level of CFD work in ventilation.......This paper is based on the new REHVA Guidebook Computational Fluid  Dynamics in Ventilation Design (Nielsen et al. 2007) written by Peter V. Nielsen, Francis(Nielsen 2007) written by Peter V. Nielsen, Francis Allard, Hazim B. Awbi, Lars Davidson and Alois Schälin. The guidebook is made for people...... who need to use and discuss results based on CFD predictions, and it gives insight into the subject for those who are not used to work with CFD. The guidebook is also written for people working with CFD who have to be more aware of how this numerical method is applied in the area of ventilation...

  15. Computer aided materials design; Keisanki zairyo sekkei

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The questionnaire survey on the computer aided materials design (CAMD), and the survey of current domestic and overseas software concerned were carried out to clarify developmental issues. The current elementary technology of CAMD was also surveyed to study its several problems caused with a progress of material design technology due to drastic diffusion of CAMD. This project aims at establishment of a new demanded software, computer chemistry, focusing attention on functional materials such as catalyst, polymer and non-linear electronic materials. Microscopic simulation technology was mainly surveyed in fiscal 1996. Although some fruitful results have been obtained in the fields of medical and agricultural chemicals, organic compounds, proteins, catalysts and electronic materials, such some problems are pointed out as `CAMD cannot handle an actual size of the target system` and `commercially available software are very expensive.` Reliable tool development as elementary technology, and the verification of its applications are thus required. Meso-dynamics, polymers, surface reaction and integrated technological environment attract users` attention. 27 refs., 16 figs., 2 tabs.

  16. Dynamic Docking: A Paradigm Shift in Computational Drug Discovery

    Directory of Open Access Journals (Sweden)

    Dario Gioia

    2017-11-01

    Full Text Available Molecular docking is the methodology of choice for studying in silico protein-ligand binding and for prioritizing compounds to discover new lead candidates. Traditional docking simulations suffer from major limitations, mostly related to the static or semi-flexible treatment of ligands and targets. They also neglect solvation and entropic effects, which strongly limits their predictive power. During the last decade, methods based on full atomistic molecular dynamics (MD have emerged as a valid alternative for simulating macromolecular complexes. In principle, compared to traditional docking, MD allows the full exploration of drug-target recognition and binding from both the mechanistic and energetic points of view (dynamic docking. Binding and unbinding kinetic constants can also be determined. While dynamic docking is still too computationally expensive to be routinely used in fast-paced drug discovery programs, the advent of faster computing architectures and advanced simulation methodologies are changing this scenario. It is feasible that dynamic docking will replace static docking approaches in the near future, leading to a major paradigm shift in in silico drug discovery. Against this background, we review the key achievements that have paved the way for this progress.

  17. Ecological Interface Design for Computer Network Defense.

    Science.gov (United States)

    Bennett, Kevin B; Bryant, Adam; Sushereba, Christen

    2018-05-01

    A prototype ecological interface for computer network defense (CND) was developed. Concerns about CND run high. Although there is a vast literature on CND, there is some indication that this research is not being translated into operational contexts. Part of the reason may be that CND has historically been treated as a strictly technical problem, rather than as a socio-technical problem. The cognitive systems engineering (CSE)/ecological interface design (EID) framework was used in the analysis and design of the prototype interface. A brief overview of CSE/EID is provided. EID principles of design (i.e., direct perception, direct manipulation and visual momentum) are described and illustrated through concrete examples from the ecological interface. Key features of the ecological interface include (a) a wide variety of alternative visual displays, (b) controls that allow easy, dynamic reconfiguration of these displays, (c) visual highlighting of functionally related information across displays, (d) control mechanisms to selectively filter massive data sets, and (e) the capability for easy expansion. Cyber attacks from a well-known data set are illustrated through screen shots. CND support needs to be developed with a triadic focus (i.e., humans interacting with technology to accomplish work) if it is to be effective. Iterative design and formal evaluation is also required. The discipline of human factors has a long tradition of success on both counts; it is time that HF became fully involved in CND. Direct application in supporting cyber analysts.

  18. 7th International Conference on Design Computing and Cognition

    CERN Document Server

    2017-01-01

    This book gathers the peer-reviewed and revised versions of papers from the Seventh International Conference on Design Computing and Cognition (DCC'16), held at Northwestern University, Evanston (Chicago), USA, from 27–29 June 2016. The material presented here reflects cutting-edge design research with a focus on artificial intelligence, cognitive science and computational theories. The papers are grouped under the following nine headings, describing advances in theory and applications alike and demonstrating the depth and breadth of design computing and design cognition: Design Creativity; Design Cognition - Design Approaches; Design Support; Design Grammars; Design Cognition - Design Behaviors; Design Processes; Design Synthesis; Design Activity and Design Knowledge. The book will be of particular interest to researchers, developers and users of advanced computation in design across all disciplines, and to all readers who need to gain a better understanding of designing.

  19. Emerging Computational Methods for the Rational Discovery of Allosteric Drugs.

    Science.gov (United States)

    Wagner, Jeffrey R; Lee, Christopher T; Durrant, Jacob D; Malmstrom, Robert D; Feher, Victoria A; Amaro, Rommie E

    2016-06-08

    Allosteric drug development holds promise for delivering medicines that are more selective and less toxic than those that target orthosteric sites. To date, the discovery of allosteric binding sites and lead compounds has been mostly serendipitous, achieved through high-throughput screening. Over the past decade, structural data has become more readily available for larger protein systems and more membrane protein classes (e.g., GPCRs and ion channels), which are common allosteric drug targets. In parallel, improved simulation methods now provide better atomistic understanding of the protein dynamics and cooperative motions that are critical to allosteric mechanisms. As a result of these advances, the field of predictive allosteric drug development is now on the cusp of a new era of rational structure-based computational methods. Here, we review algorithms that predict allosteric sites based on sequence data and molecular dynamics simulations, describe tools that assess the druggability of these pockets, and discuss how Markov state models and topology analyses provide insight into the relationship between protein dynamics and allosteric drug binding. In each section, we first provide an overview of the various method classes before describing relevant algorithms and software packages.

  20. Computational modeling of drug transport across the in vitro cornea.

    Science.gov (United States)

    Pak, Joseph; Chen, Z J; Sun, Kay; Przekwas, Andrzej; Walenga, Ross; Fan, Jianghong

    2018-01-01

    A novel quasi-3D (Q3D) modeling approach was developed to model networks of one dimensional structures like tubes and vessels common in human anatomy such as vascular and lymphatic systems, neural networks, and respiratory airways. Instead of a branching network of the same tissue type, this approach was extended to model an interconnected stack of different corneal tissue layers with membrane junction conditions assigned between the tissues. The multi-laminate structure of the cornea presents a unique barrier design and opportunity for investigation using Q3D modeling. A Q3D model of an in vitro rabbit cornea was created to simulate the drug transport across the cornea, accounting for transcellular and paracellular pathways of passive and convective drug transport as well as physicochemistry of lipophilic partitioning and protein binding. Lipophilic Rhodamine B and hydrophilic fluorescein were used as drug analogs. The model predictions for both hydrophilic and lipophilic tracers were able to match the experimental measurements along with the sharp discontinuities at the epithelium-stroma and stroma-endothelium interfaces. This new modeling approach was successfully applied towards pharmacokinetic modeling for use in topical ophthalmic drug design. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Computer Based Training Authors' and Designers' training

    Directory of Open Access Journals (Sweden)

    Frédéric GODET

    2016-03-01

    Full Text Available This communication, through couple of studies driven since 10 years, tries to show how important is the training of authors in Computer Based Training (CBT. We submit here an approach to prepare designers mastering Interactive Multimedia modules in this domain. Which institutions are really dedicating their efforts in training authors and designers in this area of CBTs? Television devices and broadcast organisations offered since year 60s' a first support for Distance Learning. New media, New Information and Communication Technologies (NICT allowed several public and private organisations to start Distance Learning projects. As usual some of them met their training objectives, other of them failed. Did their really failed? Currently, nobody has the right answer. Today, we do not have enough efficient tools allowing us to evaluate trainees' acquisition in a short term view. Training evaluation needs more than 10 to 20 years of elapsed time to bring reliable measures. Nevertheless, given the high investments already done in this area, we cannot wait until the final results of the pedagogical evaluation. A lot of analyses showed relevant issues which can be used as directions for CBTs authors and designers training. Warning - Our studies and the derived conclusions are mainly based on projects driven in the field. We additionally bring our several years experience in the training of movie film authors in the design of interactive multimedia products. Some of our examples are extracting from vocational training projects where we were involved in all development phases from the analysis of needs to the evaluation of the acquisition within the trainee's / employee job's. Obviously, we cannot bring and exhaustive approach in this domain where a lot of parameters are involved as frame for the CBT interactive multimedia modules authors' and designers' training.

  2. 6th International Conference on Design Computing and Cognition

    CERN Document Server

    Hanna, Sean

    2015-01-01

    This book details the state-of-the-art of research and development in design computing and design cognition. It features more than 35 papers that were presented at the Sixth International Conference on Design Computing and Cognition, DCC’14, held at University College, London, UK. Inside, readers will find the work of expert researchers and practitioners that explores both advances in theory and application as well as demonstrates the depth and breadth of design computing and design cognition. This interdisciplinary coverage, which includes material from international research groups, examines design synthesis, design cognition, design creativity, design processes, design theory, design grammars, design support, and design ideation. Overall, the papers provide a bridge between design computing and design cognition. The confluence of these two fields continues to build the foundation for further advances and leads to an increased understanding of design as an activity whose influence continues to spread. ...

  3. Designer Drugs: A Review of Literature Abdulsallam Bakdash

    Directory of Open Access Journals (Sweden)

    Abdulsallam Bakdash

    2015-05-01

    Full Text Available A new phenomenon in the drug market has appeared in recent years: there has been an increase in the number and types of designer drugs. A massive influx of these structural and/or functional analogs of controlled substances has resulted in an increase in their marketing and abuse. At present, these drugs are significantly more widely available compared to previous years because they are relatively inexpensive and marketed as being safer than classic drugs of abuse. The most important factor in the spread of designer drugs is that the majority of these substances are undetectable as drugs or illegal drugs in standard drug testing procedures. The biological effects of these substances are largely unknown to both users and medical scientists. However, most known cases of abuse have shown serious and dangerous physical and psychological reactions in users. The manufacturing and marketing of designer drugs presents a major challenge for specialist sectors, especially laboratories that have to test these substances. This highlights the important role of drugcontrol institutions and regulatory and legislative bodies to determine the legal status of these drugs, which are designed and marketed - mostly through the internet - as being legal. All of these factors make it incumbent upon these sectors to form a unified goal and strategy to control these substances and prevent their spread. This review provides fundamental information about designer drugs. This will provide an accurate overview of their status, and will aid future work to develop a regulatory and legislative strategy to combat their manufacture, marketing, and use.

  4. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

    Science.gov (United States)

    Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

    2018-02-01

    For a drug, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

  5. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

    Directory of Open Access Journals (Sweden)

    Hongbin Yang

    2018-02-01

    Full Text Available During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

  6. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts.

    Science.gov (United States)

    Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

    2018-01-01

    During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

  7. Microcrystalline identification of selected designer drugs.

    Science.gov (United States)

    Elie, Leonie; Baron, Mark; Croxton, Ruth; Elie, Mathieu

    2012-01-10

    A microcrystalline test for the detection of 4-methylmethcathinone (mephedrone), benzylpiperazine (BZP) and 5,6-methylenedioxy-2-aminoindane (MDAI) using aqueous solutions of mercury chloride is described. Each of the compounds investigated formed specific drug-reagent crystals within minutes. The uniqueness of the test was confirmed by comparison of the microcrystalline response to that of other psychoactive stimulants and a common cutting agent. The limit of detection and cut-off levels for reference standards were established to 3 g/L and 5 g/L for mephedrone, 0.5 g/L for MDAI and 0.2 g/L and 0.3 g/L for BZP, respectively. Various mixtures of standards of either mephedrone, BZP or MDAI combined with caffeine were investigated for their microcrystalline response. Results showed that simultaneous detection of drug and cutting agent was possible with the concentrations tested but were dependant on the ratio of drug to cutting agent. BZP could be detected alongside caffeine from as low as 20% (v/v), MDAI from 40% (v/v) and mephedrone from 50% (v/v) and higher. Finally, seven samples of online purchased 'legal highs' were analysed using the developed test and the findings were compared to FTIR and GC-MS results. It was shown that 6 out of 7 samples did not contain the advertised active ingredient. Five samples consisted of BZP, caffeine and 1-[3-(trifluoromethyl)phenyl]piperazine (3-TFMPP). The microcrystalline tests carried out on these samples showed positive results for both BZP and caffeine without interference from other substances present. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Emergency Physicians' Knowledge of Cannabinoid Designer Drugs

    Directory of Open Access Journals (Sweden)

    Patrick M Lank

    2013-09-01

    Full Text Available Introduction: The use of synthetic drugs of abuse in the United States has grown in the last few years, with little information available on how much physicians know about these drugs and how they are treating patients using them. The objective of this study was to assess emergency physician (EP knowledge of synthetic cannabinoids (SC.Methods: A self-administered internet-based survey of resident and attending EPs at a large urban emergency department (ED was administered to assess familiarity with the terms Spice or K2 and basic knowledge of SC, and to describe some practice patterns when managing SC intoxication in the ED.Results: Of the 83 physicians invited to participate, 73 (88% completed surveys. The terms “Spice” and “K2” for SC were known to 25/73 (34% and 36/73 (49% of respondents. Knowledge of SC came most commonly (72% from non-medical sources, with lay publications and the internet providing most respondents with information. Among those with previous knowledge of synthetic cannabinoids, 25% were not aware that SC are synthetic drugs, and 17% did not know they are chemically most similar to marijuana. Among all participants, 80% felt unprepared caring for a patient in the ED who had used synthetic cannabinoids.Conclusion: Clinically active EPs are unfamiliar with synthetic cannabinoids. Even those who stated they had heard of synthetic cannabinoids answered poorly on basic knowledge questions. More education is needed among EPs of all ages and levels of training on synthetic cannabinoids. [West J Emerg Med. 2013;14(5:467–470.

  9. RECENT ADVANCES TOWARDS THE RATIONAL DESIGN OF PEPTIDE DRUGS

    OpenAIRE

    YEŞİLADA, Akgül; ÖZKANLI, Fügen

    2004-01-01

    In this review, after a short introduction to definition and physiological roles of regulatory peptides, problems faced during the development of peptide drugs, studies directed to solve these problems and rational design of peptide drugs with special emphesis on peptidomimetics are mentioned

  10. Computational Tools for RF Structure Design

    CERN Document Server

    Jensen, E

    2004-01-01

    The Finite Differences Method and the Finite Element Method are the two principally employed numerical methods in modern RF field simulation programs. The basic ideas behind these methods are explained, with regard to available simulation programs. We then go through a list of characteristic parameters of RF structures, explaining how they can be calculated using these tools. With the help of these parameters, we introduce the frequency-domain and the time-domain calculations, leading to impedances and wake-fields, respectively. Subsequently, we present some readily available computer programs, which are in use for RF structure design, stressing their distinctive features and limitations. One final example benchmarks the precision of different codes for calculating the eigenfrequency and Q of a simple cavity resonator.

  11. Optical design teaching by computing graphic methods

    Science.gov (United States)

    Vazquez-Molini, D.; Muñoz-Luna, J.; Fernandez-Balbuena, A. A.; Garcia-Botella, A.; Belloni, P.; Alda, J.

    2012-10-01

    One of the key challenges in the teaching of Optics is that students need to know not only the math of the optical design, but also, and more important, to grasp and understand the optics in a three-dimensional space. Having a clear image of the problem to solve is the first step in order to begin to solve that problem. Therefore to achieve that the students not only must know the equation of refraction law but they have also to understand how the main parameters of this law are interacting among them. This should be a major goal in the teaching course. Optical graphic methods are a valuable tool in this way since they have the advantage of visual information and the accuracy of a computer calculation.

  12. Computer-aided design for metabolic engineering.

    Science.gov (United States)

    Fernández-Castané, Alfred; Fehér, Tamás; Carbonell, Pablo; Pauthenier, Cyrille; Faulon, Jean-Loup

    2014-12-20

    The development and application of biotechnology-based strategies has had a great socio-economical impact and is likely to play a crucial role in the foundation of more sustainable and efficient industrial processes. Within biotechnology, metabolic engineering aims at the directed improvement of cellular properties, often with the goal of synthesizing a target chemical compound. The use of computer-aided design (CAD) tools, along with the continuously emerging advanced genetic engineering techniques have allowed metabolic engineering to broaden and streamline the process of heterologous compound-production. In this work, we review the CAD tools available for metabolic engineering with an emphasis, on retrosynthesis methodologies. Recent advances in genetic engineering strategies for pathway implementation and optimization are also reviewed as well as a range of bionalytical tools to validate in silico predictions. A case study applying retrosynthesis is presented as an experimental verification of the output from Retropath, the first complete automated computational pipeline applicable to metabolic engineering. Applying this CAD pipeline, together with genetic reassembly and optimization of culture conditions led to improved production of the plant flavonoid pinocembrin. Coupling CAD tools with advanced genetic engineering strategies and bioprocess optimization is crucial for enhanced product yields and will be of great value for the development of non-natural products through sustainable biotechnological processes. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

    Directory of Open Access Journals (Sweden)

    Charles H. Williams

    2011-04-01

    Full Text Available In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design.

  14. Computational toxicology: Its essential role in reducing drug attrition.

    Science.gov (United States)

    Naven, R T; Louise-May, S

    2015-12-01

    Predictive toxicology plays a critical role in reducing the failure rate of new drugs in pharmaceutical research and development. Despite recent gains in our understanding of drug-induced toxicity, however, it is urgent that the utility and limitations of our current predictive tools be determined in order to identify gaps in our understanding of mechanistic and chemical toxicology. Using recently published computational regression analyses of in vitro and in vivo toxicology data, it will be demonstrated that significant gaps remain in early safety screening paradigms. More strategic analyses of these data sets will allow for a better understanding of their domain of applicability and help identify those compounds that cause significant in vivo toxicity but which are currently mis-predicted by in silico and in vitro models. These 'outliers' and falsely predicted compounds are metaphorical lighthouses that shine light on existing toxicological knowledge gaps, and it is essential that these compounds are investigated if attrition is to be reduced significantly in the future. As such, the modern computational toxicologist is more productively engaged in understanding these gaps and driving investigative toxicology towards addressing them. © The Author(s) 2015.

  15. Electronic circuit design with HEP computational tools

    International Nuclear Information System (INIS)

    Vaz, Mario

    1996-01-01

    CPSPICE is an electronic circuit statistical simulation program developed to run in a parallel environment under UNIX operating system and TCP/IP communications protocol, using CPS - Cooperative Processes Software , SPICE program and CERNLIB software package. It is part of a set of tools being develop, intended to help electronic engineers to design, model and simulate complex systems and circuits for High Energy Physics detectors, based on statistical methods, using the same software and methodology used by HEP physicists for data analysis. CPSPICE simulates electronic circuits by Monte Carlo method, through several different processes running simultaneously SPICE in UNIX parallel computers or workstation farms. Data transfer between CPS processes for a modified version of SPICE2G6 is done by RAM memory, but can also be done through hard disk files if no source files are available for the simulator, and for bigger simulation outputs files. Simulation results are written in a HBOOK file as a NTUPLE, to be examined by HBOOK in batch model or graphics, and analyzed by statistical procedures available. The HBOOK file be stored on hard disk for small amount of data, or into Exabyte tape file for large amount of data. HEP tools also helps circuit or component modeling, like MINUT program from CERNLIB, that implements Nelder and Mead Simplex and Gradient with or without derivatives algorithms, and can be used for design optimization.This paper presents CPSPICE program implementation. The scheme adopted is suitable to make parallel other electronic circuit simulators. (author)

  16. The design of drugs for HIV and HCV.

    Science.gov (United States)

    De Clercq, Erik

    2007-12-01

    Since the discovery of the human immunodeficiency virus (HIV) in 1983, dramatic progress has been made in the development of novel antiviral drugs. The HIV epidemic fuelled the development of new antiviral drug classes, which are now combined to provide highly active antiretroviral therapies. The need for the treatment of hepatitis C virus (HCV), which was discovered in 1989, has also provided considerable impetus for the development of new classes of antiviral drugs, and future treatment strategies for chronic HCV might involve combination regimens that are analogous to those currently used for HIV. By considering the drug targets in the different stages of the life cycle of these two viruses, this article presents aspects of the history, medicinal chemistry and mechanisms of action of approved and investigational drugs for HIV and HCV, and highlights general lessons learned from anti-HIV-drug design that could be applied to HCV.

  17. Development of a computer design system for HVAC

    International Nuclear Information System (INIS)

    Miyazaki, Y.; Yotsuya, M.; Hasegawa, M.

    1993-01-01

    The development of a computer design system for HVAC (Heating, Ventilating and Air Conditioning) system is presented in this paper. It supports the air conditioning design for a nuclear power plant and a reprocessing plant. This system integrates various computer design systems which were developed separately for the various design phases of HVAC. the purposes include centralizing the HVAC data, optimizing design, and reducing the designing time. The centralized HVAC data are managed by a DBMS (Data Base Management System). The DBMS separates the computer design system into a calculation module and the data. The design system can thus be expanded easily in the future. 2 figs

  18. Design of an Implantable Device for Ocular Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jae-Hwan Lee

    2012-01-01

    Full Text Available Ocular diseases, such as, glaucoma, age-related macular degeneration (AMD, diabetic retinopathy, and retinitis pigmentosa require drug management in order to prevent blindness and affecting million of adults in USA and worldwide. There is an increasing need to develop devices for drug delivery to address ocular diseases. This study focuses on the design, simulation, and development of an implantable ocular drug delivery device consisting of micro-/nanochannels embedded between top and bottom covers with a drug reservoir made from polydimethylsiloxane (PDMS which is silicon-based organic and biodegradable polymer. Several simulations were carried out with six different micro-channel configurations in order to see the feasibility for ocular drug delivery applications. Based on the results obtained, channel design of osmotic I and osmotic II satisfied the diffusion rates required for ocular drug delivery. Finally, a prototype illustrating the three components of the drug delivery design is presented. In the future, the device will be tested for its functionality and diffusion characteristics.

  19. Physics and Its Interfaces with Medicinal Chemistry and Drug Design

    Science.gov (United States)

    Santos, Ricardo N.; Andricopulo, Adriano D.

    2013-08-01

    Medicinal chemistry is a multidisciplinary subject that integrates knowledge from a variety of fields of science, including, but not limited to, chemistry, biology, and physics. The area of drug design involves the cooperative work of scientists with a diverse range of backgrounds and technical skills, trying to tackle complex problems using an integration of approaches and methods. One important contribution to this field comes from physics through studies that attempt to identify and quantify the molecular interactions between small molecules (drugs) and biological targets (receptors), such as the forces that govern the interactions, the thermodynamics of the drug-receptor interactions, and so on. In this context, the interfaces of physics, medicinal chemistry, and drug design are of vital importance for the development of drugs that not only have the right chemistry but also the right intermolecular properties to interact at the macromolecular level, providing useful information about the principles and molecular mechanisms underlying the therapeutic action of drugs. This article highlights some of the most important connections between physics and medicinal chemistry in the design of new drugs.

  20. Intelligent Support for a Computer Aided Design Optimisation Cycle

    OpenAIRE

    B. Dolšak; M. Novak; J. Kaljun

    2006-01-01

    It is becoming more and more evident that  adding intelligence  to existing computer aids, such as computer aided design systems, can lead to significant improvements in the effective and reliable performance of various engineering tasks, including design optimisation. This paper presents three different intelligent modules to be applied within a computer aided design optimisation cycle to enable more intelligent and less experience-dependent design performance. 

  1. Instrument design optimization with computational methods

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Michael H. [Old Dominion Univ., Norfolk, VA (United States)

    2017-08-01

    Using Finite Element Analysis to approximate the solution of differential equations, two different instruments in experimental Hall C at the Thomas Jefferson National Accelerator Facility are analyzed. The time dependence of density uctuations from the liquid hydrogen (LH2) target used in the Qweak experiment (2011-2012) are studied with Computational Fluid Dynamics (CFD) and the simulation results compared to data from the experiment. The 2.5 kW liquid hydrogen target was the highest power LH2 target in the world and the first to be designed with CFD at Jefferson Lab. The first complete magnetic field simulation of the Super High Momentum Spectrometer (SHMS) is presented with a focus on primary electron beam deflection downstream of the target. The SHMS consists of a superconducting horizontal bending magnet (HB) and three superconducting quadrupole magnets. The HB allows particles scattered at an angle of 5:5 deg to the beam line to be steered into the quadrupole magnets which make up the optics of the spectrometer. Without mitigation, remnant fields from the SHMS may steer the unscattered beam outside of the acceptable envelope on the beam dump and limit beam operations at small scattering angles. A solution is proposed using optimal placement of a minimal amount of shielding iron around the beam line.

  2. A CAD (Classroom Assessment Design) of a Computer Programming Course

    Science.gov (United States)

    Hawi, Nazir S.

    2012-01-01

    This paper presents a CAD (classroom assessment design) of an entry-level undergraduate computer programming course "Computer Programming I". CAD has been the product of a long experience in teaching computer programming courses including teaching "Computer Programming I" 22 times. Each semester, CAD is evaluated and modified…

  3. DEFACTO: A Design Environment for Adaptive Computing Technology

    National Research Council Canada - National Science Library

    Hall, Mary

    2003-01-01

    This report describes the activities of the DEFACTO project, a Design Environment for Adaptive Computing Technology funded under the DARPA Adaptive Computing Systems and Just-In-Time-Hardware programs...

  4. The Use of Computer Graphics in the Design Process.

    Science.gov (United States)

    Palazzi, Maria

    This master's thesis examines applications of computer technology to the field of industrial design and ways in which technology can transform the traditional process. Following a statement of the problem, the history and applications of the fields of computer graphics and industrial design are reviewed. The traditional industrial design process…

  5. Molecular Thermodynamic Modeling and Design of Microencapsulation Systems for Drug Delivery

    DEFF Research Database (Denmark)

    Abildskov, Jens; O’Connell, John P.

    2011-01-01

    is based on fundamental thermodynamic relations and group contributions to properties of pure species (solvent, active ingredient and polymer) and their mixtures. The method is intended for pharmaceuticals with complex molecular structures, for which limited experimental information is known. Case studies......A systematic design strategy is given for computer-aided design of microparticle drug-delivery systems produced by solvent evaporation. In particular, design of solvents, polymer material, and external phase composition are considered for the case when the active ingredient is known. The procedure...... of solvent design are given....

  6. HF filter design and computer simulation

    CERN Document Server

    Rhea, Randall W

    1994-01-01

    A book for engineers who design and build filters of all types, including lumped element, coaxial, helical, dielectric resonator, stripline and microstrip types. A thorough review of classic and modern filter design techniques, containing extensive practical design information of passband characteristics, topologies and transformations, component effects and matching. An excellent text for the design and construction of microstrip filters.

  7. Early phase drug discovery: cheminformatics and computational techniques in identifying lead series.

    Science.gov (United States)

    Duffy, Bryan C; Zhu, Lei; Decornez, Hélène; Kitchen, Douglas B

    2012-09-15

    Early drug discovery processes rely on hit finding procedures followed by extensive experimental confirmation in order to select high priority hit series which then undergo further scrutiny in hit-to-lead studies. The experimental cost and the risk associated with poor selection of lead series can be greatly reduced by the use of many different computational and cheminformatic techniques to sort and prioritize compounds. We describe the steps in typical hit identification and hit-to-lead programs and then describe how cheminformatic analysis assists this process. In particular, scaffold analysis, clustering and property calculations assist in the design of high-throughput screening libraries, the early analysis of hits and then organizing compounds into series for their progression from hits to leads. Additionally, these computational tools can be used in virtual screening to design hit-finding libraries and as procedures to help with early SAR exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Molecular docking as a popular tool in drug design, an in silico travel

    Directory of Open Access Journals (Sweden)

    de Ruyck J

    2016-06-01

    Full Text Available Jerome de Ruyck, Guillaume Brysbaert, Ralf Blossey, Marc F Lensink University Lille, CNRS UMR8576 UGSF, Lille, FranceAbstract: New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism- or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Second, we present recent advances in anti-infectious agents' synthesis driven by structural insights. At the end, we focus on larger biological complexes made by protein–protein interactions and discuss their relevance in drug design. This review provides information on how these large systems, even in the presence of the solvent, can be investigated with the outlook of drug discovery.Keywords: structure-based drug design, protein–protein docking, quaternary structure prediction, residue interaction networks, RINs, water position

  9. Brain architecture: a design for natural computation.

    Science.gov (United States)

    Kaiser, Marcus

    2007-12-15

    Fifty years ago, John von Neumann compared the architecture of the brain with that of the computers he invented and which are still in use today. In those days, the organization of computers was based on concepts of brain organization. Here, we give an update on current results on the global organization of neural systems. For neural systems, we outline how the spatial and topological architecture of neuronal and cortical networks facilitates robustness against failures, fast processing and balanced network activation. Finally, we discuss mechanisms of self-organization for such architectures. After all, the organization of the brain might again inspire computer architecture.

  10. Design of a modular digital computer system, DRL 4. [for meeting future requirements of spaceborne computers

    Science.gov (United States)

    1972-01-01

    The design is reported of an advanced modular computer system designated the Automatically Reconfigurable Modular Multiprocessor System, which anticipates requirements for higher computing capacity and reliability for future spaceborne computers. Subjects discussed include: an overview of the architecture, mission analysis, synchronous and nonsynchronous scheduling control, reliability, and data transmission.

  11. Interaction of anthraquinone anti-cancer drugs with DNA:Experimental and computational quantum chemical study

    Science.gov (United States)

    Al-Otaibi, Jamelah S.; Teesdale Spittle, Paul; El Gogary, Tarek M.

    2017-01-01

    Anthraquinones form the basis of several anticancer drugs. Anthraquinones anticancer drugs carry out their cytotoxic activities through their interaction with DNA, and inhibition of topoisomerase II activity. Anthraquinones (AQ4 and AQ4H) were synthesized and studied along with 1,4-DAAQ by computational and experimental tools. The purpose of this study is to shade more light on mechanism of interaction between anthraquinone DNA affinic agents and different types of DNA. This study will lead to gain of information useful for drug design and development. Molecular structures were optimized using DFT B3LYP/6-31 + G(d). Depending on intramolecular hydrogen bonding interactions two conformers of AQ4 were detected and computed as 25.667 kcal/mol apart. Molecular reactivity of the anthraquinone compounds was explored using global and condensed descriptors (electrophilicity and Fukui functions). Molecular docking studies for the inhibition of CDK2 and DNA binding were carried out to explore the anti cancer potency of these drugs. NMR and UV-VIS electronic absorption spectra of anthraquinones/DNA were investigated at the physiological pH. The interaction of the three anthraquinones (AQ4, AQ4H and 1,4-DAAQ) were studied with three DNA (calf thymus DNA, (Poly[dA].Poly[dT]) and (Poly[dG].Poly[dC]). NMR study shows a qualitative pattern of drug/DNA interaction in terms of band shift and broadening. UV-VIS electronic absorption spectra were employed to measure the affinity constants of drug/DNA binding using Scatchard analysis.

  12. New or improved computational methods and advanced reactor design

    International Nuclear Information System (INIS)

    Nakagawa, Masayuki; Takeda, Toshikazu; Ushio, Tadashi

    1997-01-01

    Nuclear computational method has been studied continuously up to date, as a fundamental technology supporting the nuclear development. At present, research on computational method according to new theory and the calculating method thought to be difficult to practise are also continued actively to find new development due to splendid improvement of features of computer. In Japan, many light water type reactors are now in operations, new computational methods are induced for nuclear design, and a lot of efforts are concentrated for intending to more improvement of economics and safety. In this paper, some new research results on the nuclear computational methods and their application to nuclear design of the reactor were described for introducing recent trend of the nuclear design of the reactor. 1) Advancement of the computational method, 2) Reactor core design and management of the light water reactor, and 3) Nuclear design of the fast reactor. (G.K.)

  13. Brain architecture: A design for natural computation

    OpenAIRE

    Kaiser, Marcus

    2008-01-01

    Fifty years ago, John von Neumann compared the architecture of the brain with that of computers that he invented and which is still in use today. In those days, the organisation of computers was based on concepts of brain organisation. Here, we give an update on current results on the global organisation of neural systems. For neural systems, we outline how the spatial and topological architecture of neuronal and cortical networks facilitates robustness against failures, fast processing, and ...

  14. Designing an intuitive web application for drug discovery scientists.

    Science.gov (United States)

    Karamanis, Nikiforos; Pignatelli, Miguel; Carvalho-Silva, Denise; Rowland, Francis; Cham, Jennifer A; Dunham, Ian

    2018-01-11

    We discuss how we designed the Open Targets Platform (www.targetvalidation.org), an intuitive application for bench scientists working in early drug discovery. To meet the needs of our users, we applied lean user experience (UX) design methods: we started engaging with users very early and carried out research, design and evaluation activities within an iterative development process. We also emphasize the collaborative nature of applying lean UX design, which we believe is a foundation for success in this and many other scientific projects. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Computers as Components Principles of Embedded Computing System Design

    CERN Document Server

    Wolf, Wayne

    2008-01-01

    This book was the first to bring essential knowledge on embedded systems technology and techniques under a single cover. This second edition has been updated to the state-of-the-art by reworking and expanding performance analysis with more examples and exercises, and coverage of electronic systems now focuses on the latest applications. Researchers, students, and savvy professionals schooled in hardware or software design, will value Wayne Wolf's integrated engineering design approach.The second edition gives a more comprehensive view of multiprocessors including VLIW and superscalar archite

  16. Quantum mechanics implementation in drug-design workflows: does it really help?

    Science.gov (United States)

    Arodola, Olayide A; Soliman, Mahmoud Es

    2017-01-01

    The pharmaceutical industry is progressively operating in an era where development costs are constantly under pressure, higher percentages of drugs are demanded, and the drug-discovery process is a trial-and-error run. The profit that flows in with the discovery of new drugs has always been the motivation for the industry to keep up the pace and keep abreast with the endless demand for medicines. The process of finding a molecule that binds to the target protein using in silico tools has made computational chemistry a valuable tool in drug discovery in both academic research and pharmaceutical industry. However, the complexity of many protein-ligand interactions challenges the accuracy and efficiency of the commonly used empirical methods. The usefulness of quantum mechanics (QM) in drug-protein interaction cannot be overemphasized; however, this approach has little significance in some empirical methods. In this review, we discuss recent developments in, and application of, QM to medically relevant biomolecules. We critically discuss the different types of QM-based methods and their proposed application to incorporating them into drug-design and -discovery workflows while trying to answer a critical question: are QM-based methods of real help in drug-design and -discovery research and industry?

  17. Connecting drug delivery reality to smart materials design.

    Science.gov (United States)

    Grainger, David W

    2013-09-15

    Inflated claims to both design and mechanistic novelty in drug delivery and imaging systems, including most nanotechnologies, are not supported by the generally poor translation of these systems to clinical efficacy. The "form begets function" design paradigm is seductive but perhaps over-simplistic in translation to pharmaceutical efficacy. Most innovations show few clinically important distinctions in their therapeutic benefits in relevant preclinical disease and delivery models, despite frequent claims to the contrary. Long-standing challenges in drug delivery issues must enlist more realistic, back-to-basics approaches to address fundamental materials properties in complex biological systems, preclinical test beds, and analytical methods to more reliably determine fundamental pharmaceutical figures of merit, including drug carrier purity and batch-batch variability, agent biodistribution, therapeutic index (safety), and efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Drug design and discovery: translational biomedical science varies among countries.

    Science.gov (United States)

    Weaver, Ian N; Weaver, Donald F

    2013-10-01

    Drug design and discovery is an innovation process that translates the outcomes of fundamental biomedical research into therapeutics that are ultimately made available to people with medical disorders in many countries throughout the world. To identify which nations succeed, exceed, or fail at the drug design/discovery endeavor--more specifically, which countries, within the context of their national size and wealth, are "pulling their weight" when it comes to developing medications targeting the myriad of diseases that afflict humankind--we compiled and analyzed a comprehensive survey of all new drugs (small molecular entities and biologics) approved annually throughout the world over the 20-year period from 1991 to 2010. Based upon this analysis, we have devised prediction algorithms to ascertain which countries are successful (or not) in contributing to the worldwide need for effective new therapeutics. © 2013 Wiley Periodicals, Inc.

  19. Designing Ubiquitous Computing to Enhance Children's Learning in Museums

    Science.gov (United States)

    Hall, T.; Bannon, L.

    2006-01-01

    In recent years, novel paradigms of computing have emerged, which enable computational power to be embedded in artefacts and in environments in novel ways. These developments may create new possibilities for using computing to enhance learning. This paper presents the results of a design process that set out to explore interactive techniques,…

  20. Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

    Science.gov (United States)

    Prausnitz, Mark R.; Bommarius, Andreas S.

    2011-01-01

    We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

  1. A Prospective Method to Guide Small Molecule Drug Design

    Science.gov (United States)

    Johnson, Alan T.

    2015-01-01

    At present, small molecule drug design follows a retrospective path when considering what analogs are to be made around a current hit or lead molecule with the focus often on identifying a compound with higher intrinsic potency. What this approach overlooks is the simultaneous need to also improve the physicochemical (PC) and pharmacokinetic (PK)…

  2. Design of new polymeric formulations for drug nanocarriers

    Science.gov (United States)

    Mattu, C.; Li, R.; Sartori, S.; Boffito, M.; Ramtoola, Z.; Ciardelli, G.

    2012-07-01

    In this work, novel strategies for the design and characterization of complex nanosized drug delivery systems for the release of different formulations were proposed and investigated. Natural or synthetic polymers, such as chitosan, poly (D,L lactide) (PLA) and proprietary polyesterurethanes, were used to prepare carriers for different applications in nanomedicine.

  3. Experimental and computational prediction of glass transition temperature of drugs.

    Science.gov (United States)

    Alzghoul, Ahmad; Alhalaweh, Amjad; Mahlin, Denny; Bergström, Christel A S

    2014-12-22

    Glass transition temperature (Tg) is an important inherent property of an amorphous solid material which is usually determined experimentally. In this study, the relation between Tg and melting temperature (Tm) was evaluated using a data set of 71 structurally diverse druglike compounds. Further, in silico models for prediction of Tg were developed based on calculated molecular descriptors and linear (multilinear regression, partial least-squares, principal component regression) and nonlinear (neural network, support vector regression) modeling techniques. The models based on Tm predicted Tg with an RMSE of 19.5 K for the test set. Among the five computational models developed herein the support vector regression gave the best result with RMSE of 18.7 K for the test set using only four chemical descriptors. Hence, two different models that predict Tg of drug-like molecules with high accuracy were developed. If Tm is available, a simple linear regression can be used to predict Tg. However, the results also suggest that support vector regression and calculated molecular descriptors can predict Tg with equal accuracy, already before compound synthesis.

  4. Computational design gains momentum in enzyme catalysis engineering

    NARCIS (Netherlands)

    Wijma, Hein J.; Janssen, Dick B.

    Computational protein design is becoming a powerful tool for tailoring enzymes for specific biotechnological applications. When applied to existing enzymes, computational re-design makes it possible to obtain orders of magnitude improvement in catalytic activity towards a new target substrate.

  5. Design Anthropology, Emerging Technologies and Alternative Computational Futures

    DEFF Research Database (Denmark)

    Smith, Rachel Charlotte

    Emerging technologies are providing a new field for design anthropological inquiry that unite experiences, imaginaries and materialities in complex way and demands new approaches to developing sustainable computational futures.......Emerging technologies are providing a new field for design anthropological inquiry that unite experiences, imaginaries and materialities in complex way and demands new approaches to developing sustainable computational futures....

  6. Children as Educational Computer Game Designers: An Exploratory Study

    Science.gov (United States)

    Baytak, Ahmet; Land, Susan M.; Smith, Brian K.

    2011-01-01

    This study investigated how children designed computer games as artifacts that reflected their understanding of nutrition. Ten 5th grade students were asked to design computer games with the software "Game Maker" for the purpose of teaching 1st graders about nutrition. The results from the case study show that students were able to…

  7. Designing User-Computer Dialogues: Basic Principles and Guidelines.

    Science.gov (United States)

    Harrell, Thomas H.

    This discussion of the design of computerized psychological assessment or testing instruments stresses the importance of the well-designed computer-user interface. The principles underlying the three main functional elements of computer-user dialogue--data entry, data display, and sequential control--are discussed, and basic guidelines derived…

  8. Software For Computer-Aided Design Of Control Systems

    Science.gov (United States)

    Wette, Matthew

    1994-01-01

    Computer Aided Engineering System (CAESY) software developed to provide means to evaluate methods for dealing with users' needs in computer-aided design of control systems. Interpreter program for performing engineering calculations. Incorporates features of both Ada and MATLAB. Designed to be flexible and powerful. Includes internally defined functions, procedures and provides for definition of functions and procedures by user. Written in C language.

  9. Critiquing the Computer-Aided Design of Dental Prostheses.

    Science.gov (United States)

    Fitzpatrick, F. J.; And Others

    This paper describes RaPiD, a computer-aided assistant for the design of dental prostheses called removable partial dentures. The user manipulates icons directly to indicate the desired design solution to a given clinical situation. A developing design is represented as a logic database of components in a design; expert rules are applied as…

  10. How to design some computer WAN

    International Nuclear Information System (INIS)

    Zhang Chengjun; Huang Hongmei

    2001-01-01

    The author introduces a way of how to construct computer WAN, depending on the present condition of enterprise, under the social surrounding in which the technology of internet is rapidly spread and developed at present, and gives a detailed dispose of main network equipment

  11. How to design some computer WAN

    International Nuclear Information System (INIS)

    Zhang Chengjun; Huang Hongmei

    2000-01-01

    The authors introduce a way of how to construct computer WAN, depending on the present condition of enterprise, under the social surrounding in which the technology of internet is rapidly spread and developed at present. And gives the detailed dispose of main network equipment

  12. The Semiempirical Quantum Mechanical Scoring Function for In Silico Drug Design

    Czech Academy of Sciences Publication Activity Database

    Lepšík, Martin; Řezáč, Jan; Kolář, Michal; Pecina, Adam; Hobza, Pavel; Fanfrlík, Jindřich

    2013-01-01

    Roč. 78, č. 9 (2013), s. 921-931 ISSN 2192-6506 R&D Projects: GA ČR GBP208/12/G016 Grant - others:Operational Program Research and Development for Innovations(XE) CZ 1.05/2.1.00/03/0058 Institutional support: RVO:61388963 Keywords : computational chemistry * drug design * noncovalent interactions * quantum chemistry * semiempirical calculations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.242, year: 2013

  13. Universal Design: Implications for Computing Education

    Science.gov (United States)

    Burgstahler, Sheryl

    2011-01-01

    Universal design (UD), a concept that grew from the field of architecture, has recently emerged as a paradigm for designing instructional methods, curriculum, and assessments that are welcoming and accessible to students with a wide range of characteristics, including those related to race, ethnicity, native language, gender, age, and disability.…

  14. [Effects of the new comprehensive system for designating illegal drug components on the abuse of designer drugs and future problems based on an online questionnaire].

    Science.gov (United States)

    Morino, Taichi; Okazaki, Mitsuhiro; Toda, Takaki; Yokoyama, Takashi

    2015-12-01

    Recently, the abuse of designer drugs has become a social problem. Designer drugs are created by modifying part of the chemical structure of drugs that have already been categorized as illegal, thereby creating a different chemical compound in order to evade Pharmaceutical Affairs Law regulations. The new comprehensive system for designating illegal drug components has been in effect since March 2013, and many designer drugs can now be regulated. We conducted an online questionnaire survey of people with a history of designer drug use to elucidate the effects of the new system on the abuse of designer drugs and to identify potential future problems. Over half the subjects obtained designer drugs only before the new system was implemented. Awareness of the system was significantly lower among subjects who obtained designer drugs for the first time after its introduction than those who obtained the drugs only before its implementation. Due to the new system, all methods of acquiring designer drugs saw decreases in activity. However, the ratio of the acquisition of designer drugs via the Internet increased. Since over 50% of the subjects never obtained designer drugs after the new system was introduced, goals that aimed to make drug procurement more difficult were achieved. However, awareness of the new system among subjects who obtained designer drugs after the new system was introduced was significantly low. Therefore, fostering greater public awareness of the new system is necessary. The results of the questionnaire also suggested that acquiring designer drugs through the Internet has hardly been affected by the new system. We strongly hope that there will be a greater push to restrict the sale of designer drugs on the Internet in the near future.

  15. On Architectural Acoustics Design using Computer Simulation

    DEFF Research Database (Denmark)

    Schmidt, Anne Marie Due; Kirkegaard, Poul Henning

    2004-01-01

    The acoustical quality of a given building, or space within the building, is highly dependent on the architectural design. Architectural acoustics design has in the past been based on simple design rules. However, with a growing complexity in the architectural acoustic and the emergence of potent...... room acoustic simulation programs it is now possible to subjectively analyze and evaluate acoustic properties prior to the actual construction of a facility. With the right tools applied, the acoustic design can become an integrated part of the architectural design process. The aim of the present paper...... this information is discussed. The conclusion of the paper is that the application of acoustical simulation programs is most beneficial in the last of three phases but that an application of the program to the two first phases would be preferable and possible with an improvement of the interface of the program....

  16. Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations.

    Science.gov (United States)

    Singh, Pankaj Kumar; Negi, Arvind; Gupta, Pawan Kumar; Chauhan, Monika; Kumar, Raj

    2016-08-01

    Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.

  17. Evaluation of mini super computers for nuclear design applications

    International Nuclear Information System (INIS)

    Altomare, S.; Baradari, F.

    1987-01-01

    The evolution of the mini super computers will force changes from the current environment of performing nuclear design calculations on mainframe computers (such as a CRAY) to mini super computers. This change will come about for a number of reasons. First, the mini super computers currently available in the marketplace offer the power and speed comparable to mainframes and can provide the capability to support highly computer intensive calculations. Second, the equipment is physically smaller and can easily be installed and operated without extensive investments in facilities and operations support. Third, the computer capacity can be acquired with as much needed memory, disk, and tape capacity as may be needed. Another reasons is that the performance/cost ratio has increased drastically as hardware costs have decreased. A study was conducted at the Westinghouse Commercial Nuclear Fuel Division (CNFD) to evaluate the mini super computers for use in nuclear core design. As a result of this evaluation, Westinghouse CNFD is offering a combined hardware/software technology transfer package for core design. This package provides the utility designer with a totally dedicated mini super computer comparable in speed to the CRAY 1S with sufficient capacity for a sizable design group to perform the engineering activities related to nuclear core design and operations support. This also assures the utility of being totally compatible with the CNFD design codes, thus assuring total update compatibility

  18. Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?

    Science.gov (United States)

    Seely, Kathryn A; Prather, Paul L; James, Laura P; Moran, Jeffery H

    2011-02-01

    The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.

  19. Computer-aided dispatching system design specification

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, M.G.

    1997-12-16

    This document defines the performance requirements for a graphic display dispatching system to support Hanford Patrol Operations Center. This document reflects the as-built requirements for the system that was delivered by GTE Northwest, Inc. This system provided a commercial off-the-shelf computer-aided dispatching system and alarm monitoring system currently in operations at the Hanford Patrol Operations Center, Building 2721E. This system also provides alarm back-up capability for the Plutonium Finishing Plant (PFP).

  20. A Design Methodology for Computer Security Testing

    OpenAIRE

    Ramilli, Marco

    2013-01-01

    The field of "computer security" is often considered something in between Art and Science. This is partly due to the lack of widely agreed and standardized methodologies to evaluate the degree of the security of a system. This dissertation intends to contribute to this area by investigating the most common security testing strategies applied nowadays and by proposing an enhanced methodology that may be effectively applied to different threat scenarios with the same degree of effectiveness. ...

  1. Computer-Aided dispatching system design specification

    International Nuclear Information System (INIS)

    Briggs, M.G.

    1996-01-01

    This document defines the performance requirements for a graphic display dispatching system to support Hanford Patrol emergency response. This system is defined as a Commercial-Off the-Shelf computer dispatching system providing both text and graphical display information while interfacing with the diverse reporting system within the Hanford Facility. This system also provided expansion capabilities to integrate Hanford Fire and the Occurrence Notification Center and provides back-up capabilities for the Plutonium Processing Facility

  2. Computer-aided dispatching system design specification

    International Nuclear Information System (INIS)

    Briggs, M.G.

    1997-01-01

    This document defines the performance requirements for a graphic display dispatching system to support Hanford Patrol Operations Center. This document reflects the as-built requirements for the system that was delivered by GTE Northwest, Inc. This system provided a commercial off-the-shelf computer-aided dispatching system and alarm monitoring system currently in operations at the Hanford Patrol Operations Center, Building 2721E. This system also provides alarm back-up capability for the Plutonium Finishing Plant (PFP)

  3. On architectural acoustic design using computer simulation

    DEFF Research Database (Denmark)

    Schmidt, Anne Marie Due; Kirkegaard, Poul Henning

    2004-01-01

    properties prior to the actual construction of a building. With the right tools applied, acoustic design can become an integral part of the architectural design process. The aim of this paper is to investigate the field of application that an acoustic simulation programme can have during an architectural...... acoustic design process. The emphasis is put on the first three out of five phases in the working process of the architect and a case study is carried out in which each phase is represented by typical results ? as exemplified with reference to the design of Bagsværd Church by Jørn Utzon. The paper...... discusses the advantages and disadvantages of the programme in each phase compared to the works of architects not using acoustic simulation programmes. The conclusion of the paper is that the application of acoustic simulation programs is most beneficial in the last of three phases but an application...

  4. Computational chemical product design problems under property uncertainties

    DEFF Research Database (Denmark)

    Frutiger, Jerome; Cignitti, Stefano; Abildskov, Jens

    2017-01-01

    Three different strategies of how to combine computational chemical product design with Monte Carlo based methods for uncertainty analysis of chemical properties are outlined. One method consists of a computer-aided molecular design (CAMD) solution and a post-processing property uncertainty...... fluid design. While the higher end of the uncertainty range of the process model output is similar for the best performing fluids, the lower end of the uncertainty range differs largely....

  5. 76 FR 44613 - Designation of Eight Counties as High Intensity Drug Trafficking Areas

    Science.gov (United States)

    2011-07-26

    ... OFFICE OF NATIONAL DRUG CONTROL POLICY Designation of Eight Counties as High Intensity Drug Trafficking Areas AGENCY: Office of National Drug Control Policy. ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy has designated eight additional counties as High Intensity Drug...

  6. Computational Design of Advanced Nuclear Fuels

    International Nuclear Information System (INIS)

    Savrasov, Sergey; Kotliar, Gabriel; Haule, Kristjan

    2014-01-01

    The objective of the project was to develop a method for theoretical understanding of nuclear fuel materials whose physical and thermophysical properties can be predicted from first principles using a novel dynamical mean field method for electronic structure calculations. We concentrated our study on uranium, plutonium, their oxides, nitrides, carbides, as well as some rare earth materials whose 4f eletrons provide a simplified framework for understanding complex behavior of the f electrons. We addressed the issues connected to the electronic structure, lattice instabilities, phonon and magnon dynamics as well as thermal conductivity. This allowed us to evaluate characteristics of advanced nuclear fuel systems using computer based simulations and avoid costly experiments.

  7. Computer-Aided dispatching system design specification

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, M.G.

    1996-09-27

    This document defines the performance requirements for a graphic display dispatching system to support Hanford Patrol emergency response. This document outlines the negotiated requirements as agreed to by GTE Northwest during technical contract discussions. This system defines a commercial off-the-shelf computer dispatching system providing both test and graphic display information while interfacing with diverse alarm reporting system within the Hanford Site. This system provided expansion capability to integrate Hanford Fire and the Occurrence Notification Center. The system also provided back-up capability for the Plutonium Processing Facility (PFP).

  8. Benchmarking therapeutic drug monitoring software: a review of available computer tools.

    Science.gov (United States)

    Fuchs, Aline; Csajka, Chantal; Thoma, Yann; Buclin, Thierry; Widmer, Nicolas

    2013-01-01

    Therapeutic drug monitoring (TDM) aims to optimize treatments by individualizing dosage regimens based on the measurement of blood concentrations. Dosage individualization to maintain concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculations currently represent the gold standard TDM approach but require computation assistance. In recent decades computer programs have been developed to assist clinicians in this assignment. The aim of this survey was to assess and compare computer tools designed to support TDM clinical activities. The literature and the Internet were searched to identify software. All programs were tested on personal computers. Each program was scored against a standardized grid covering pharmacokinetic relevance, user friendliness, computing aspects, interfacing and storage. A weighting factor was applied to each criterion of the grid to account for its relative importance. To assess the robustness of the software, six representative clinical vignettes were processed through each of them. Altogether, 12 software tools were identified, tested and ranked, representing a comprehensive review of the available software. Numbers of drugs handled by the software vary widely (from two to 180), and eight programs offer users the possibility of adding new drug models based on population pharmacokinetic analyses. Bayesian computation to predict dosage adaptation from blood concentration (a posteriori adjustment) is performed by ten tools, while nine are also able to propose a priori dosage regimens, based only on individual patient covariates such as age, sex and bodyweight. Among those applying Bayesian calculation, MM-USC*PACK© uses the non-parametric approach. The top two programs emerging from this benchmark were MwPharm© and TCIWorks. Most other programs evaluated had good potential while being less sophisticated or less user friendly. Programs vary in complexity and might not fit all healthcare

  9. General aviation design synthesis utilizing interactive computer graphics

    Science.gov (United States)

    Galloway, T. L.; Smith, M. R.

    1976-01-01

    Interactive computer graphics is a fast growing area of computer application, due to such factors as substantial cost reductions in hardware, general availability of software, and expanded data communication networks. In addition to allowing faster and more meaningful input/output, computer graphics permits the use of data in graphic form to carry out parametric studies for configuration selection and for assessing the impact of advanced technologies on general aviation designs. The incorporation of interactive computer graphics into a NASA developed general aviation synthesis program is described, and the potential uses of the synthesis program in preliminary design are demonstrated.

  10. Computational manufacturing as a bridge between design and production.

    Science.gov (United States)

    Tikhonravov, Alexander V; Trubetskov, Michael K

    2005-11-10

    Computational manufacturing of optical coatings is a research area that can be placed between theoretical designing and practical manufacturing in the same way that computational physics can be placed between theoretical and experimental physics. Investigations in this area have been performed for more than 30 years under the name of computer simulation of manufacturing and monitoring processes. Our goal is to attract attention to the increasing importance of computational manufacturing at the current state of the art in the design and manufacture of optical coatings and to demonstrate possible applications of this research tool.

  11. Computer Assisted Instructional Design for Computer-Based Instruction. Final Report. Working Papers.

    Science.gov (United States)

    Russell, Daniel M.; Pirolli, Peter

    Recent advances in artificial intelligence and the cognitive sciences have made it possible to develop successful intelligent computer-aided instructional systems for technical and scientific training. In addition, computer-aided design (CAD) environments that support the rapid development of such computer-based instruction have also been recently…

  12. Computer Graphics 2: More of the Best Computer Art and Design.

    Science.gov (United States)

    1994

    This collection of computer generated images aims to present media tools and processes, stimulate ideas, and inspire artists and art students working in computer-related design. The images are representative of state-of-the-art editorial, broadcast, packaging, fine arts, and graphic techniques possible through computer generation. Each image is…

  13. Associating Drugs, Targets and Clinical Outcomes into an Integrated Network Affords a New Platform for Computer-Aided Drug Repurposing

    DEFF Research Database (Denmark)

    Oprea, Tudor; Nielsen, Sonny Kim; Ursu, Oleg

    2011-01-01

    benefit from an integrated, semantic-web compliant computer-aided drug repurposing (CADR) effort, one that would enable deep data mining of associations between approved drugs (D), targets (T), clinical outcomes (CO) and SE. We report preliminary results from text mining and multivariate statistics, based...... on 7684 approved drug labels, ADL (Dailymed) via text mining. From the ADL corresponding to 988 unique drugs, the "adverse reactions" section was mapped onto 174 SE, then clustered via principal component analysis into a 5 x 5 self-organizing map that was integrated into a Cytoscape network of SE......Finding new uses for old drugs is a strategy embraced by the pharmaceutical industry, with increasing participation from the academic sector. Drug repurposing efforts focus on identifying novel modes of action, but not in a systematic manner. With intensive data mining and curation, we aim to apply...

  14. A Computational Lens on Design Research

    Science.gov (United States)

    Hoyles, Celia; Noss, Richard

    2015-01-01

    In this commentary, we briefly review the collective effort of design researchers to weave theory with empirical results, in order to gain a better understanding of the processes of learning. We seek to respond to this challenging agenda by centring on the evolution of one sub-field: namely that which involves investigations within a…

  15. Computation, architectural design and fabrication logic

    DEFF Research Database (Denmark)

    Larsen, Niels Martin

    2016-01-01

    Digital fabrication and digital form generation can change the way different professions interact in relation to the development and construction of architecture. The technologies can provide a more integrated design process and expand the architectural vocabulary. At Aarhus School of Architectur...

  16. Psychiatric aspects of designer drugs and new psychoactive substances consumption

    Directory of Open Access Journals (Sweden)

    Antsyborov A.V.

    2017-02-01

    Full Text Available according to the authors, appeared not long ago new psychoactive substances (designer drugs, including synthetic cannabinoids, derivatives of cathinone, phenethylamines, new stimulants, synthetic opioids, tryptamine derivatives, phencyclidine, piperazine, agonists of GABA (A/B receptors have become a serious problem for both consumers and doctors. Consumers of these substances are attracted primarily by the intensity of psychoactive effects, as well as «legal purity», which is declared by shadow producers. This indicates that there are some significant difficulties of laboratory typing of new surfactants. Designer drugs when ingested, can affect a range of neurotransmitter pathways/receptors: dopamine, cannabinoid (CB1, GABA(A/B, 5-HT2A, glutamate, and k-opioid receptors (KOR, the imbalance of which leads to the development of polymorphic psychotic disorders.

  17. Basic design of parallel computational program for probabilistic structural analysis

    International Nuclear Information System (INIS)

    Kaji, Yoshiyuki; Arai, Taketoshi; Gu, Wenwei; Nakamura, Hitoshi

    1999-06-01

    In our laboratory, for 'development of damage evaluation method of structural brittle materials by microscopic fracture mechanics and probabilistic theory' (nuclear computational science cross-over research) we examine computational method related to super parallel computation system which is coupled with material strength theory based on microscopic fracture mechanics for latent cracks and continuum structural model to develop new structural reliability evaluation methods for ceramic structures. This technical report is the review results regarding probabilistic structural mechanics theory, basic terms of formula and program methods of parallel computation which are related to principal terms in basic design of computational mechanics program. (author)

  18. Basic design of parallel computational program for probabilistic structural analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kaji, Yoshiyuki; Arai, Taketoshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Gu, Wenwei; Nakamura, Hitoshi

    1999-06-01

    In our laboratory, for `development of damage evaluation method of structural brittle materials by microscopic fracture mechanics and probabilistic theory` (nuclear computational science cross-over research) we examine computational method related to super parallel computation system which is coupled with material strength theory based on microscopic fracture mechanics for latent cracks and continuum structural model to develop new structural reliability evaluation methods for ceramic structures. This technical report is the review results regarding probabilistic structural mechanics theory, basic terms of formula and program methods of parallel computation which are related to principal terms in basic design of computational mechanics program. (author)

  19. Computer organization and design the hardware/software interface

    CERN Document Server

    Hennessy, John L

    1994-01-01

    Computer Organization and Design: The Hardware/Software Interface presents the interaction between hardware and software at a variety of levels, which offers a framework for understanding the fundamentals of computing. This book focuses on the concepts that are the basis for computers.Organized into nine chapters, this book begins with an overview of the computer revolution. This text then explains the concepts and algorithms used in modern computer arithmetic. Other chapters consider the abstractions and concepts in memory hierarchies by starting with the simplest possible cache. This book di

  20. Integrating Cloud-Computing-Specific Model into Aircraft Design

    Science.gov (United States)

    Zhimin, Tian; Qi, Lin; Guangwen, Yang

    Cloud Computing is becoming increasingly relevant, as it will enable companies involved in spreading this technology to open the door to Web 3.0. In the paper, the new categories of services introduced will slowly replace many types of computational resources currently used. In this perspective, grid computing, the basic element for the large scale supply of cloud services, will play a fundamental role in defining how those services will be provided. The paper tries to integrate cloud computing specific model into aircraft design. This work has acquired good results in sharing licenses of large scale and expensive software, such as CFD (Computational Fluid Dynamics), UG, CATIA, and so on.

  1. Metamodels for Computer-Based Engineering Design: Survey and Recommendations

    Science.gov (United States)

    Simpson, Timothy W.; Peplinski, Jesse; Koch, Patrick N.; Allen, Janet K.

    1997-01-01

    The use of statistical techniques to build approximations of expensive computer analysis codes pervades much of todays engineering design. These statistical approximations, or metamodels, are used to replace the actual expensive computer analyses, facilitating multidisciplinary, multiobjective optimization and concept exploration. In this paper we review several of these techniques including design of experiments, response surface methodology, Taguchi methods, neural networks, inductive learning, and kriging. We survey their existing application in engineering design and then address the dangers of applying traditional statistical techniques to approximate deterministic computer analysis codes. We conclude with recommendations for the appropriate use of statistical approximation techniques in given situations and how common pitfalls can be avoided.

  2. Program computes single-point failures in critical system designs

    Science.gov (United States)

    Brown, W. R.

    1967-01-01

    Computer program analyzes the designs of critical systems that will either prove the design is free of single-point failures or detect each member of the population of single-point failures inherent in a system design. This program should find application in the checkout of redundant circuits and digital systems.

  3. New computing systems, future computing environment, and their implications on structural analysis and design

    Science.gov (United States)

    Noor, Ahmed K.; Housner, Jerrold M.

    1993-01-01

    Recent advances in computer technology that are likely to impact structural analysis and design of flight vehicles are reviewed. A brief summary is given of the advances in microelectronics, networking technologies, and in the user-interface hardware and software. The major features of new and projected computing systems, including high performance computers, parallel processing machines, and small systems, are described. Advances in programming environments, numerical algorithms, and computational strategies for new computing systems are reviewed. The impact of the advances in computer technology on structural analysis and the design of flight vehicles is described. A scenario for future computing paradigms is presented, and the near-term needs in the computational structures area are outlined.

  4. Computer models in the design of FXR

    International Nuclear Information System (INIS)

    Vogtlin, G.; Kuenning, R.

    1980-01-01

    Lawrence Livermore National Laboratory is developing a 15 to 20 MeV electron accelerator with a beam current goal of 4 kA. This accelerator will be used for flash radiography and has a requirement of high reliability. Components being developed include spark gaps, Marx generators, water Blumleins and oil insulation systems. A SCEPTRE model was developed that takes into consideration the non-linearity of the ferrite and the time dependency of the emission from a field emitter cathode. This model was used to predict an optimum charge time to obtain maximum magnetic flux change from the ferrite. This model and its application will be discussed. JASON was used extensively to determine optimum locations and shapes of supports and insulators. It was also used to determine stress within bubbles adjacent to walls in oil. Computer results will be shown and bubble breakdown will be related to bubble size

  5. 21 CFR 516.29 - Termination of MUMS-drug designation.

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.29 Termination of MUMS-drug designation. (a... exclusive marketing rights under this subpart. (d) FDA may terminate designation if it independently...

  6. Computational Chemistry Toolkit for Energetic Materials Design

    Science.gov (United States)

    2006-11-01

    industry are aggressively engaged in efforts to develop multiscale modeling and simulation methodologies to model and analyze complex phenomena across...energetic materials design. It is hoped that this toolkit will evolve into a collection of well-integrated multiscale modeling methodologies...Experimenta Theoreticala This Work 1-5-Diamino-4- methyl- tetrazolium nitrate 8.4 41.7 47.5 1-5-Diamino-4- methyl- tetrazolium azide 138.1 161.6

  7. Towards practical control design using neural computation

    Science.gov (United States)

    Troudet, Terry; Garg, Sanjay; Mattern, Duane; Merrill, Walter

    1991-01-01

    The objective is to develop neural network based control design techniques which address the issue of performance/control effort tradeoff. Additionally, the control design needs to address the important issue if achieving adequate performance in the presence of actuator nonlinearities such as position and rate limits. These issues are discussed using the example of aircraft flight control. Given a set of pilot input commands, a feedforward net is trained to control the vehicle within the constraints imposed by the actuators. This is achieved by minimizing an objective function which is the sum of the tracking errors, control input rates and control input deflections. A tradeoff between tracking performance and control smoothness is obtained by varying, adaptively, the weights of the objective function. The neurocontroller performance is evaluated in the presence of actuator dynamics using a simulation of the vehicle. Appropriate selection of the different weights in the objective function resulted in the good tracking of the pilot commands and smooth neurocontrol. An extension of the neurocontroller design approach is proposed to enhance its practicality.

  8. Design of diversity and focused combinatorial libraries in drug discovery.

    Science.gov (United States)

    Young, S Stanley; Ge, Nanxiang

    2004-05-01

    Using well-characterized chemical reactions and readily available monomers, chemists are able to create sets of compounds, termed libraries, which are useful in drug discovery processes. The design of combinatorial chemical libraries can be complex and there has been much information recently published offering suggestions on how the design process can be carried out. This review focuses on literature with the goal of organizing current thinking. At this point in time, it is clear that benchmarking of current suggested methods is required as opposed to further new methods.

  9. Computational design of proteins with novel structure and functions

    International Nuclear Information System (INIS)

    Yang Wei; Lai Lu-Hua

    2016-01-01

    Computational design of proteins is a relatively new field, where scientists search the enormous sequence space for sequences that can fold into desired structure and perform desired functions. With the computational approach, proteins can be designed, for example, as regulators of biological processes, novel enzymes, or as biotherapeutics. These approaches not only provide valuable information for understanding of sequence–structure–function relations in proteins, but also hold promise for applications to protein engineering and biomedical research. In this review, we briefly introduce the rationale for computational protein design, then summarize the recent progress in this field, including de novo protein design, enzyme design, and design of protein–protein interactions. Challenges and future prospects of this field are also discussed. (topical review)

  10. ASDA - Advanced Suit Design Analyzer computer program

    Science.gov (United States)

    Bue, Grant C.; Conger, Bruce C.; Iovine, John V.; Chang, Chi-Min

    1992-01-01

    An ASDA model developed to evaluate the heat and mass transfer characteristics of advanced pressurized suit design concepts for low pressure or vacuum planetary applications is presented. The model is based on a generalized 3-layer suit that uses the Systems Integrated Numerical Differencing Analyzer '85 in conjunction with a 41-node FORTRAN routine. The latter simulates the transient heat transfer and respiratory processes of a human body in a suited environment. The user options for the suit encompass a liquid cooled garment, a removable jacket, a CO2/H2O permeable layer, and a phase change layer.

  11. 77 FR 39498 - Guidances for Industry and Food and Drug Administration Staff: Computer-Assisted Detection...

    Science.gov (United States)

    2012-07-03

    ...] Guidances for Industry and Food and Drug Administration Staff: Computer-Assisted Detection Devices Applied... Clinical Performance Assessment: Considerations for Computer-Assisted Detection Devices Applied to... guidance, entitled ``Computer-Assisted Detection Devices Applied to Radiology Images and Radiology Device...

  12. Anti-tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: From drug product design to in vivo testing

    DEFF Research Database (Denmark)

    Genina, Natalja; Boetker, Johan Peter; Colombo, Stefano

    2017-01-01

    for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion...... (HME) of the drug-containing filaments. The structure of the fabricated dcDUs was visualized by scanning electron microscopy (SEM). The 3D printed compartmentalized shells were loaded with filaments containing active pharmaceutical ingredient (API) and selectively sealed to modulate drug dissolution...

  13. Computational materials design for energy applications

    Science.gov (United States)

    Ozolins, Vidvuds

    2013-03-01

    General adoption of sustainable energy technologies depends on the discovery and development of new high-performance materials. For instance, waste heat recovery and electricity generation via the solar thermal route require bulk thermoelectrics with a high figure of merit (ZT) and thermal stability at high-temperatures. Energy recovery applications (e.g., regenerative braking) call for the development of rapidly chargeable systems for electrical energy storage, such as electrochemical supercapacitors. Similarly, use of hydrogen as vehicular fuel depends on the ability to store hydrogen at high volumetric and gravimetric densities, as well as on the ability to extract it at ambient temperatures at sufficiently rapid rates. We will discuss how first-principles computational methods based on quantum mechanics and statistical physics can drive the understanding, improvement and prediction of new energy materials. We will cover prediction and experimental verification of new earth-abundant thermoelectrics, transition metal oxides for electrochemical supercapacitors, and kinetics of mass transport in complex metal hydrides. Research has been supported by the US Department of Energy under grant Nos. DE-SC0001342, DE-SC0001054, DE-FG02-07ER46433, and DE-FC36-08GO18136.

  14. Computer aided system for parametric design of combination die

    Science.gov (United States)

    Naranje, Vishal G.; Hussein, H. M. A.; Kumar, S.

    2017-09-01

    In this paper, a computer aided system for parametric design of combination dies is presented. The system is developed using knowledge based system technique of artificial intelligence. The system is capable to design combination dies for production of sheet metal parts having punching and cupping operations. The system is coded in Visual Basic and interfaced with AutoCAD software. The low cost of the proposed system will help die designers of small and medium scale sheet metal industries for design of combination dies for similar type of products. The proposed system is capable to reduce design time and efforts of die designers for design of combination dies.

  15. Computer Aided Design Tools for Extreme Environment Electronics, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This project aims to provide Computer Aided Design (CAD) tools for radiation-tolerant, wide-temperature-range digital, analog, mixed-signal, and radio-frequency...

  16. Computer graphics application in the engineering design integration system

    Science.gov (United States)

    Glatt, C. R.; Abel, R. W.; Hirsch, G. N.; Alford, G. E.; Colquitt, W. N.; Stewart, W. A.

    1975-01-01

    The computer graphics aspect of the Engineering Design Integration (EDIN) system and its application to design problems were discussed. Three basic types of computer graphics may be used with the EDIN system for the evaluation of aerospace vehicles preliminary designs: offline graphics systems using vellum-inking or photographic processes, online graphics systems characterized by direct coupled low cost storage tube terminals with limited interactive capabilities, and a minicomputer based refresh terminal offering highly interactive capabilities. The offline line systems are characterized by high quality (resolution better than 0.254 mm) and slow turnaround (one to four days). The online systems are characterized by low cost, instant visualization of the computer results, slow line speed (300 BAUD), poor hard copy, and the early limitations on vector graphic input capabilities. The recent acquisition of the Adage 330 Graphic Display system has greatly enhanced the potential for interactive computer aided design.

  17. Integration of case study approach, project design and computer ...

    African Journals Online (AJOL)

    Integration of case study approach, project design and computer modeling in managerial accounting education ... Journal of Fundamental and Applied Sciences ... in the Laboratory of Management Accounting and Controlling Systems at the ...

  18. Design of shared unit-dose drug distribution network using multi-level particle swarm optimization.

    Science.gov (United States)

    Chen, Linjie; Monteiro, Thibaud; Wang, Tao; Marcon, Eric

    2018-03-01

    Unit-dose drug distribution systems provide optimal choices in terms of medication security and efficiency for organizing the drug-use process in large hospitals. As small hospitals have to share such automatic systems for economic reasons, the structure of their logistic organization becomes a very sensitive issue. In the research reported here, we develop a generalized multi-level optimization method - multi-level particle swarm optimization (MLPSO) - to design a shared unit-dose drug distribution network. Structurally, the problem studied can be considered as a type of capacitated location-routing problem (CLRP) with new constraints related to specific production planning. This kind of problem implies that a multi-level optimization should be performed in order to minimize logistic operating costs. Our results show that with the proposed algorithm, a more suitable modeling framework, as well as computational time savings and better optimization performance are obtained than that reported in the literature on this subject.

  19. Design and applications of Computed Industrial Tomographic Imaging System (CITIS)

    Energy Technology Data Exchange (ETDEWEB)

    Ramakrishna, G S; Kumar, Umesh; Datta, S S [Bhabha Atomic Research Centre, Bombay (India). Isotope Div.

    1994-12-31

    This paper highlights the design and development of a prototype Computed Tomographic (CT) imaging system and its software for image reconstruction, simulation and display. It also describes results obtained with several test specimens including Dhruva reactor uranium fuel assembly and possibility of using neutrons as well as high energy x-rays in computed tomography. 5 refs., 4 figs.

  20. Cloud Computing for Teaching Practice: A New Design?

    Science.gov (United States)

    Saadatdoost, Robab; Sim, Alex Tze Hiang; Jafarkarimi, Hosein; Hee, Jee Mei; Saadatdoost, Leila

    2014-01-01

    Recently researchers have shown an increased interest in cloud computing technology. It is becoming increasingly difficult to ignore cloud computing technology in education context. However rapid changes in information technology are having a serious effect on teaching framework designs. So far, however, there has been little discussion about…

  1. Automatic design of optical systems by digital computer

    Science.gov (United States)

    Casad, T. A.; Schmidt, L. F.

    1967-01-01

    Computer program uses geometrical optical techniques and a least squares optimization method employing computing equipment for the automatic design of optical systems. It evaluates changes in various optical parameters, provides comprehensive ray-tracing, and generally determines the acceptability of the optical system characteristics.

  2. User Participation and Participatory Design: Topics in Computing Education.

    Science.gov (United States)

    Kautz, Karlheinz

    1996-01-01

    Discusses user participation and participatory design in the context of formal education for computing professionals. Topics include the current curriculum debate; mathematical- and engineering-based education; traditional system-development training; and an example of a course program that includes computers and society, and prototyping. (53…

  3. Computational tools for cyclotron design, commissioning, and operation

    International Nuclear Information System (INIS)

    Kost, C.J.

    1989-05-01

    Many support systems are required in the design, commissioning, and normal operation of a modern cyclotron. Presented is an overview of the computing environment developed during these various stages at TRIUMF. The current computing environment is also discussed, with emphasis on how one can provide an integrated system which is user-friendly

  4. Computer codes used in particle accelerator design: First edition

    International Nuclear Information System (INIS)

    1987-01-01

    This paper contains a listing of more than 150 programs that have been used in the design and analysis of accelerators. Given on each citation are person to contact, classification of the computer code, publications describing the code, computer and language runned on, and a short description of the code. Codes are indexed by subject, person to contact, and code acronym

  5. Integrating computer programs for engineering analysis and design

    Science.gov (United States)

    Wilhite, A. W.; Crisp, V. K.; Johnson, S. C.

    1983-01-01

    The design of a third-generation system for integrating computer programs for engineering and design has been developed for the Aerospace Vehicle Interactive Design (AVID) system. This system consists of an engineering data management system, program interface software, a user interface, and a geometry system. A relational information system (ARIS) was developed specifically for the computer-aided engineering system. It is used for a repository of design data that are communicated between analysis programs, for a dictionary that describes these design data, for a directory that describes the analysis programs, and for other system functions. A method is described for interfacing independent analysis programs into a loosely-coupled design system. This method emphasizes an interactive extension of analysis techniques and manipulation of design data. Also, integrity mechanisms exist to maintain database correctness for multidisciplinary design tasks by an individual or a team of specialists. Finally, a prototype user interface program has been developed to aid in system utilization.

  6. Drug Partitioning in Micellar Media and Its Implications in Rational Drug Design: Insights with Streptomycin.

    Science.gov (United States)

    Judy, Eva; Pagariya, Darshna; Kishore, Nand

    2018-03-20

    Oral bioavailability of a drug molecule requires its effective delivery to the target site. In general, majority of synthetically developed molecular entities have high hydrophobic nature as well as low bioavailability, therefore the need for suitable delivery vehicles arises. Self-assembled structures such as micelles, niosomes, and liposomes have been used as effective delivery vehicles and studied extensively. However, the information available in literature is mostly qualitative in nature. We have quantitatively investigated the partitioning of antibiotic drug streptomycin into cationic, nonionic, and a mixture of cationic and nonionic surfactant micelles and its interaction with the transport protein serum albumin upon subsequent delivery. A combination of calorimetry and spectroscopy has been used to obtain the thermodynamic signatures associated with partitioning and interaction with the protein and the resulting conformational changes in the latter. The results have been correlated with other class of drugs of different nature to understand the role of molecular features in the partitioning process. These studies are oriented toward understanding the physical chemistry of partitioning of a variety of drug molecules into suitable delivery vehicles and hence establishing structure-property-energetics relationships. Such studies provide general guidelines toward a broader goal of rational drug design.

  7. A Perspective on Computational Human Performance Models as Design Tools

    Science.gov (United States)

    Jones, Patricia M.

    2010-01-01

    The design of interactive systems, including levels of automation, displays, and controls, is usually based on design guidelines and iterative empirical prototyping. A complementary approach is to use computational human performance models to evaluate designs. An integrated strategy of model-based and empirical test and evaluation activities is particularly attractive as a methodology for verification and validation of human-rated systems for commercial space. This talk will review several computational human performance modeling approaches and their applicability to design of display and control requirements.

  8. Enzyme (re)design: lessons from natural evolution and computation.

    Science.gov (United States)

    Gerlt, John A; Babbitt, Patricia C

    2009-02-01

    The (re)design of enzymes to catalyze 'new' reactions is a topic of considerable practical and intellectual interest. Directed evolution (random mutagenesis followed by screening/selection) has been used widely to identify novel biocatalysts. However, 'rational' approaches using either natural divergent evolution or computational predictions based on chemical principles have been less successful. This review summarizes recent progress in evolution-based and computation-based (re)design.

  9. Computer organization and design the hardware/software interface

    CERN Document Server

    Patterson, David A

    2013-01-01

    The 5th edition of Computer Organization and Design moves forward into the post-PC era with new examples, exercises, and material highlighting the emergence of mobile computing and the cloud. This generational change is emphasized and explored with updated content featuring tablet computers, cloud infrastructure, and the ARM (mobile computing devices) and x86 (cloud computing) architectures. Because an understanding of modern hardware is essential to achieving good performance and energy efficiency, this edition adds a new concrete example, "Going Faster," used throughout the text to demonstrate extremely effective optimization techniques. Also new to this edition is discussion of the "Eight Great Ideas" of computer architecture. As with previous editions, a MIPS processor is the core used to present the fundamentals of hardware technologies, assembly language, computer arithmetic, pipelining, memory hierarchies and I/O. Optimization techniques featured throughout the text. It covers parallelism in depth with...

  10. Software design for resilient computer systems

    CERN Document Server

    Schagaev, Igor

    2016-01-01

    This book addresses the question of how system software should be designed to account for faults, and which fault tolerance features it should provide for highest reliability. The authors first show how the system software interacts with the hardware to tolerate faults. They analyze and further develop the theory of fault tolerance to understand the different ways to increase the reliability of a system, with special attention on the role of system software in this process. They further develop the general algorithm of fault tolerance (GAFT) with its three main processes: hardware checking, preparation for recovery, and the recovery procedure. For each of the three processes, they analyze the requirements and properties theoretically and give possible implementation scenarios and system software support required. Based on the theoretical results, the authors derive an Oberon-based programming language with direct support of the three processes of GAFT. In the last part of this book, they introduce a simulator...

  11. Medicinal Chemistry Projects Requiring Imaginative Structure-Based Drug Design Methods.

    Science.gov (United States)

    Moitessier, Nicolas; Pottel, Joshua; Therrien, Eric; Englebienne, Pablo; Liu, Zhaomin; Tomberg, Anna; Corbeil, Christopher R

    2016-09-20

    Computational methods for docking small molecules to proteins are prominent in drug discovery. There are hundreds, if not thousands, of documented examples-and several pertinent cases within our research program. Fifteen years ago, our first docking-guided drug design project yielded nanomolar metalloproteinase inhibitors and illustrated the potential of structure-based drug design. Subsequent applications of docking programs to the design of integrin antagonists, BACE-1 inhibitors, and aminoglycosides binding to bacterial RNA demonstrated that available docking programs needed significant improvement. At that time, docking programs primarily considered flexible ligands and rigid proteins. We demonstrated that accounting for protein flexibility, employing displaceable water molecules, and using ligand-based pharmacophores improved the docking accuracy of existing methods-enabling the design of bioactive molecules. The success prompted the development of our own program, Fitted, implementing all of these aspects. The primary motivation has always been to respond to the needs of drug design studies; the majority of the concepts behind the evolution of Fitted are rooted in medicinal chemistry projects and collaborations. Several examples follow: (1) Searching for HDAC inhibitors led us to develop methods considering drug-zinc coordination and its effect on the pKa of surrounding residues. (2) Targeting covalent prolyl oligopeptidase (POP) inhibitors prompted an update to Fitted to identify reactive groups and form bonds with a given residue (e.g., a catalytic residue) when the geometry allows it. Fitted-the first fully automated covalent docking program-was successfully applied to the discovery of four new classes of covalent POP inhibitors. As a result, efficient stereoselective syntheses of a few screening hits were prioritized rather than synthesizing large chemical libraries-yielding nanomolar inhibitors. (3) In order to study the metabolism of POP inhibitors by

  12. Large-scale computational drug repositioning to find treatments for rare diseases.

    Science.gov (United States)

    Govindaraj, Rajiv Gandhi; Naderi, Misagh; Singha, Manali; Lemoine, Jeffrey; Brylinski, Michal

    2018-01-01

    Rare, or orphan, diseases are conditions afflicting a small subset of people in a population. Although these disorders collectively pose significant health care problems, drug companies require government incentives to develop drugs for rare diseases due to extremely limited individual markets. Computer-aided drug repositioning, i.e., finding new indications for existing drugs, is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Structure-based matching of drug-binding pockets is among the most promising computational techniques to inform drug repositioning. In order to find new targets for known drugs ultimately leading to drug repositioning, we recently developed e MatchSite, a new computer program to compare drug-binding sites. In this study, e MatchSite is combined with virtual screening to systematically explore opportunities to reposition known drugs to proteins associated with rare diseases. The effectiveness of this integrated approach is demonstrated for a kinase inhibitor, which is a confirmed candidate for repositioning to synapsin Ia. The resulting dataset comprises 31,142 putative drug-target complexes linked to 980 orphan diseases. The modeling accuracy is evaluated against the structural data recently released for tyrosine-protein kinase HCK. To illustrate how potential therapeutics for rare diseases can be identified, we discuss a possibility to repurpose a steroidal aromatase inhibitor to treat Niemann-Pick disease type C. Overall, the exhaustive exploration of the drug repositioning space exposes new opportunities to combat orphan diseases with existing drugs. DrugBank/Orphanet repositioning data are freely available to research community at https://osf.io/qdjup/.

  13. A network integration approach for drug-target interaction prediction and computational drug repositioning from heterogeneous information.

    Science.gov (United States)

    Luo, Yunan; Zhao, Xinbin; Zhou, Jingtian; Yang, Jinglin; Zhang, Yanqing; Kuang, Wenhua; Peng, Jian; Chen, Ligong; Zeng, Jianyang

    2017-09-18

    The emergence of large-scale genomic, chemical and pharmacological data provides new opportunities for drug discovery and repositioning. In this work, we develop a computational pipeline, called DTINet, to predict novel drug-target interactions from a constructed heterogeneous network, which integrates diverse drug-related information. DTINet focuses on learning a low-dimensional vector representation of features, which accurately explains the topological properties of individual nodes in the heterogeneous network, and then makes prediction based on these representations via a vector space projection scheme. DTINet achieves substantial performance improvement over other state-of-the-art methods for drug-target interaction prediction. Moreover, we experimentally validate the novel interactions between three drugs and the cyclooxygenase proteins predicted by DTINet, and demonstrate the new potential applications of these identified cyclooxygenase inhibitors in preventing inflammatory diseases. These results indicate that DTINet can provide a practically useful tool for integrating heterogeneous information to predict new drug-target interactions and repurpose existing drugs.Network-based data integration for drug-target prediction is a promising avenue for drug repositioning, but performance is wanting. Here, the authors introduce DTINet, whose performance is enhanced in the face of noisy, incomplete and high-dimensional biological data by learning low-dimensional vector representations.

  14. Computational design of in vivo biomarkers

    International Nuclear Information System (INIS)

    Somogyi, Bálint; Gali, Adam

    2014-01-01

    Fluorescent semiconductor nanocrystals (or quantum dots) are very promising agents for bioimaging applications because their optical properties are superior compared to those of conventional organic dyes. However, not all the properties of these quantum dots suit the stringent criteria of in vivo applications, i.e. their employment in living organisms that might be of importance in therapy and medicine. In our review, we first summarize the properties of an ‘ideal’ biomarker needed for in vivo applications. Despite recent efforts, no such hand-made fluorescent quantum dot exists that may be considered as ‘ideal’ in this respect. We propose that ab initio atomistic simulations with predictive power can be used to design ‘ideal’ in vivo fluorescent semiconductor nanoparticles. We briefly review such ab initio methods that can be applied to calculate the electronic and optical properties of very small nanocrystals, with extra emphasis on density functional theory (DFT) and time-dependent DFT which are the most suitable approaches for the description of these systems. Finally, we present our recent results on this topic where we investigated the applicability of nanodiamonds and silicon carbide nanocrystals for in vivo bioimaging. (topical review)

  15. Computational Design of Biomimetic Phosphate Scavengers

    DEFF Research Database (Denmark)

    Gruber, Mathias Felix; Wood, Elizabeth Baker; Truelsen, Sigurd Friis

    2015-01-01

    Phosphorus has long been the target of much research, but in recent years the focus has shifted from being limited only to reducing its detrimental environmental impact, to also looking at how it is linked to the global food security. Therefore, the interest in finding novel techniques for phosph......Phosphorus has long been the target of much research, but in recent years the focus has shifted from being limited only to reducing its detrimental environmental impact, to also looking at how it is linked to the global food security. Therefore, the interest in finding novel techniques...... for phosphorus recovery, as well as improving existing techniques, has increased. In this study we apply a hybrid simulation approach of molecular dynamics and quantum mechanics to investigate the binding modes of phosphate anions by a small intrinsically disordered peptide. Our results confirm...... phosphate could be the starting point of new novel technological approaches toward phosphorus recovery, and they represent an excellent model system for investigating the nature and dynamics of functional de novo designed intrinsically disordered proteins....

  16. Deep Learning for Drug Design: an Artificial Intelligence Paradigm for Drug Discovery in the Big Data Era.

    Science.gov (United States)

    Jing, Yankang; Bian, Yuemin; Hu, Ziheng; Wang, Lirong; Xie, Xiang-Qun Sean

    2018-03-30

    Over the last decade, deep learning (DL) methods have been extremely successful and widely used to develop artificial intelligence (AI) in almost every domain, especially after it achieved its proud record on computational Go. Compared to traditional machine learning (ML) algorithms, DL methods still have a long way to go to achieve recognition in small molecular drug discovery and development. And there is still lots of work to do for the popularization and application of DL for research purpose, e.g., for small molecule drug research and development. In this review, we mainly discussed several most powerful and mainstream architectures, including the convolutional neural network (CNN), recurrent neural network (RNN), and deep auto-encoder networks (DAENs), for supervised learning and nonsupervised learning; summarized most of the representative applications in small molecule drug design; and briefly introduced how DL methods were used in those applications. The discussion for the pros and cons of DL methods as well as the main challenges we need to tackle were also emphasized.

  17. Regulatory RNA design through evolutionary computation and strand displacement.

    Science.gov (United States)

    Rostain, William; Landrain, Thomas E; Rodrigo, Guillermo; Jaramillo, Alfonso

    2015-01-01

    The discovery and study of a vast number of regulatory RNAs in all kingdoms of life over the past decades has allowed the design of new synthetic RNAs that can regulate gene expression in vivo. Riboregulators, in particular, have been used to activate or repress gene expression. However, to accelerate and scale up the design process, synthetic biologists require computer-assisted design tools, without which riboregulator engineering will remain a case-by-case design process requiring expert attention. Recently, the design of RNA circuits by evolutionary computation and adapting strand displacement techniques from nanotechnology has proven to be suited to the automated generation of DNA sequences implementing regulatory RNA systems in bacteria. Herein, we present our method to carry out such evolutionary design and how to use it to create various types of riboregulators, allowing the systematic de novo design of genetic control systems in synthetic biology.

  18. Integration of rocket turbine design and analysis through computer graphics

    Science.gov (United States)

    Hsu, Wayne; Boynton, Jim

    1988-01-01

    An interactive approach with engineering computer graphics is used to integrate the design and analysis processes of a rocket engine turbine into a progressive and iterative design procedure. The processes are interconnected through pre- and postprocessors. The graphics are used to generate the blade profiles, their stacking, finite element generation, and analysis presentation through color graphics. Steps of the design process discussed include pitch-line design, axisymmetric hub-to-tip meridional design, and quasi-three-dimensional analysis. The viscous two- and three-dimensional analysis codes are executed after acceptable designs are achieved and estimates of initial losses are confirmed.

  19. A Novel Design for Drug-Drug Interaction Alerts Improves Prescribing Efficiency.

    Science.gov (United States)

    Russ, Alissa L; Chen, Siying; Melton, Brittany L; Johnson, Elizabette G; Spina, Jeffrey R; Weiner, Michael; Zillich, Alan J

    2015-09-01

    Drug-drug interactions (DDIs) are common in clinical care and pose serious risks for patients. Electronic health records display DDI alerts that can influence prescribers, but the interface design of DDI alerts has largely been unstudied. In this study, the objective was to apply human factors engineering principles to alert design. It was hypothesized that redesigned DDI alerts would significantly improve prescribers' efficiency and reduce prescribing errors. In a counterbalanced, crossover study with prescribers, two DDI alert designs were evaluated. Department of Veterans Affairs (VA) prescribers were video recorded as they completed fictitious patient scenarios, which included DDI alerts of varying severity. Efficiency was measured from time-stamped recordings. Prescribing errors were evaluated against predefined criteria. Efficiency and prescribing errors were analyzed with the Wilcoxon signed-rank test. Other usability data were collected on the adequacy of alert content, prescribers' use of the DDI monograph, and alert navigation. Twenty prescribers completed patient scenarios for both designs. Prescribers resolved redesigned alerts in about half the time (redesign: 52 seconds versus original design: 97 seconds; p<.001). Prescribing errors were not significantly different between the two designs. Usability results indicate that DDI alerts might be enhanced by facilitating easier access to laboratory data and dosing information and by allowing prescribers to cancel either interacting medication directly from the alert. Results also suggest that neither design provided adequate information for decision making via the primary interface. Applying human factors principles to DDI alerts improved overall efficiency. Aspects of DDI alert design that could be further enhanced prior to implementation were also identified.

  20. DR2DI: a powerful computational tool for predicting novel drug-disease associations

    Science.gov (United States)

    Lu, Lu; Yu, Hua

    2018-05-01

    Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

  1. DR2DI: a powerful computational tool for predicting novel drug-disease associations

    Science.gov (United States)

    Lu, Lu; Yu, Hua

    2018-04-01

    Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

  2. A Generative Computer Model for Preliminary Design of Mass Housing

    Directory of Open Access Journals (Sweden)

    Ahmet Emre DİNÇER

    2014-05-01

    Full Text Available Today, we live in what we call the “Information Age”, an age in which information technologies are constantly being renewed and developed. Out of this has emerged a new approach called “Computational Design” or “Digital Design”. In addition to significantly influencing all fields of engineering, this approach has come to play a similar role in all stages of the design process in the architectural field. In providing solutions for analytical problems in design such as cost estimate, circulation systems evaluation and environmental effects, which are similar to engineering problems, this approach is being used in the evaluation, representation and presentation of traditionally designed buildings. With developments in software and hardware technology, it has evolved as the studies based on design of architectural products and production implementations with digital tools used for preliminary design stages. This paper presents a digital model which may be used in the preliminary stage of mass housing design with Cellular Automata, one of generative design systems based on computational design approaches. This computational model, developed by scripts of 3Ds Max software, has been implemented on a site plan design of mass housing, floor plan organizations made by user preferences and facade designs. By using the developed computer model, many alternative housing types could be rapidly produced. The interactive design tool of this computational model allows the user to transfer dimensional and functional housing preferences by means of the interface prepared for model. The results of the study are discussed in the light of innovative architectural approaches.

  3. Advanced Simulation and Computing Co-Design Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Ang, James A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hoang, Thuc T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kelly, Suzanne M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); McPherson, Allen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Neely, Rob [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-11-01

    This ASC Co-design Strategy lays out the full continuum and components of the co-design process, based on what we have experienced thus far and what we wish to do more in the future to meet the program’s mission of providing high performance computing (HPC) and simulation capabilities for NNSA to carry out its stockpile stewardship responsibility.

  4. Computer Game Design Classes: The Students' and Professionals' Perspectives

    Science.gov (United States)

    Swacha, Jakub; Skrzyszewski, Adam; Syslo, Wojciech A.

    2010-01-01

    There are multiple reasons that justify teaching computer game design. Its multi-aspectual nature creates opportunity to develop, at the same time, creativity, technical skills and ability to work in team. Thinking of game design classes, one needs direction on what to focus on so that the students could benefit the most. In this paper, we present…

  5. DEVELOPMENT OF COMPUTER AIDED DESIGN OF CHAIN COUPLING

    Directory of Open Access Journals (Sweden)

    Sergey Aleksandrovich Sergeev

    2015-12-01

    Full Text Available The present paper describes the development stages of computer-aided design of chain couplings. The first stage is the automation of traditional design techniques (intermediate automation. The second integrated automation with the development of automated equipment and production technology, including on the basis of flexible manufacturing systems (high level of automation.

  6. Computer-Aided Test Flow in Core-Based Design

    NARCIS (Netherlands)

    Zivkovic, V.; Tangelder, R.J.W.T.; Kerkhoff, Hans G.

    2000-01-01

    This paper copes with the test-pattern generation and fault coverage determination in the core based design. The basic core-test strategy that one has to apply in the core-based design is stated in this work. A Computer-Aided Test (CAT) flow is proposed resulting in accurate fault coverage of

  7. Issues in Text Design and Layout for Computer Based Communications.

    Science.gov (United States)

    Andresen, Lee W.

    1991-01-01

    Discussion of computer-based communications (CBC) focuses on issues involved with screen design and layout for electronic text, based on experiences with electronic messaging, conferencing, and publishing within the Australian Open Learning Information Network (AOLIN). Recommendations for research on design and layout for printed text are also…

  8. A solar powered wireless computer mouse: industrial design concepts

    NARCIS (Netherlands)

    Reich, N.H.; Veefkind, M.; van Sark, W.G.J.H.M.; Alsema, E.A.; Turkenburg, W.C.; Silvester, S.

    2009-01-01

    A solar powered wireless computer mouse (SPM) was chosen to serve as a case study for the evaluation and optimization of industrial design processes of photovoltaic (PV) powered consumer systems. As the design process requires expert knowledge in various technical fields, we assessed and compared

  9. Modern Prodrug Design for Targeted Oral Drug Delivery

    Directory of Open Access Journals (Sweden)

    Arik Dahan

    2014-10-01

    Full Text Available The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options.

  10. 75 FR 52780 - Designation of Nine Counties as High Intensity Drug Trafficking Areas

    Science.gov (United States)

    2010-08-27

    ... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Nine Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated nine additional counties as High Drug Trafficking Areas pursuant to...

  11. 75 FR 21368 - Designation of Five Counties as High Intensity Drug Trafficking Areas

    Science.gov (United States)

    2010-04-23

    ... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Five Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated five additional counties as High Drug Trafficking Areas pursuant to...

  12. Computer organization and design the hardware/software interface

    CERN Document Server

    Patterson, David A

    2009-01-01

    The classic textbook for computer systems analysis and design, Computer Organization and Design, has been thoroughly updated to provide a new focus on the revolutionary change taking place in industry today: the switch from uniprocessor to multicore microprocessors. This new emphasis on parallelism is supported by updates reflecting the newest technologies with examples highlighting the latest processor designs, benchmarking standards, languages and tools. As with previous editions, a MIPS processor is the core used to present the fundamentals of hardware technologies, assembly language, compu

  13. Computer-integrated design and information management for nuclear projects

    International Nuclear Information System (INIS)

    Gonzalez, A.; Martin-Guirado, L.; Nebrera, F.

    1987-01-01

    Over the past seven years, Empresarios Agrupados has been developing a comprehensive, computer-integrated system to perform the majority of the engineering, design, procurement and construction management activities in nuclear, fossil-fired as well as hydro power plant projects. This system, which is already in a production environment, comprises a large number of computer programs and data bases designed using a modular approach. Each software module, dedicated to meeting the needs of a particular design group or project discipline, facilitates the performance of functional tasks characteristic of the power plant engineering process

  14. HIV protease drug resistance and its impact on inhibitor design.

    Science.gov (United States)

    Ala, P J; Rodgers, J D; Chang, C H

    1999-07-01

    The primary cause of resistance to the currently available HIV protease inhibitors is the accumulation of multiple mutations in the viral protease. So far more than 20 substitutions have been observed in the active site, dimer interface, surface loops and flaps of the homodimer. While many mutations reduce the protease's affinity for inhibitors, others appear to enhance its catalytic efficiency. This high degree of genetic flexibility has made the protease an elusive drug target. The design of the next generation of HIV protease inhibitors will be discussed in light of the current structural information.

  15. Computer Aided Design System for Developing Musical Fountain Programs

    Institute of Scientific and Technical Information of China (English)

    刘丹; 张乃尧; 朱汉城

    2003-01-01

    A computer aided design system for developing musical fountain programs was developed with multiple functions such as intelligent design, 3-D animation, manual modification and synchronized motion to make the development process more efficient. The system first analyzed the music form and sentiment using many basic features of the music to select a basic fountain program. Then, this program is simulated with 3-D animation and modified manually to achieve the desired results. Finally, the program is transformed to a computer control program to control the musical fountain in time with the music. A prototype system for the musical fountain was also developed. It was tested with many styles of music and users were quite satisfied with its performance. By integrating various functions, the proposed computer aided design system for developing musical fountain programs greatly simplified the design of the musical fountain programs.

  16. An adaptive drug delivery design using neural networks for effective treatment of infectious diseases: a simulation study.

    Science.gov (United States)

    Padhi, Radhakant; Bhardhwaj, Jayender R

    2009-06-01

    An adaptive drug delivery design is presented in this paper using neural networks for effective treatment of infectious diseases. The generic mathematical model used describes the coupled evolution of concentration of pathogens, plasma cells, antibodies and a numerical value that indicates the relative characteristic of a damaged organ due to the disease under the influence of external drugs. From a system theoretic point of view, the external drugs can be interpreted as control inputs, which can be designed based on control theoretic concepts. In this study, assuming a set of nominal parameters in the mathematical model, first a nonlinear controller (drug administration) is designed based on the principle of dynamic inversion. This nominal drug administration plan was found to be effective in curing "nominal model patients" (patients whose immunological dynamics conform to the mathematical model used for the control design exactly. However, it was found to be ineffective in curing "realistic model patients" (patients whose immunological dynamics may have off-nominal parameter values and possibly unwanted inputs) in general. Hence, to make the drug delivery dosage design more effective for realistic model patients, a model-following adaptive control design is carried out next by taking the help of neural networks, that are trained online. Simulation studies indicate that the adaptive controller proposed in this paper holds promise in killing the invading pathogens and healing the damaged organ even in the presence of parameter uncertainties and continued pathogen attack. Note that the computational requirements for computing the control are very minimal and all associated computations (including the training of neural networks) can be carried out online. However it assumes that the required diagnosis process can be carried out at a sufficient faster rate so that all the states are available for control computation.

  17. Design and analysis of sustainable computer mouse using design for disassembly methodology

    Science.gov (United States)

    Roni Sahroni, Taufik; Fitri Sukarman, Ahmad; Agung Mahardini, Karunia

    2017-12-01

    This paper presents the design and analysis of computer mouse using Design for Disassembly methodology. Basically, the existing computer mouse model consist a number of unnecessary part that cause the assembly and disassembly time in production. The objective of this project is to design a new computer mouse based on Design for Disassembly (DFD) methodology. The main methodology of this paper was proposed from sketch generation, concept selection, and concept scoring. Based on the design screening, design concept B was selected for further analysis. New design of computer mouse is proposed using fastening system. Furthermore, three materials of ABS, Polycarbonate, and PE high density were prepared to determine the environmental impact category. Sustainable analysis was conducted using software SolidWorks. As a result, PE High Density gives the lowers amount in the environmental category with great maximum stress value.

  18. Computer-delivered indirect screening and brief intervention for drug use in the perinatal period: A randomized trial.

    Science.gov (United States)

    Ondersma, Steven J; Svikis, Dace S; Thacker, Casey; Resnicow, Ken; Beatty, Jessica R; Janisse, James; Puder, Karoline

    2018-04-01

    Under-reporting of drug use in the perinatal period is well-documented, and significantly limits the reach of proactive intervention approaches. The Wayne Indirect Drug Use Screener (WIDUS) focuses on correlates of drug use rather than use itself. This trial tested a computer-delivered, brief intervention designed for use with indirect screen-positive cases, seeking to motivate reductions in drug use without presuming its presence. Randomized clinical trial with 500 WIDUS-positive postpartum women recruited between August 14, 2012 and November 19, 2014. Participants were randomly assigned to either a time control condition or a single-session, tailored, indirect brief intervention. The primary outcome was days of drug use over the 6-month follow-up period; secondary outcomes included urine and hair analyses results at 3- and 6-month follow-up. All outcomes were measured by blinded evaluators. Of the 500 participants (252 intervention and 248 control), 36.1% of participants acknowledged drug use in the 3 months prior to pregnancy, but 89% tested positive at the 6-month follow-up. Participants rated the intervention as easy to use (4.9/5) and helpful (4.4/5). Analyses revealed no between-group differences in drug use (52% in the intervention group, vs. 53% among controls; OR 1.03). Exploratory analyses also showed that intervention effects were not moderated by baseline severity, WIDUS score, or readiness to change. The present trial showed no evidence of efficacy for an indirect, single-session, computer-delivered, brief intervention designed as a complement to indirect screening. More direct approaches that still do not presume active drug use may be possible and appropriate. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Intelligent computer systems in engineering design principles and applications

    CERN Document Server

    Sunnersjo, Staffan

    2016-01-01

    This introductory book discusses how to plan and build useful, reliable, maintainable and cost efficient computer systems for automated engineering design. The book takes a user perspective and seeks to bridge the gap between texts on principles of computer science and the user manuals for commercial design automation software. The approach taken is top-down, following the path from definition of the design task and clarification of the relevant design knowledge to the development of an operational system well adapted for its purpose. This introductory text for the practicing engineer working in industry covers most vital aspects of planning such a system. Experiences from applications of automated design systems in practice are reviewed based on a large number of real, industrial cases. The principles behind the most popular methods in design automation are presented with sufficient rigour to give the user confidence in applying them on real industrial problems. This book is also suited for a half semester c...

  20. CRITICAL ASSESSMENT OF CONTRIBUTION FROM INDIAN PUBLICATIONS: THE ROLE OF IN SILICO DESIGNING METHODS LEADING TO DRUGS OR DRUG-LIKE COMPOUNDS USING TEXT BASED MINING AND ASSOCIATION

    Directory of Open Access Journals (Sweden)

    Pawan Kumar

    2017-09-01

    Full Text Available Over the several decades, India is constantly challenged by communicable and non-communicable diseases which are originated either by poor lifestyle or by environmental factors. The pools of diseases are constantly posing serious threats to mankind especially among the poverty-stricken families. Scientific communities across the globe are working continuously to design drug molecules to overcome the burden of these life threaten diseases. In last three decades, many computational algorithms and tools have been developed to identify potential drug targets and their inhibitors. It is believed that computational techniques have reduced the time and money required to develop an inhibitor into drug. However, applicability and deliverability of these in silico techniques in rational drug designing are not fully evaluated. In the present study, PubMed/Medline extracted data driven analysis has been performed to highlight the influence and progress of the theoretical methods in the field of drug discovery across India and compared with the world. Drug discovery related keyword dictionary has been built and utilized to select only drug discovery related PubMed abstract. A second keyword set (related to bioinformatics tools is used for normalized pointwise mutual information (PMI based association analysis. Observations show that drug discovery has been an interdisciplinary research and used many tools starting with QSAR, docking, pharmacophore, Molecular Simulations etc. The publications contributed from India (2% are similar as compared to the contribution in total world publications, suggesting large scope in future. Data coverage as represented since 1990-2015 in PubMed as indicated by number of publications associated with drug discovery is almost same in world and India (~75%. Emerging institutes/Universities are contributing since last 10 years as observed from Indian publication list. However, this method has many limitations as discussed.

  1. SWEETLEAD: an in silico database of approved drugs, regulated chemicals, and herbal isolates for computer-aided drug discovery.

    Directory of Open Access Journals (Sweden)

    Paul A Novick

    Full Text Available In the face of drastically rising drug discovery costs, strategies promising to reduce development timelines and expenditures are being pursued. Computer-aided virtual screening and repurposing approved drugs are two such strategies that have shown recent success. Herein, we report the creation of a highly-curated in silico database of chemical structures representing approved drugs, chemical isolates from traditional medicinal herbs, and regulated chemicals, termed the SWEETLEAD database. The motivation for SWEETLEAD stems from the observance of conflicting information in publicly available chemical databases and the lack of a highly curated database of chemical structures for the globally approved drugs. A consensus building scheme surveying information from several publicly accessible databases was employed to identify the correct structure for each chemical. Resulting structures are filtered for the active pharmaceutical ingredient, standardized, and differing formulations of the same drug were combined in the final database. The publically available release of SWEETLEAD (https://simtk.org/home/sweetlead provides an important tool to enable the successful completion of computer-aided repurposing and drug discovery campaigns.

  2. An overview of interactive computer graphics and its application to computer-aided engineering and design

    International Nuclear Information System (INIS)

    Van Dam, A.

    1983-01-01

    The purpose of this brief birds-eye view of interactive graphics is to list the key ideas, and to show how one of the most important application areas, Computer Aided Engineering/Design takes advantage of it. (orig.)

  3. SHIPBUILDING PRODUCTION PROCESS DESIGN METHODOLOGY USING COMPUTER SIMULATION

    OpenAIRE

    Marko Hadjina; Nikša Fafandjel; Tin Matulja

    2015-01-01

    In this research a shipbuilding production process design methodology, using computer simulation, is suggested. It is expected from suggested methodology to give better and more efficient tool for complex shipbuilding production processes design procedure. Within the first part of this research existing practice for production process design in shipbuilding was discussed, its shortcomings and problem were emphasized. In continuing, discrete event simulation modelling method, as basis of sugge...

  4. Low energy nanoemulsification to design veterinary controlled drug delivery devices

    Directory of Open Access Journals (Sweden)

    Thierry F Vandamme

    2010-10-01

    Full Text Available Thierry F Vandamme, Nicolas Anton, University of Strasbourg, Faculty of Pharmacy, Illkirch Cedex, France; UMR CNRS 7199, Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique, Illkirch Cedex, France,  This work is selected as Controlled Release Society Outstanding Veterinary Paper Award 2010Abstract: The unique properties of nanomaterials related to structural stability and quantum-scale reactive properties open up a world of possibilities that could be exploited to design and to target drug delivery or create truly microscale biological sensors for veterinary applications. We developed cost-saving and solvent-free nanoemulsions. Formulated with a low-energy method, these nanoemulsions can find application in the delivery of controlled amounts of drugs into the beverage of breeding animals (such as poultry, cattle, pigs or be used for the controlled release of injectable poorly water-soluble drugs.Keywords: nanoemulsion, nanomedicine, low-energy emulsification, veterinary, ketoprofen, sulfamethazine

  5. Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

    Science.gov (United States)

    Guedes, Karen Marinho Maciel; Borges, Rosivaldo Santos; Fontes-Júnior, Enéas Andrade; Silva, Andressa Santa Brigida; Fernandes, Luanna Melo Pereira; Cartágenes, Sabrina Carvalho; Pinto, Ana Carla Godinho; Silva, Mallone Lopes; Queiroz, Luana Melo Diogo; Vieira, José Luís Fernandes; Sousa, Pergentino José Cunha; Maia, Cristiane Socorro Ferraz

    2018-04-13

    Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

  6. The Evolution of Computer Based Learning Software Design: Computer Assisted Teaching Unit Experience.

    Science.gov (United States)

    Blandford, A. E.; Smith, P. R.

    1986-01-01

    Describes the style of design of computer simulations developed by Computer Assisted Teaching Unit at Queen Mary College with reference to user interface, input and initialization, input data vetting, effective display screen use, graphical results presentation, and need for hard copy. Procedures and problems relating to academic involvement are…

  7. Development of integrated platform for computational material design

    Energy Technology Data Exchange (ETDEWEB)

    Kiyoshi, Matsubara; Kumi, Itai; Nobutaka, Nishikawa; Akifumi, Kato [Center for Computational Science and Engineering, Fuji Research Institute Corporation (Japan); Hideaki, Koike [Advance Soft Corporation (Japan)

    2003-07-01

    The goal of our project is to design and develop a problem-solving environment (PSE) that will help computational scientists and engineers develop large complicated application software and simulate complex phenomena by using networking and parallel computing. The integrated platform, which is designed for PSE in the Japanese national project of Frontier Simulation Software for Industrial Science, is defined by supporting the entire range of problem solving activity from program formulation and data setup to numerical simulation, data management, and visualization. A special feature of our integrated platform is based on a new architecture called TASK FLOW. It integrates the computational resources such as hardware and software on the network and supports complex and large-scale simulation. This concept is applied to computational material design and the project 'comprehensive research for modeling, analysis, control, and design of large-scale complex system considering properties of human being'. Moreover this system will provide the best solution for developing large and complicated software and simulating complex and large-scaled phenomena in computational science and engineering. A prototype has already been developed and the validation and verification of an integrated platform will be scheduled by using the prototype in 2003. In the validation and verification, fluid-structure coupling analysis system for designing an industrial machine will be developed on the integrated platform. As other examples of validation and verification, integrated platform for quantum chemistry and bio-mechanical system are planned.

  8. Development of integrated platform for computational material design

    International Nuclear Information System (INIS)

    Kiyoshi, Matsubara; Kumi, Itai; Nobutaka, Nishikawa; Akifumi, Kato; Hideaki, Koike

    2003-01-01

    The goal of our project is to design and develop a problem-solving environment (PSE) that will help computational scientists and engineers develop large complicated application software and simulate complex phenomena by using networking and parallel computing. The integrated platform, which is designed for PSE in the Japanese national project of Frontier Simulation Software for Industrial Science, is defined by supporting the entire range of problem solving activity from program formulation and data setup to numerical simulation, data management, and visualization. A special feature of our integrated platform is based on a new architecture called TASK FLOW. It integrates the computational resources such as hardware and software on the network and supports complex and large-scale simulation. This concept is applied to computational material design and the project 'comprehensive research for modeling, analysis, control, and design of large-scale complex system considering properties of human being'. Moreover this system will provide the best solution for developing large and complicated software and simulating complex and large-scaled phenomena in computational science and engineering. A prototype has already been developed and the validation and verification of an integrated platform will be scheduled by using the prototype in 2003. In the validation and verification, fluid-structure coupling analysis system for designing an industrial machine will be developed on the integrated platform. As other examples of validation and verification, integrated platform for quantum chemistry and bio-mechanical system are planned

  9. FOREWORD: Computational methodologies for designing materials Computational methodologies for designing materials

    Science.gov (United States)

    Rahman, Talat S.

    2009-02-01

    It would be fair to say that in the past few decades, theory and computer modeling have played a major role in elucidating the microscopic factors that dictate the properties of functional novel materials. Together with advances in experimental techniques, theoretical methods are becoming increasingly capable of predicting properties of materials at different length scales, thereby bringing in sight the long-sought goal of designing material properties according to need. Advances in computer technology and their availability at a reasonable cost around the world have made tit all the more urgent to disseminate what is now known about these modern computational techniques. In this special issue on computational methodologies for materials by design we have tried to solicit articles from authors whose works collectively represent the microcosm of developments in the area. This turned out to be a difficult task for a variety of reasons, not the least of which is space limitation in this special issue. Nevertheless, we gathered twenty articles that represent some of the important directions in which theory and modeling are proceeding in the general effort to capture the ability to produce materials by design. The majority of papers presented here focus on technique developments that are expected to uncover further the fundamental processes responsible for material properties, and for their growth modes and morphological evolutions. As for material properties, some of the articles here address the challenges that continue to emerge from attempts at accurate descriptions of magnetic properties, of electronically excited states, and of sparse matter, all of which demand new looks at density functional theory (DFT). I should hasten to add that much of the success in accurate computational modeling of materials emanates from the remarkable predictive power of DFT, without which we would not be able to place the subject on firm theoretical grounds. As we know and will also

  10. Collaborative virtual reality environments for computational science and design

    International Nuclear Information System (INIS)

    Papka, M. E.

    1998-01-01

    The authors are developing a networked, multi-user, virtual-reality-based collaborative environment coupled to one or more petaFLOPs computers, enabling the interactive simulation of 10 9 atom systems. The purpose of this work is to explore the requirements for this coupling. Through the design, development, and testing of such systems, they hope to gain knowledge that allows computational scientists to discover and analyze their results more quickly and in a more intuitive manner

  11. Architectural design for a topological cluster state quantum computer

    International Nuclear Information System (INIS)

    Devitt, Simon J; Munro, William J; Nemoto, Kae; Fowler, Austin G; Stephens, Ashley M; Greentree, Andrew D; Hollenberg, Lloyd C L

    2009-01-01

    The development of a large scale quantum computer is a highly sought after goal of fundamental research and consequently a highly non-trivial problem. Scalability in quantum information processing is not just a problem of qubit manufacturing and control but it crucially depends on the ability to adapt advanced techniques in quantum information theory, such as error correction, to the experimental restrictions of assembling qubit arrays into the millions. In this paper, we introduce a feasible architectural design for large scale quantum computation in optical systems. We combine the recent developments in topological cluster state computation with the photonic module, a simple chip-based device that can be used as a fundamental building block for a large-scale computer. The integration of the topological cluster model with this comparatively simple operational element addresses many significant issues in scalable computing and leads to a promising modular architecture with complete integration of active error correction, exhibiting high fault-tolerant thresholds.

  12. Design and applications of Computed Industrial Tomographic Imaging System (CITIS)

    International Nuclear Information System (INIS)

    Ramakrishna, G.S.; Umesh Kumar; Datta, S.S.; Rao, S.M.

    1996-01-01

    Computed tomographic imaging is an advanced technique for nondestructive testing (NDT) and examination. For the first time in India a computed aided tomography system has been indigenously developed in BARC for testing industrial components and was successfully demonstrated. The system in addition to Computed Tomography (CT) can also perform Digital Radiography (DR) to serve as a powerful tool for NDT applications. It has wider applications in the fields of nuclear, space and allied fields. The authors have developed a computed industrial tomographic imaging system with Cesium 137 gamma radiation source for nondestructive examination of engineering and industrial specimens. This presentation highlights the design and development of a prototype system and its software for image reconstruction, simulation and display. The paper also describes results obtained with several tests specimens, current development and possibility of using neutrons as well as high energy x-rays in computed tomography. (author)

  13. Accident sequence analysis of human-computer interface design

    International Nuclear Information System (INIS)

    Fan, C.-F.; Chen, W.-H.

    2000-01-01

    It is important to predict potential accident sequences of human-computer interaction in a safety-critical computing system so that vulnerable points can be disclosed and removed. We address this issue by proposing a Multi-Context human-computer interaction Model along with its analysis techniques, an Augmented Fault Tree Analysis, and a Concurrent Event Tree Analysis. The proposed augmented fault tree can identify the potential weak points in software design that may induce unintended software functions or erroneous human procedures. The concurrent event tree can enumerate possible accident sequences due to these weak points

  14. The Architectural Designs of a Nanoscale Computing Model

    Directory of Open Access Journals (Sweden)

    Mary M. Eshaghian-Wilner

    2004-08-01

    Full Text Available A generic nanoscale computing model is presented in this paper. The model consists of a collection of fully interconnected nanoscale computing modules, where each module is a cube of cells made out of quantum dots, spins, or molecules. The cells dynamically switch between two states by quantum interactions among their neighbors in all three dimensions. This paper includes a brief introduction to the field of nanotechnology from a computing point of view and presents a set of preliminary architectural designs for fabricating the nanoscale model studied.

  15. High-End Computing Challenges in Aerospace Design and Engineering

    Science.gov (United States)

    Bailey, F. Ronald

    2004-01-01

    High-End Computing (HEC) has had significant impact on aerospace design and engineering and is poised to make even more in the future. In this paper we describe four aerospace design and engineering challenges: Digital Flight, Launch Simulation, Rocket Fuel System and Digital Astronaut. The paper discusses modeling capabilities needed for each challenge and presents projections of future near and far-term HEC computing requirements. NASA's HEC Project Columbia is described and programming strategies presented that are necessary to achieve high real performance.

  16. Computational Design of Batteries from Materials to Systems

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Kandler A [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Santhanagopalan, Shriram [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Yang, Chuanbo [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Graf, Peter A [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Usseglio Viretta, Francois L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Li, Qibo [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Finegan, Donal [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Pesaran, Ahmad A [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Yao, Koffi (Pierre) [Argonne National Laboratory; Abraham, Daniel [Argonne National Laboratory; Dees, Dennis [Argonne National Laboratory; Jansen, Andy [Argonne National Laboratory; Mukherjee, Partha [Texas A& M University; Mistry, Aashutosh [Texas A& M University; Verma, Ankit [Texas A& M University; Lamb, Josh [Sandia National Laboratories; Darcy, Eric [NASA

    2017-09-01

    Computer models are helping to accelerate the design and validation of next generation batteries and provide valuable insights not possible through experimental testing alone. Validated 3-D physics-based models exist for predicting electrochemical performance, thermal and mechanical response of cells and packs under normal and abuse scenarios. The talk describes present efforts to make the models better suited for engineering design, including improving their computation speed, developing faster processes for model parameter identification including under aging, and predicting the performance of a proposed electrode material recipe a priori using microstructure models.

  17. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

    Directory of Open Access Journals (Sweden)

    R Pignatello

    2011-01-01

    Full Text Available Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy.

  18. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    Science.gov (United States)

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  19. Giga-voxel computational morphogenesis for structural design

    DEFF Research Database (Denmark)

    Aage, Niels; Andreassen, Erik; Lazarov, Boyan Stefanov

    2017-01-01

    In the design of industrial products ranging from hearing aidsto automobiles and aeroplanes, material is distributed so as to maximize the performance and minimize the cost. Historically, human intuition and insight have driven the evolution of mechanical design, recently assisted by computer...... aeroplane wing designs, which translates into are duction in fuel consumption of about 40–200 tonnes per year per aeroplane. Our morphogenesis process is generally applicable, not only to mechanical design, but also to flow systems3, antennas4,nano-optics5 and micro-systems6,7...

  20. The computer-aided design of rubber-metal products

    Directory of Open Access Journals (Sweden)

    Pavlo S. Shvets

    2015-12-01

    Full Text Available The important problem in design of rubber-metal products is the optimization of their mass without sacrificing of proportionality factor is in the limits of standard. Aim: The aim of this work is to improve the computer-aided systems by development and implementation of improved optimization method in rubber-metal CAD systems for designers based on the reverse optimization. Materials and Methods: The paper studies the matters of computer-aided structural design of technical composite products composed of anisotropic materials that are essentially different in properties. Results: The structure of CAD systems for designers solving the problems of such design is offered and the work principles of its subsystems are described. It is shown that complicated systems optimization in CAD systems must consider as restrictions the entitative connection between separate elements of these systems within the area of the optimizing arguments. Conclusions: The problem of the “reverse” optimization when objective functions are the connectivity area parameters is considered. In many cases, this allows receiving solutions that are more effective during the computer-aided design process. The developed CAD system for designers was used during the production of rubber-metal shock absorbers at the Odessa Rubber Technical Articles Plant. The positive technical and economic effect was obtained.

  1. Computer-Aided Chemical Product Design Framework: Design of High Performance and Environmentally Friendly Refrigerants

    DEFF Research Database (Denmark)

    Cignitti, Stefano; Zhang, Lei; Gani, Rafiqul

    properties and needs should carefully be selected for a given heat pump cycle to ensure that an optimum refrigerant is found? How can cycle performance and environmental criteria be integrated at the product design stage and not in post-design analysis? Computer-aided product design methods enable...... the possibility of designing novel molecules, mixtures and blends, such as refrigerants through a systematic framework (Cignitti et al., 2015; Yunus et al., 2014). In this presentation a computer-aided framework is presented for chemical product design through mathematical optimization. Here, molecules, mixtures...... and blends, are systematically designed through a decomposition based solution method. Given a problem definition, computer-aided molecular design (CAMD) problem is defined, which is formulated into a mixed integer nonlinear program (MINLP). The decomposed solution method then sequentially divides the MINLP...

  2. Exploiting Large-Scale Drug-Protein Interaction Information for Computational Drug Repurposing

    Science.gov (United States)

    2014-06-20

    studies that have reported antimalarial activities of azole compounds [39-43] lend support to our model predictions. The highest-scored non-malarial...Table 4, verapamil and cimetidine, do not have antimal- arial activities themselves but exhibit synergism when used in combination with antimalarial ... activators . Because of their high frequencies among the antimalarial drugs, according to Eq. 3, the drug-protein interactions contributing most to the

  3. Giga-voxel computational morphogenesis for structural design

    Science.gov (United States)

    Aage, Niels; Andreassen, Erik; Lazarov, Boyan S.; Sigmund, Ole

    2017-10-01

    In the design of industrial products ranging from hearing aids to automobiles and aeroplanes, material is distributed so as to maximize the performance and minimize the cost. Historically, human intuition and insight have driven the evolution of mechanical design, recently assisted by computer-aided design approaches. The computer-aided approach known as topology optimization enables unrestricted design freedom and shows great promise with regard to weight savings, but its applicability has so far been limited to the design of single components or simple structures, owing to the resolution limits of current optimization methods. Here we report a computational morphogenesis tool, implemented on a supercomputer, that produces designs with giga-voxel resolution—more than two orders of magnitude higher than previously reported. Such resolution provides insights into the optimal distribution of material within a structure that were hitherto unachievable owing to the challenges of scaling up existing modelling and optimization frameworks. As an example, we apply the tool to the design of the internal structure of a full-scale aeroplane wing. The optimized full-wing design has unprecedented structural detail at length scales ranging from tens of metres to millimetres and, intriguingly, shows remarkable similarity to naturally occurring bone structures in, for example, bird beaks. We estimate that our optimized design corresponds to a reduction in mass of 2-5 per cent compared to currently used aeroplane wing designs, which translates into a reduction in fuel consumption of about 40-200 tonnes per year per aeroplane. Our morphogenesis process is generally applicable, not only to mechanical design, but also to flow systems, antennas, nano-optics and micro-systems.

  4. Computer aided hydraulic design of axial flow pump impeller

    International Nuclear Information System (INIS)

    Sreedhar, B.K.; Rao, A.S.L.K.; Kumaraswamy, S.

    1994-01-01

    Pumps are the heart of any power plant and hence their design requires great attention. Computers with their potential for rapid computation can be successfully employed in the design and manufacture of these machines. The paper discusses a program developed for the hydraulic design of axial flow pump impeller. The program, written in FORTRAN 77, is interactive and performs the functions of design calculation, drafting and generation of numerical data for blade manufacture. The drafting function, which makes use of the software ACAD, is carried out automatically by means of suitable interface programs. In addition data for blade manufacture is also generated in either the x-y-z or r-θ-z system. (author). 4 refs., 3 figs

  5. Media milling process optimization for manufacture of drug nanoparticles using design of experiments (DOE).

    Science.gov (United States)

    Nekkanti, Vijaykumar; Marwah, Ashwani; Pillai, Raviraj

    2015-01-01

    Design of experiments (DOE), a component of Quality by Design (QbD), is systematic and simultaneous evaluation of process variables to develop a product with predetermined quality attributes. This article presents a case study to understand the effects of process variables in a bead milling process used for manufacture of drug nanoparticles. Experiments were designed and results were computed according to a 3-factor, 3-level face-centered central composite design (CCD). The factors investigated were motor speed, pump speed and bead volume. Responses analyzed for evaluating these effects and interactions were milling time, particle size and process yield. Process validation batches were executed using the optimum process conditions obtained from software Design-Expert® to evaluate both the repeatability and reproducibility of bead milling technique. Milling time was optimized to process variables by applying DOE resulted in considerable decrease in milling time to achieve the desired particle size. The study indicates the applicability of DOE approach to optimize critical process parameters in the manufacture of drug nanoparticles.

  6. Lowering the threshold for computers in early design : some advances in architectural design

    NARCIS (Netherlands)

    Achten, H.H.

    2004-01-01

    The design drawing is an important medium for establishing design support by means of computers. Architects intensively use graphic representations to communicate their design ideas personally, between professionals, and others. In this study, we consider line drawings such as sketches or drawings.

  7. Design of Drug Delivery Methods for the Brain and Central Nervous System

    Science.gov (United States)

    Lueshen, Eric

    Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection

  8. Spaceborne computer executive routine functional design specification. Volume 2: Computer executive design for space station/base

    Science.gov (United States)

    Kennedy, J. R.; Fitzpatrick, W. S.

    1971-01-01

    The computer executive functional system design concepts derived from study of the Space Station/Base are presented. Information Management System hardware configuration as directly influencing the executive design is reviewed. The hardware configuration and generic executive design requirements are considered in detail in a previous report (System Configuration and Executive Requirements Specifications for Reusable Shuttle and Space Station/Base, 9/25/70). This report defines basic system primitives and delineates processes and process control. Supervisor states are considered for describing basic multiprogramming and multiprocessing systems. A high-level computer executive including control of scheduling, allocation of resources, system interactions, and real-time supervisory functions is defined. The description is oriented to provide a baseline for a functional simulation of the computer executive system.

  9. Computer-Aided Test Flow in Core-Based Design

    OpenAIRE

    Zivkovic, V.; Tangelder, R.J.W.T.; Kerkhoff, Hans G.

    2000-01-01

    This paper copes with the test-pattern generation and fault coverage determination in the core based design. The basic core-test strategy that one has to apply in the core-based design is stated in this work. A Computer-Aided Test (CAT) flow is proposed resulting in accurate fault coverage of embedded cores. The CAT now is applied to a few cores within the Philips Core Test Pilot IC project

  10. A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection

    Directory of Open Access Journals (Sweden)

    Jane P. F. Bai

    2017-03-01

    Full Text Available Developing drugs to treat the toxic effects of lethal toxin (LT and edema toxin (ET produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound’s mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection.

  11. Numerical methods design, analysis, and computer implementation of algorithms

    CERN Document Server

    Greenbaum, Anne

    2012-01-01

    Numerical Methods provides a clear and concise exploration of standard numerical analysis topics, as well as nontraditional ones, including mathematical modeling, Monte Carlo methods, Markov chains, and fractals. Filled with appealing examples that will motivate students, the textbook considers modern application areas, such as information retrieval and animation, and classical topics from physics and engineering. Exercises use MATLAB and promote understanding of computational results. The book gives instructors the flexibility to emphasize different aspects--design, analysis, or computer implementation--of numerical algorithms, depending on the background and interests of students. Designed for upper-division undergraduates in mathematics or computer science classes, the textbook assumes that students have prior knowledge of linear algebra and calculus, although these topics are reviewed in the text. Short discussions of the history of numerical methods are interspersed throughout the chapters. The book a...

  12. Design for scalability in 3D computer graphics architectures

    DEFF Research Database (Denmark)

    Holten-Lund, Hans Erik

    2002-01-01

    This thesis describes useful methods and techniques for designing scalable hybrid parallel rendering architectures for 3D computer graphics. Various techniques for utilizing parallelism in a pipelines system are analyzed. During the Ph.D study a prototype 3D graphics architecture named Hybris has...

  13. Computer methods in designing tourist equipment for people with disabilities

    Science.gov (United States)

    Zuzda, Jolanta GraŻyna; Borkowski, Piotr; Popławska, Justyna; Latosiewicz, Robert; Moska, Eleonora

    2017-11-01

    Modern technologies enable disabled people to enjoy physical activity every day. Many new structures are matched individually and created for people who fancy active tourism, giving them wider opportunities for active pastime. The process of creating this type of devices in every stage, from initial design through assessment to validation, is assisted by various types of computer support software.

  14. On Computational Fluid Dynamics Tools in Architectural Design

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Hougaard, Mads; Stærdahl, Jesper Winther

    engineering computational fluid dynamics (CFD) simulation program ANSYS CFX and a CFD based representative program RealFlow are investigated. These two programs represent two types of CFD based tools available for use during phases of an architectural design process. However, as outlined in two case studies...

  15. SIAM Conference on Geometric Design and Computing. Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-03-11

    The SIAM Conference on Geometric Design and Computing attracted 164 domestic and international researchers, from academia, industry, and government. It provided a stimulating forum in which to learn about the latest developments, to discuss exciting new research directions, and to forge stronger ties between theory and applications. Final Report

  16. The Design and Evaluation of Teaching Experiments in Computer Science.

    Science.gov (United States)

    Forcheri, Paola; Molfino, Maria Teresa

    1992-01-01

    Describes a relational model that was developed to provide a framework for the design and evaluation of teaching experiments for the introduction of computer science in secondary schools in Italy. Teacher training is discussed, instructional materials are considered, and use of the model for the evaluation process is described. (eight references)…

  17. Computational approaches in the design of synthetic receptors - A review.

    Science.gov (United States)

    Cowen, Todd; Karim, Kal; Piletsky, Sergey

    2016-09-14

    The rational design of molecularly imprinted polymers (MIPs) has been a major contributor to their reputation as "plastic antibodies" - high affinity robust synthetic receptors which can be optimally designed, and produced for a much reduced cost than their biological equivalents. Computational design has become a routine procedure in the production of MIPs, and has led to major advances in functional monomer screening, selection of cross-linker and solvent, optimisation of monomer(s)-template ratio and selectivity analysis. In this review the various computational methods will be discussed with reference to all the published relevant literature since the end of 2013, with each article described by the target molecule, the computational approach applied (whether molecular mechanics/molecular dynamics, semi-empirical quantum mechanics, ab initio quantum mechanics (Hartree-Fock, Møller-Plesset, etc.) or DFT) and the purpose for which they were used. Detailed analysis is given to novel techniques including analysis of polymer binding sites, the use of novel screening programs and simulations of MIP polymerisation reaction. The further advances in molecular modelling and computational design of synthetic receptors in particular will have serious impact on the future of nanotechnology and biotechnology, permitting the further translation of MIPs into the realms of analytics and medical technology. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Designing Pervasive Computing Technology - In a Nomadic Work Perspective

    DEFF Research Database (Denmark)

    Kristensen, Jannie Friis

    2002-01-01

    In my thesis work I am investigating how the design of pervasive/ubiquitous computing technology, relate to the flexible and individual work practice of nomadic workers. Through empirical studies and with an experimental systems development approach, the work is focused on: a) Supporting...

  19. The ZAP Project: Designing Interactive Computer Tools for Learning Psychology

    Science.gov (United States)

    Hulshof, Casper; Eysink, Tessa; de Jong, Ton

    2006-01-01

    In the ZAP project, a set of interactive computer programs called "ZAPs" was developed. The programs were designed in such a way that first-year students experience psychological phenomena in a vivid and self-explanatory way. Students can either take the role of participant in a psychological experiment, they can experience phenomena themselves,…

  20. GRAPHIC, time-sharing magnet design computer programs at Argonne

    International Nuclear Information System (INIS)

    Lari, R.J.

    1974-01-01

    This paper describes three magnet design computer programs in use at the Zero Gradient Synchrotron of Argonne National Laboratory. These programs are used in the time sharing mode in conjunction with a Tektronix model 4012 graphic display terminal. The first program in called TRIM, the second MAGNET, and the third GFUN. (U.S.)

  1. Computer-Aided Test Flow in Core-Based Design

    NARCIS (Netherlands)

    Zivkovic, V.; Tangelder, R.J.W.T.; Kerkhoff, Hans G.

    2000-01-01

    This paper copes with the efficient test-pattern generation in a core-based design. A consistent Computer-Aided Test (CAT) flow is proposed based on the required core-test strategy. It generates a test-pattern set for the embedded cores with high fault coverage and low DfT area overhead. The CAT

  2. Designing English for Specific Purposes Course for Computer Science Students

    Science.gov (United States)

    Irshad, Isra; Anwar, Behzad

    2018-01-01

    The aim of this study was to design English for Academic Purposes (EAP) course for University students enrolled in the Computer Science Department. For this purpose, academic English language needs of the students were analyzed by using a 5 point Likert scale questionnaire. Additionally, interviews were also conducted with four faculty members of…

  3. Conceptual design of pipe whip restraints using interactive computer analysis

    International Nuclear Information System (INIS)

    Rigamonti, G.; Dainora, J.

    1975-01-01

    Protection against pipe break effects necessitates a complex interaction between failure mode analysis, piping layout, and structural design. Many iterations are required to finalize structural designs and equipment arrangements. The magnitude of the pipe break loads transmitted by the pipe whip restraints to structural embedments precludes the application of conservative design margins. A simplified analytical formulation of the nonlinear dynamic problems associated with pipe whip has been developed and applied using interactive computer analysis techniques. In the dynamic analysis, the restraint and the associated portion of the piping system, are modeled using the finite element lumped mass approach to properly reflect the dynamic characteristics of the piping/restraint system. The analysis is performed as a series of piecewise linear increments. Each of these linear increments is terminated by either formation of plastic conditions or closing/opening of gaps. The stiffness matrix is modified to reflect the changed stiffness characteristics of the system and re-started using the previous boundary conditions. The formation of yield hinges are related to the plastic moment of the section and unloading paths are automatically considered. The conceptual design of the piping/restraint system is performed using interactive computer analysis. The application of the simplified analytical approach with interactive computer analysis results in an order of magnitude reduction in engineering time and computer cost. (Auth.)

  4. Computer Forensics for Graduate Accountants: A Motivational Curriculum Design Approach

    Directory of Open Access Journals (Sweden)

    Grover Kearns

    2010-06-01

    Full Text Available Computer forensics involves the investigation of digital sources to acquire evidence that can be used in a court of law. It can also be used to identify and respond to threats to hosts and systems. Accountants use computer forensics to investigate computer crime or misuse, theft of trade secrets, theft of or destruction of intellectual property, and fraud. Education of accountants to use forensic tools is a goal of the AICPA (American Institute of Certified Public Accountants. Accounting students, however, may not view information technology as vital to their career paths and need motivation to acquire forensic knowledge and skills. This paper presents a curriculum design methodology for teaching graduate accounting students computer forensics. The methodology is tested using perceptions of the students about the success of the methodology and their acquisition of forensics knowledge and skills. An important component of the pedagogical approach is the use of an annotated list of over 50 forensic web-based tools.

  5. Design requirements for ubiquitous computing environments for healthcare professionals.

    Science.gov (United States)

    Bång, Magnus; Larsson, Anders; Eriksson, Henrik

    2004-01-01

    Ubiquitous computing environments can support clinical administrative routines in new ways. The aim of such computing approaches is to enhance routine physical work, thus it is important to identify specific design requirements. We studied healthcare professionals in an emergency room and developed the computer-augmented environment NOSTOS to support teamwork in that setting. NOSTOS uses digital pens and paper-based media as the primary input interface for data capture and as a means of controlling the system. NOSTOS also includes a digital desk, walk-up displays, and sensor technology that allow the system to track documents and activities in the workplace. We propose a set of requirements and discuss the value of tangible user interfaces for healthcare personnel. Our results suggest that the key requirements are flexibility in terms of system usage and seamless integration between digital and physical components. We also discuss how ubiquitous computing approaches like NOSTOS can be beneficial in the medical workplace.

  6. Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery.

    Science.gov (United States)

    Heifetz, Alexander; Southey, Michelle; Morao, Inaki; Townsend-Nicholson, Andrea; Bodkin, Mike J

    2018-01-01

    GPCR modeling approaches are widely used in the hit-to-lead (H2L) and lead optimization (LO) stages of drug discovery. The aims of these modeling approaches are to predict the 3D structures of the receptor-ligand complexes, to explore the key interactions between the receptor and the ligand and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this book chapter, we present a brief survey of key computational approaches integrated with hierarchical GPCR modeling protocol (HGMP) used in hit-to-lead (H2L) and in lead optimization (LO) stages of structure-based drug discovery (SBDD). We outline the differences in modeling strategies used in H2L and LO of SBDD and illustrate how these tools have been applied in three drug discovery projects.

  7. A computer-aided molecular design framework for crystallization solvent design

    DEFF Research Database (Denmark)

    Karunanithi, Arunprakash T.; Achenie, Luke E.K.; Gani, Rafiqul

    2006-01-01

    One of the key decisions in designing solution crystallization processes is the selection of solvents. In this paper, we present a computer-aided molecular design (CAMD) framework for the design and selection of solvents and/or anti-solvents for solution crystallization. The CAMD problem is formu......One of the key decisions in designing solution crystallization processes is the selection of solvents. In this paper, we present a computer-aided molecular design (CAMD) framework for the design and selection of solvents and/or anti-solvents for solution crystallization. The CAMD problem...... solvent molecules. Solvent design and selection for two types of solution crystallization processes namely cooling crystallization and drowning out crystallization are presented. In the first case study, the design of single compound solvent for crystallization of ibuprofen, which is an important...

  8. Integrating aerodynamic surface modeling for computational fluid dynamics with computer aided structural analysis, design, and manufacturing

    Science.gov (United States)

    Thorp, Scott A.

    1992-01-01

    This presentation will discuss the development of a NASA Geometry Exchange Specification for transferring aerodynamic surface geometry between LeRC systems and grid generation software used for computational fluid dynamics research. The proposed specification is based on a subset of the Initial Graphics Exchange Specification (IGES). The presentation will include discussion of how the NASA-IGES standard will accommodate improved computer aided design inspection methods and reverse engineering techniques currently being developed. The presentation is in viewgraph format.

  9. Technology computer aided design simulation for VLSI MOSFET

    CERN Document Server

    Sarkar, Chandan Kumar

    2013-01-01

    Responding to recent developments and a growing VLSI circuit manufacturing market, Technology Computer Aided Design: Simulation for VLSI MOSFET examines advanced MOSFET processes and devices through TCAD numerical simulations. The book provides a balanced summary of TCAD and MOSFET basic concepts, equations, physics, and new technologies related to TCAD and MOSFET. A firm grasp of these concepts allows for the design of better models, thus streamlining the design process, saving time and money. This book places emphasis on the importance of modeling and simulations of VLSI MOS transistors and

  10. Computer Aided Flowsheet Design using Group Contribution Methods

    DEFF Research Database (Denmark)

    Bommareddy, Susilpa; Eden, Mario R.; Gani, Rafiqul

    2011-01-01

    In this paper, a systematic group contribution based framework is presented for synthesis of process flowsheets from a given set of input and output specifications. Analogous to the group contribution methods developed for molecular design, the framework employs process groups to represent...... information of each flowsheet to minimize the computational load and information storage. The design variables for the selected flowsheet(s) are identified through a reverse simulation approach and are used as initial estimates for rigorous simulation to verify the feasibility and performance of the design....

  11. Establishment of computer code system for nuclear reactor design - analysis

    International Nuclear Information System (INIS)

    Subki, I.R.; Santoso, B.; Syaukat, A.; Lee, S.M.

    1996-01-01

    Establishment of computer code system for nuclear reactor design analysis is given in this paper. This establishment is an effort to provide the capability in running various codes from nuclear data to reactor design and promote the capability for nuclear reactor design analysis particularly from neutronics and safety points. This establishment is also an effort to enhance the coordination of nuclear codes application and development existing in various research centre in Indonesia. Very prospective results have been obtained with the help of IAEA technical assistance. (author). 6 refs, 1 fig., 1 tab

  12. Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals.

    Science.gov (United States)

    Amat-Ur-Rasool, Hafsa; Ahmed, Mehboob

    2015-01-01

    Alzheimer's disease (AD), a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh). The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE), an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals) and self-drawn ligands were compared with Food and Drug Administration (FDA) approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

  13. Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals.

    Directory of Open Access Journals (Sweden)

    Hafsa Amat-Ur-Rasool

    Full Text Available Alzheimer's disease (AD, a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh. The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE, an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals and self-drawn ligands were compared with Food and Drug Administration (FDA approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

  14. Computational design of RNAs with complex energy landscapes.

    Science.gov (United States)

    Höner zu Siederdissen, Christian; Hammer, Stefan; Abfalter, Ingrid; Hofacker, Ivo L; Flamm, Christoph; Stadler, Peter F

    2013-12-01

    RNA has become an integral building material in synthetic biology. Dominated by their secondary structures, which can be computed efficiently, RNA molecules are amenable not only to in vitro and in vivo selection, but also to rational, computation-based design. While the inverse folding problem of constructing an RNA sequence with a prescribed ground-state structure has received considerable attention for nearly two decades, there have been few efforts to design RNAs that can switch between distinct prescribed conformations. We introduce a user-friendly tool for designing RNA sequences that fold into multiple target structures. The underlying algorithm makes use of a combination of graph coloring and heuristic local optimization to find sequences whose energy landscapes are dominated by the prescribed conformations. A flexible interface allows the specification of a wide range of design goals. We demonstrate that bi- and tri-stable "switches" can be designed easily with moderate computational effort for the vast majority of compatible combinations of desired target structures. RNAdesign is freely available under the GPL-v3 license. Copyright © 2013 Wiley Periodicals, Inc.

  15. Computer-aided drug discovery [v1; ref status: indexed, http://f1000r.es/5ij

    Directory of Open Access Journals (Sweden)

    Jürgen Bajorath

    2015-08-01

    Full Text Available Computational approaches are an integral part of interdisciplinary drug discovery research. Understanding the science behind computational tools, their opportunities, and limitations is essential to make a true impact on drug discovery at different levels. If applied in a scientifically meaningful way, computational methods improve the ability to identify and evaluate potential drug molecules, but there remain weaknesses in the methods that preclude naïve applications. Herein, current trends in computer-aided drug discovery are reviewed, and selected computational areas are discussed. Approaches are highlighted that aid in the identification and optimization of new drug candidates. Emphasis is put on the presentation and discussion of computational concepts and methods, rather than case studies or application examples. As such, this contribution aims to provide an overview of the current methodological spectrum of computational drug discovery for a broad audience.

  16. Computational design of patterned interfaces using reduced order models

    International Nuclear Information System (INIS)

    Vattre, A.J.; Abdolrahim, N.; Kolluri, K.; Demkowicz, M.J.

    2014-01-01

    Patterning is a familiar approach for imparting novel functionalities to free surfaces. We extend the patterning paradigm to interfaces between crystalline solids. Many interfaces have non-uniform internal structures comprised of misfit dislocations, which in turn govern interface properties. We develop and validate a computational strategy for designing interfaces with controlled misfit dislocation patterns by tailoring interface crystallography and composition. Our approach relies on a novel method for predicting the internal structure of interfaces: rather than obtaining it from resource-intensive atomistic simulations, we compute it using an efficient reduced order model based on anisotropic elasticity theory. Moreover, our strategy incorporates interface synthesis as a constraint on the design process. As an illustration, we apply our approach to the design of interfaces with rapid, 1-D point defect diffusion. Patterned interfaces may be integrated into the microstructure of composite materials, markedly improving performance. (authors)

  17. Computational design and experimental validation of new thermal barrier systems

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Shengmin [Louisiana State Univ., Baton Rouge, LA (United States)

    2015-03-31

    The focus of this project is on the development of a reliable and efficient ab initio based computational high temperature material design method which can be used to assist the Thermal Barrier Coating (TBC) bond-coat and top-coat design. Experimental evaluations on the new TBCs are conducted to confirm the new TBCs’ properties. Southern University is the subcontractor on this project with a focus on the computational simulation method development. We have performed ab initio density functional theory (DFT) method and molecular dynamics simulation on screening the top coats and bond coats for gas turbine thermal barrier coating design and validation applications. For experimental validations, our focus is on the hot corrosion performance of different TBC systems. For example, for one of the top coatings studied, we examined the thermal stability of TaZr2.75O8 and confirmed it’s hot corrosion performance.

  18. Modern drug design: the implication of using artificial neuronal networks and multiple molecular dynamic simulations

    Science.gov (United States)

    Yakovenko, Oleksandr; Jones, Steven J. M.

    2018-01-01

    We report the implementation of molecular modeling approaches developed as a part of the 2016 Grand Challenge 2, the blinded competition of computer aided drug design technologies held by the D3R Drug Design Data Resource (https://drugdesigndata.org/). The challenge was focused on the ligands of the farnesoid X receptor (FXR), a highly flexible nuclear receptor of the cholesterol derivative chenodeoxycholic acid. FXR is considered an important therapeutic target for metabolic, inflammatory, bowel and obesity related diseases (Expert Opin Drug Metab Toxicol 4:523-532, 2015), but in the context of this competition it is also interesting due to the significant ligand-induced conformational changes displayed by the protein. To deal with these conformational changes we employed multiple simulations of molecular dynamics (MD). Our MD-based protocols were top-ranked in estimating the free energy of binding of the ligands and FXR protein. Our approach was ranked second in the prediction of the binding poses where we also combined MD with molecular docking and artificial neural networks. Our approach showed mediocre results for high-throughput scoring of interactions.

  19. [Clinical skills and outcomes of chair-side computer aided design and computer aided manufacture system].

    Science.gov (United States)

    Yu, Q

    2018-04-09

    Computer aided design and computer aided manufacture (CAD/CAM) technology is a kind of oral digital system which is applied to clinical diagnosis and treatment. It overturns the traditional pattern, and provides a solution to restore defect tooth quickly and efficiently. In this paper we mainly discuss the clinical skills of chair-side CAD/CAM system, including tooth preparation, digital impression, the three-dimensional design of prosthesis, numerical control machining, clinical bonding and so on, and review the outcomes of several common kinds of materials at the same time.

  20. Site Identification by Ligand Competitive Saturation (SILCS) simulations for fragment-based drug design.

    Science.gov (United States)

    Faller, Christina E; Raman, E Prabhu; MacKerell, Alexander D; Guvench, Olgun

    2015-01-01

    Fragment-based drug design (FBDD) involves screening low molecular weight molecules ("fragments") that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind nonoverlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR and X-ray crystallography, have proven very useful but can be expensive in terms of time, materials, and labor. Accordingly, a variety of computational FBDD approaches have been developed that provide different levels of detail and accuracy.The Site Identification by Ligand Competitive Saturation (SILCS) method of computational FBDD uses all-atom explicit-solvent molecular dynamics (MD) simulations to identify fragment binding. The target is "soaked" in an aqueous solution with multiple fragments having different identities. The resulting computational competition assay reveals what small molecule types are most likely to bind which regions of the target. From SILCS simulations, 3D probability maps of fragment binding called "FragMaps" can be produced. Based on the probabilities relative to bulk, SILCS FragMaps can be used to determine "Grid Free Energies (GFEs)," which provide per-atom contributions to fragment binding affinities. For essentially no additional computational overhead relative to the production of the FragMaps, GFEs can be used to compute Ligand Grid Free Energies (LGFEs) for arbitrarily complex molecules, and these LGFEs can be used to rank-order the molecules in accordance with binding affinities.

  1. Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

    Science.gov (United States)

    Stegemann, Sven

    2018-06-01

    The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

  2. Computer aided design of nickel-base superalloys

    International Nuclear Information System (INIS)

    Lawrence, P.J.

    1988-01-01

    This paper describes a computer aided design process for Ni-base superalloys developed and employed at ASEA Brown Boveri. The technique involves a series of modules each of which predicts a particular property of a hypothetical new composition. In the first stage of the development of this design techniques modules were produced to predict phase stability, using PHACOMP, and high temperature creep strength and hot corrosion resistance, using multiple linear regression equations derived from the data in the literature. Alloys designed using these technique are also discussed and, in particular, shortcomings of the design process are highlighted. This information was then used to produce a revamped design methodology involving extra modules, including prediction of an alloy's gamma-prime content. (orig.)

  3. Advanced drug delivery systems: Nanotechnology of health design A review

    Directory of Open Access Journals (Sweden)

    Javad Safari

    2014-04-01

    Full Text Available Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.

  4. Reducing constraints on quantum computer design by encoded selective recoupling

    International Nuclear Information System (INIS)

    Lidar, D.A.; Wu, L.-A.

    2002-01-01

    The requirement of performing both single-qubit and two-qubit operations in the implementation of universal quantum logic often leads to very demanding constraints on quantum computer design. We show here how to eliminate the need for single-qubit operations in a large subset of quantum computer proposals: those governed by isotropic and XXZ , XY -type anisotropic exchange interactions. Our method employs an encoding of one logical qubit into two physical qubits, while logic operations are performed using an analogue of the NMR selective recoupling method

  5. Reactor protection system design using micro-computers

    International Nuclear Information System (INIS)

    Fairbrother, D.B.

    1976-01-01

    Reactor protection systems for nuclear power plants have traditionally been built using analog hardware. This hardware works quite well for single parameter trip functions; however, optimum protection against DNBR and KW/ft limits requires more complex trip functions than can easily be handled with analog hardware. For this reason, Babcock and Wilcox has introduced a Reactor Protection System, called the RPS-II, that utilizes a micro-computer to handle the more complex trip functions. The paper describes the design of the RPS-II and the operation of the micro-computer within the Reactor Protection System

  6. Reactor protection system design using micro-computers

    International Nuclear Information System (INIS)

    Fairbrother, D.B.

    1977-01-01

    Reactor Protection Systems for Nuclear Power Plants have traditionally been built using analog hardware. This hardware works quite well for single parameter trip functions; however, optimum protection against DNBR and KW/ft limits requires more complex trip functions than can easily be handled with analog hardware. For this reason, Babcock and Wilcox has introduced a Reactor Protection System, called the RPS-II, that utilizes a micro-computer to handle the more complex trip functions. This paper describes the design of the RPS-II and the operation of the micro-computer within the Reactor Protection System

  7. An Interactive Computer-Based Circulation System: Design and Development

    Directory of Open Access Journals (Sweden)

    James S. Aagaard

    1972-03-01

    Full Text Available An on-line computer-based circulation control system has been installed at the Northwestern University library. Features of the system include self-service book charge, remote terminal inquiry and update, and automatic production of notices for call-ins and books available. Fine notices are also prepared daily and overdue notices weekly. Important considerations in the design of the system were to minimize costs of operation and to include technical services functions eventually. The system operates on a relatively small computer in a multiprogrammed mode.

  8. Remarkable Computing - the Challenge of Designing for the Home

    DEFF Research Database (Denmark)

    Petersen, Marianne Graves

    2004-01-01

    The vision of ubiquitous computing is floating into the domain of the household, despite arguments that lessons from design of workplace artefacts cannot be blindly transferred into the domain of the household. This paper discusses why the ideal of unremarkable or ubiquitous computing is too narrow...... with respect to the household. It points out how understanding technology use, is a matter of looking into the process of use and on how the specific context of the home, in several ways, call for technology to be remarkable rather than unremarkable....

  9. Design and Evaluation of Chitosan-Based Novel pHSensitive Drug ...

    African Journals Online (AJOL)

    Design and Evaluation of Chitosan-Based Novel pHSensitive Drug Carrier for Sustained ... Scanning electron microscopy(SEM),Raman spectroscopy for particle size analysis. Swelling ratio, Effect of drug loading on encapsulation efficiency

  10. Reforming private drug coverage in Canada: inefficient drug benefit design and the barriers to change in unionized settings.

    Science.gov (United States)

    O'Brady, Sean; Gagnon, Marc-André; Cassels, Alan

    2015-02-01

    Prescription drugs are the highest single cost component for employees' benefits packages in Canada. While industry literature considers cost-containment for prescription drug costs to be a priority for insurers and employers, the implementation of cost-containment measures for private drug plans in Canada remains more of a myth than a reality. Through 18 semi-structured phone interviews conducted with experts from private sector companies, unions, insurers and plan advisors, this study explores the reasons behind this incapacity to implement cost-containment measures by examining how private sector employers negotiate drug benefit design in unionized settings. Respondents were asked questions on how employee benefits are negotiated; the relationships between the players who influence drug benefit design; the role of these players' strategies in influencing plan design; the broad system that underpins drug benefit design; and the potential for a universal pharmacare program in Canada. The study shows that there is consensus about the need to educate employees and employers, more collaboration and data-sharing between these two sets of players, and for external intervention from government to help transform established norms in terms of private drug plan design. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. A Novel Strategy for Mechanism Based Computational Drug Discovery

    Science.gov (United States)

    Subha, Kalyaanamoorthy; Kumar, Gopal Ramesh; Rajalakshmi, Rajasekaran; Aravindhan, Ganesan

    2010-01-01

    Glioma, the common brain tumor, which arises from the glial cells, offers worse prognosis and therapy than any other tumors. Despite the genetic and pathological diversities of malignant gliomas, common signaling pathways that drive cellular proliferation, survival, invasion and angiogenesis have been identified. Very often, various tyrosine kinase receptors are inappropriately activated in human brain tumors and contribute to tumor malignancy. During such tumourous states where multiple pathways are involved, a few of them are responsbile for cell differentiation, proliferation and anti-apoptosis. Computational simulation studies of normal EGFR signaling in glioma together with the mutant EGFR mediated signaling and the MAPK signaling in glioma were carried out. There were no significant cross talks observed between the mutant EGFR and the MAPK pathways and thus from the simulation results, we propose a novel concept of ‘multiple-targeting’ that combines EGFR and Ras targeted therapy thereby providing a better therapeutic value against glioma. Diallyl Disulfide (DADS) that has been commonly used for Ras inhibition in glioma was taken for analyses and the effect of inhibiting the EGFR downstream signaling protein with this DADS was analyzed using the simulation and docking studies. PMID:24179383

  12. A Novel Strategy for Mechanism Based Computational Drug Discovery

    Directory of Open Access Journals (Sweden)

    Kalyaanamoorthy Subha

    2010-01-01

    Full Text Available Glioma, the common brain tumor, which arises from the glial cells, offers worse prognosis and therapy than any other tumors. Despite the genetic and pathological diversities of malignant gliomas, common signaling pathways that drive cellular proliferation, survival, invasion and angiogenesis have been identified. Very often, various tyrosine kinase receptors are inappropriately activated in human brain tumors and contribute to tumor malignancy. During such tumourous states where multiple pathways are involved, a few of them are responsbile for cell differentiation, proliferation and anti-apoptosis. Computational simulation studies of normal EGFR signaling in glioma together with the mutant EGFR mediated signaling and the MAPK signaling in glioma were carried out. There were no significant cross talks observed between the mutant EGFR and the MAPK pathways and thus from the simulation results, we propose a novel concept of ‘multiple-targeting’ that combines EGFR and Ras targeted therapy thereby providing a better therapeutic value against glioma. Diallyl Disulfide (DADS that has been commonly used for Ras inhibition in glioma was taken for analyses and the effect of inhibiting the EGFR downstream signaling protein with this DADS was analyzed using the simulation and docking studies.

  13. 5th International Conference on Design Computing and Cognition

    CERN Document Server

    2014-01-01

    Design thinking, the label given to the acts of designing, has become a paradigmatic view that has transcended the discipline of design and is now widely used in business and elsewhere. As a consequence there is an increasing interest in design research. This is because of the realization that design is part of the wealth creation of a nation and needs to be better understood and taught. The continuing globalization of industry and trade has required nations to re-examine where their core contributions lie if not in production efficiency. Design is a precursor to manufacturing for physical objects and is the precursor to implementation for virtual objects. At the same time, the need for sustainable development requires the design of new products and processes, which feeds a movement towards design innovations and inventions. The papers in this volume are from the Fifth International Conference on Design Computing and Cognition (DCC’12) held at Texas A & M University, USA. They represent the state-of-th...

  14. Enhancing Human-Computer Interaction Design Education: Teaching Affordance Design for Emerging Mobile Devices

    Science.gov (United States)

    Faiola, Anthony; Matei, Sorin Adam

    2010-01-01

    The evolution of human-computer interaction design (HCID) over the last 20 years suggests that there is a growing need for educational scholars to consider new and more applicable theoretical models of interactive product design. The authors suggest that such paradigms would call for an approach that would equip HCID students with a better…

  15. Balancing Expression and Structure in Game Design: Developing Computational Participation Using Studio-Based Design Pedagogy

    Science.gov (United States)

    DeVane, Ben; Steward, Cody; Tran, Kelly M.

    2016-01-01

    This article reports on a project that used a game-creation tool to introduce middle-school students ages 10 to 13 to problem-solving strategies similar to those in computer science through the lens of studio-based design arts. Drawing on historic paradigms in design pedagogy and contemporary educational approaches in the digital arts to teach…

  16. Computational methods in metabolic engineering for strain design.

    Science.gov (United States)

    Long, Matthew R; Ong, Wai Kit; Reed, Jennifer L

    2015-08-01

    Metabolic engineering uses genetic approaches to control microbial metabolism to produce desired compounds. Computational tools can identify new biological routes to chemicals and the changes needed in host metabolism to improve chemical production. Recent computational efforts have focused on exploring what compounds can be made biologically using native, heterologous, and/or enzymes with broad specificity. Additionally, computational methods have been developed to suggest different types of genetic modifications (e.g. gene deletion/addition or up/down regulation), as well as suggest strategies meeting different criteria (e.g. high yield, high productivity, or substrate co-utilization). Strategies to improve the runtime performances have also been developed, which allow for more complex metabolic engineering strategies to be identified. Future incorporation of kinetic considerations will further improve strain design algorithms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Computational modeling of drug-resistant bacteria. Final report

    International Nuclear Information System (INIS)

    2015-01-01

    Initial proposal summary: The evolution of antibiotic-resistant mutants among bacteria (superbugs) is a persistent and growing threat to public health. In many ways, we are engaged in a war with these microorganisms, where the corresponding arms race involves chemical weapons and biological targets. Just as advances in microelectronics, imaging technology and feature recognition software have turned conventional munitions into smart bombs, the long-term objectives of this proposal are to develop highly effective antibiotics using next-generation biomolecular modeling capabilities in tandem with novel subatomic feature detection software. Using model compounds and targets, our design methodology will be validated with correspondingly ultra-high resolution structure-determination methods at premier DOE facilities (single-crystal X-ray diffraction at Argonne National Laboratory, and neutron diffraction at Oak Ridge National Laboratory). The objectives and accomplishments are summarized.

  18. Computational modeling of drug-resistant bacteria. Final report

    Energy Technology Data Exchange (ETDEWEB)

    MacDougall, Preston [Middle Tennessee State Univ., Murfreesboro, TN (United States)

    2015-03-12

    Initial proposal summary: The evolution of antibiotic-resistant mutants among bacteria (superbugs) is a persistent and growing threat to public health. In many ways, we are engaged in a war with these microorganisms, where the corresponding arms race involves chemical weapons and biological targets. Just as advances in microelectronics, imaging technology and feature recognition software have turned conventional munitions into smart bombs, the long-term objectives of this proposal are to develop highly effective antibiotics using next-generation biomolecular modeling capabilities in tandem with novel subatomic feature detection software. Using model compounds and targets, our design methodology will be validated with correspondingly ultra-high resolution structure-determination methods at premier DOE facilities (single-crystal X-ray diffraction at Argonne National Laboratory, and neutron diffraction at Oak Ridge National Laboratory). The objectives and accomplishments are summarized.

  19. Molecular dynamics in drug design: new generations of compstatin analogs.

    Science.gov (United States)

    Tamamis, Phanourios; López de Victoria, Aliana; Gorham, Ronald D; Bellows-Peterson, Meghan L; Pierou, Panayiota; Floudas, Christodoulos A; Morikis, Dimitrios; Archontis, Georgios

    2012-05-01

    We report the computational and rational design of new generations of potential peptide-based inhibitors of the complement protein C3 from the compstatin family. The binding efficacy of the peptides is tested by extensive molecular dynamics-based structural and physicochemical analysis, using 32 atomic detail trajectories in explicit water for 22 peptides bound to human, rat or mouse target protein C3, with a total of 257 ns. The criteria for the new design are: (i) optimization for C3 affinity and for the balance between hydrophobicity and polarity to improve solubility compared to known compstatin analogs; and (ii) development of dual specificity, human-rat/mouse C3 inhibitors, which could be used in animal disease models. Three of the new analogs are analyzed in more detail as they possess strong and novel binding characteristics and are promising candidates for further optimization. This work paves the way for the development of an improved therapeutic for age-related macular degeneration, and other complement system-mediated diseases, compared to known compstatin variants. © 2012 John Wiley & Sons A/S.

  20. Cardioplegia heat exchanger design modelling using computational fluid dynamics.

    Science.gov (United States)

    van Driel, M R

    2000-11-01

    A new cardioplegia heat exchanger has been developed by Sorin Biomedica. A three-dimensional computer-aided design (CAD) model was optimized using computational fluid dynamics (CFD) modelling. CFD optimization techniques have commonly been applied to velocity flow field analysis, but CFD analysis was also used in this study to predict the heat exchange performance of the design before prototype fabrication. The iterative results of the optimization and the actual heat exchange performance of the final configuration are presented in this paper. Based on the behaviour of this model, both the water and blood fluid flow paths of the heat exchanger were optimized. The simulation predicted superior heat exchange performance using an optimal amount of energy exchange surface area, reducing the total contact surface area, the device priming volume and the material costs. Experimental results confirm the empirical results predicted by the CFD analysis.

  1. A conceptual gamma shield design using the DRP model computation

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, E E [Reactor Department, Nuclear Research Center, Atomic Energy Authority, Cairo (Egypt); Rahman, F A [National Center of Nuclear Safety and Radiation Control, Atomic Energy Authority, Cairo (Egypt)

    1997-12-31

    The purpose of this investigation is to assess basic areas of concern in the development of reactor shielding conceptual design calculations. A spherical shield model composed of low carbon steel and lead have been constructed to surround a Co-60 gamma point source. two alternative configurations have been considered in the model computation. The numerical calculations have been performed using both the ANISN code and DRP model computation together with the DLC 75-Bugle 80 data library. A resume of results for deep penetration in different shield materials with different packing densities is presented and analysed. The results showed that the gamma fluxes attenuation is increased with increasing distribution the packing density of the shield material which reflects its importance of considering it as a safety parameter in shielding design. 3 figs.

  2. Soft computing in design and manufacturing of advanced materials

    Science.gov (United States)

    Cios, Krzysztof J.; Baaklini, George Y; Vary, Alex

    1993-01-01

    The potential of fuzzy sets and neural networks, often referred to as soft computing, for aiding in all aspects of manufacturing of advanced materials like ceramics is addressed. In design and manufacturing of advanced materials, it is desirable to find which of the many processing variables contribute most to the desired properties of the material. There is also interest in real time quality control of parameters that govern material properties during processing stages. The concepts of fuzzy sets and neural networks are briefly introduced and it is shown how they can be used in the design and manufacturing processes. These two computational methods are alternatives to other methods such as the Taguchi method. The two methods are demonstrated by using data collected at NASA Lewis Research Center. Future research directions are also discussed.

  3. Computational Methods for Modeling Aptamers and Designing Riboswitches

    Directory of Open Access Journals (Sweden)

    Sha Gong

    2017-11-01

    Full Text Available Riboswitches, which are located within certain noncoding RNA region perform functions as genetic “switches”, regulating when and where genes are expressed in response to certain ligands. Understanding the numerous functions of riboswitches requires computation models to predict structures and structural changes of the aptamer domains. Although aptamers often form a complex structure, computational approaches, such as RNAComposer and Rosetta, have already been applied to model the tertiary (three-dimensional (3D structure for several aptamers. As structural changes in aptamers must be achieved within the certain time window for effective regulation, kinetics is another key point for understanding aptamer function in riboswitch-mediated gene regulation. The coarse-grained self-organized polymer (SOP model using Langevin dynamics simulation has been successfully developed to investigate folding kinetics of aptamers, while their co-transcriptional folding kinetics can be modeled by the helix-based computational method and BarMap approach. Based on the known aptamers, the web server Riboswitch Calculator and other theoretical methods provide a new tool to design synthetic riboswitches. This review will represent an overview of these computational methods for modeling structure and kinetics of riboswitch aptamers and for designing riboswitches.

  4. Semiconductor-inspired design principles for superconducting quantum computing.

    Science.gov (United States)

    Shim, Yun-Pil; Tahan, Charles

    2016-03-17

    Superconducting circuits offer tremendous design flexibility in the quantum regime culminating most recently in the demonstration of few qubit systems supposedly approaching the threshold for fault-tolerant quantum information processing. Competition in the solid-state comes from semiconductor qubits, where nature has bestowed some very useful properties which can be utilized for spin qubit-based quantum computing. Here we begin to explore how selective design principles deduced from spin-based systems could be used to advance superconducting qubit science. We take an initial step along this path proposing an encoded qubit approach realizable with state-of-the-art tunable Josephson junction qubits. Our results show that this design philosophy holds promise, enables microwave-free control, and offers a pathway to future qubit designs with new capabilities such as with higher fidelity or, perhaps, operation at higher temperature. The approach is also especially suited to qubits on the basis of variable super-semi junctions.

  5. Computer- Aided Design in Power Engineering Application of Software Tools

    CERN Document Server

    Stojkovic, Zlatan

    2012-01-01

    This textbooks demonstrates the application of software tools in solving a series of problems from the field of designing power system structures and systems. It contains four chapters: The first chapter leads the reader through all the phases necessary in the procedures of computer aided modeling and simulation. It guides through the complex problems presenting on the basis of eleven original examples. The second chapter presents  application of software tools in power system calculations of power systems equipment design. Several design example calculations are carried out using engineering standards like MATLAB, EMTP/ATP, Excel & Access, AutoCAD and Simulink. The third chapters focuses on the graphical documentation using a collection of software tools (AutoCAD, EPLAN, SIMARIS SIVACON, SIMARIS DESIGN) which enable the complete automation of the development of graphical documentation of a power systems. In the fourth chapter, the application of software tools in the project management in power systems ...

  6. Computer organization and design the hardware/software interface

    CERN Document Server

    Patterson, David A

    2011-01-01

    This Fourth Revised Edition of Computer Organization and Design includes a complete set of updated and new exercises, along with improvements and changes suggested by instructors and students. Focusing on the revolutionary change taking place in industry today--the switch from uniprocessor to multicore microprocessors--this classic textbook has a modern and up-to-date focus on parallelism in all its forms. Examples highlighting multicore and GPU processor designs are supported with performance and benchmarking data. As with previous editions, a MIPS processor is the core used to pres

  7. Computer-aided design of new metal binders

    International Nuclear Information System (INIS)

    Varnek, A.; Fourches, D.; Klimchuk, O.; Marcou, G.; Kireeva, N.; Tsivadze, A.; Solov'ev, V.

    2008-01-01

    Chemoinformatics approaches open new opportunities for computer-aided design of new efficient metal binders. Here, we demonstrate performances of ISIDA and COMET software tools to predict stability constants (log K) of the metal ion/organic ligand complexes in solution and to design in silico new molecules possessing desirable properties. The predictive models for log K of lanthanides complexation in water have been developed. Some new uranyl binders based on monoamides and on phosphoryl-containing podands were suggested theoretically, then synthesized and tested experimentally. Reasonable agreement between experimental uranyl distribution coefficients and theoretically predicted values has been observed. (orig.)

  8. INFORMATION DISPLAY: CONSIDERATIONS FOR DESIGNING COMPUTER-BASED DISPLAY SYSTEMS

    International Nuclear Information System (INIS)

    O'HARA, J.M.; PIRUS, D.; BELTRATCCHI, L.

    2004-01-01

    This paper discussed the presentation of information in computer-based control rooms. Issues associated with the typical displays currently in use are discussed. It is concluded that these displays should be augmented with new displays designed to better meet the information needs of plant personnel and to minimize the need for interface management tasks (the activities personnel have to do to access and organize the information they need). Several approaches to information design are discussed, specifically addressing: (1) monitoring, detection, and situation assessment; (2) routine task performance; and (3) teamwork, crew coordination, collaborative work

  9. Computer based approach to fatigue analysis and design

    International Nuclear Information System (INIS)

    Comstock, T.R.; Bernard, T.; Nieb, J.

    1979-01-01

    An approach is presented which uses a mini-computer based system for data acquisition, analysis and graphic displays relative to fatigue life estimation and design. Procedures are developed for identifying an eliminating damaging events due to overall duty cycle, forced vibration and structural dynamic characteristics. Two case histories, weld failures in heavy vehicles and low cycle fan blade failures, are discussed to illustrate the overall approach. (orig.) 891 RW/orig. 892 RKD [de

  10. Spatial ability in computer-aided design courses

    OpenAIRE

    Torner Ribé, Jordi; Alpiste Penalba, Francesc; Brigos Hermida, Miguel Ángel

    2014-01-01

    Many studies have demonstrated that spatial ability is an important factor in the study of Industrial Engineering. Spatial ability is fundamentally important to the work of an engineer, as it is vital for project design. Among other elements, spatial ability correlates with factors such as good academic results and a natural ability to learn how to use I.T systems and computer programs. Furthermore, the new framework drawn up by the European Higher Education Area (EHEA) guides us as to the...

  11. Neural Network Design on the SRC-6 Reconfigurable Computer

    Science.gov (United States)

    2006-12-01

    fingerprint identification. In this field, automatic identification methods are used to save time, especially for the purpose of fingerprint matching in...grid widths and lengths and therefore was useful in producing an accurate canvas with which to create sample training images. The added benefit of...tools available free of charge and readily accessible on the computer, it was simple to design bitmap data files visually on a canvas and then

  12. Modeling electric fields in two dimensions using computer aided design

    International Nuclear Information System (INIS)

    Gilmore, D.W.; Giovanetti, D.

    1992-01-01

    The authors describe a method for analyzing static electric fields in two dimensions using AutoCAD. The algorithm is coded in LISP and is modeled after Coloumb's Law. The software platform allows for facile graphical manipulations of field renderings and supports a wide range of hardcopy-output and data-storage formats. More generally, this application is representative of the ability to analyze data that is the solution to known mathematical functions with computer aided design (CAD)

  13. CADRIGS--computer aided design reliability interactive graphics system

    International Nuclear Information System (INIS)

    Kwik, R.J.; Polizzi, L.M.; Sticco, S.; Gerrard, P.B.; Yeater, M.L.; Hockenbury, R.W.; Phillips, M.A.

    1982-01-01

    An integrated reliability analysis program combining graphic representation of fault trees, automated data base loadings and reference, and automated construction of reliability code input files was developed. The functional specifications for CADRIGS, the computer aided design reliability interactive graphics system, are presented. Previously developed fault tree segments used in auxiliary feedwater system safety analysis were constructed on CADRIGS and, when combined, yielded results identical to those resulting from manual input to the same reliability codes

  14. Three-dimensional computer aided design system for plant layout

    International Nuclear Information System (INIS)

    Yoshinaga, Toshiaki; Kiguchi, Takashi; Tokumasu, Shinji; Kumamoto, Kenjiro.

    1986-01-01

    The CAD system for three-dimensional plant layout planning, with which the layout of pipings, cable trays, air conditioning ducts and so on in nuclear power plants can be planned and designed effectively in a short period is reported. This system comprises the automatic routing system by storing the rich experience and know-how of designers in a computer as the knowledge, and deciding the layout automatically following the predetermined sequence by using these, the interactive layout system for reviewing the routing results from higher level and modifying to the optimum layout, the layout evaluation system for synthetically evaluating the layout from the viewpoint of the operability such as checkup and maintenance, and the data base system which enables these effective planning and design. In this report, the total constitution of this system and the technical features and effects of the individual subsystems are outlined. In this CAD system for three-dimensional plant layout planning, knowledge engineering, CAD/CAM, computer graphics and other latest technology were introduced, accordingly by applying this system to plant design, the design can be performed quickly, various case studies can be carried out at planning stage, and systematic and optimum layout planning becomes possible. (Kako, I.)

  15. Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases.

    Science.gov (United States)

    Sarafianos, Stefan G; Das, Kalyan; Hughes, Stephen H; Arnold, Eddy

    2004-12-01

    HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites.

  16. The ways and means of fragment-based drug design.

    Science.gov (United States)

    Doak, Bradley C; Norton, Raymond S; Scanlon, Martin J

    2016-11-01

    Fragment-based drug design (FBDD) has emerged as a mainstream approach for the rapid and efficient identification of building blocks that can be used to develop high-affinity ligands against protein targets. One of the strengths of FBDD is the relative ease and low cost of the primary screen to identify fragments that bind. However, the fragments that emerge from primary screens often have low affinities, with K D values in the high μM to mM range, and a significant challenge for FBDD is to develop the initial fragments into more potent ligands. Successful fragment elaboration often requires co-structures of the fragments bound to their target proteins, as well as a range of biophysical and biochemical assays to track potency and efficacy. These challenges have led to the development of specific chemical strategies for the elaboration of weakly-binding fragments into more potent "hits" and lead compounds. In this article we review different approaches that have been employed to meet these challenges and describe some of the strategies that have resulted in several fragment-derived compounds entering clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Peptide-based proteasome inhibitors in anticancer drug design.

    Science.gov (United States)

    Micale, Nicola; Scarbaci, Kety; Troiano, Valeria; Ettari, Roberta; Grasso, Silvana; Zappalà, Maria

    2014-09-01

    The identification of the key role of the eukaryotic 26S proteasome in regulated intracellular proteolysis and its importance as a target in many pathological conditions wherein the proteasomal activity is defective (e.g., malignancies, autoimmune diseases, neurodegenerative diseases, etc.) prompted several research groups to the development of specific inhibitors of this multicatalytic complex with the aim of obtaining valid drug candidates. In regard to the anticancer therapy, the peptide boronate bortezomib (Velcade®) represents the first molecule approved by FDA for the treatment of multiple myeloma in 2003 and mantle cell lymphoma in 2006. Since then, a plethora of molecules targeting the proteasome have been identified as potential anticancer agents and a few of them reached clinical trials or are already in the market (i.e., carfilzomib; Kyprolis®). In most cases, the design of new proteasome inhibitors (PIs) takes into account a proven peptide or pseudopeptide motif as a base structure and places other chemical entities throughout the peptide skeleton in such a way to create an efficacious network of interactions within the catalytic sites. The purpose of this review is to provide an in-depth look at the current state of the research in the field of peptide-based PIs, specifically those ones that might find an application as anticancer agents. © 2014 Wiley Periodicals, Inc.

  18. High-performance computing in accelerating structure design and analysis

    International Nuclear Information System (INIS)

    Li Zenghai; Folwell, Nathan; Ge Lixin; Guetz, Adam; Ivanov, Valentin; Kowalski, Marc; Lee, Lie-Quan; Ng, Cho-Kuen; Schussman, Greg; Stingelin, Lukas; Uplenchwar, Ravindra; Wolf, Michael; Xiao, Liling; Ko, Kwok

    2006-01-01

    Future high-energy accelerators such as the Next Linear Collider (NLC) will accelerate multi-bunch beams of high current and low emittance to obtain high luminosity, which put stringent requirements on the accelerating structures for efficiency and beam stability. While numerical modeling has been quite standard in accelerator R and D, designing the NLC accelerating structure required a new simulation capability because of the geometric complexity and level of accuracy involved. Under the US DOE Advanced Computing initiatives (first the Grand Challenge and now SciDAC), SLAC has developed a suite of electromagnetic codes based on unstructured grids and utilizing high-performance computing to provide an advanced tool for modeling structures at accuracies and scales previously not possible. This paper will discuss the code development and computational science research (e.g. domain decomposition, scalable eigensolvers, adaptive mesh refinement) that have enabled the large-scale simulations needed for meeting the computational challenges posed by the NLC as well as projects such as the PEP-II and RIA. Numerical results will be presented to show how high-performance computing has made a qualitative improvement in accelerator structure modeling for these accelerators, either at the component level (single cell optimization), or on the scale of an entire structure (beam heating and long-range wakefields)

  19. Hardware synthesis from DDL. [Digital Design Language for computer aided design and test of LSI

    Science.gov (United States)

    Shah, A. M.; Shiva, S. G.

    1981-01-01

    The details of the digital systems can be conveniently input into the design automation system by means of Hardware Description Languages (HDL). The Computer Aided Design and Test (CADAT) system at NASA MSFC is used for the LSI design. The Digital Design Language (DDL) has been selected as HDL for the CADAT System. DDL translator output can be used for the hardware implementation of the digital design. This paper addresses problems of selecting the standard cells from the CADAT standard cell library to realize the logic implied by the DDL description of the system.

  20. Application of computer assisted combinatorial chemistry in antivirial, antimalarial and anticancer agents design

    Science.gov (United States)

    Burello, E.; Bologa, C.; Frecer, V.; Miertus, S.

    Combinatorial chemistry and technologies have been developed to a stage where synthetic schemes are available for generation of a large variety of organic molecules. The innovative concept of combinatorial design assumes that screening of a large and diverse library of compounds will increase the probability of finding an active analogue among the compounds tested. Since the rate at which libraries are screened for activity currently constitutes a limitation to the use of combinatorial technologies, it is important to be selective about the number of compounds to be synthesized. Early experience with combinatorial chemistry indicated that chemical diversity alone did not result in a significant increase in the number of generated lead compounds. Emphasis has therefore been increasingly put on the use of computer assisted combinatorial chemical techniques. Computational methods are valuable in the design of virtual libraries of molecular models. Selection strategies based on computed physicochemical properties of the models or of a target compound are introduced to reduce the time and costs of library synthesis and screening. In addition, computational structure-based library focusing methods can be used to perform in silico screening of the activity of compounds against a target receptor by docking the ligands into the receptor model. Three case studies are discussed dealing with the design of targeted combinatorial libraries of inhibitors of HIV-1 protease, P. falciparum plasmepsin and human urokinase as potential antivirial, antimalarial and anticancer drugs. These illustrate library focusing strategies.

  1. Current therapeutic molecules and targets in neurodegenerative diseases based on in silico drug design.

    Science.gov (United States)

    Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem

    2018-03-15

    As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Aiding Design of Wave Energy Converters via Computational Simulations

    Science.gov (United States)

    Jebeli Aqdam, Hejar; Ahmadi, Babak; Raessi, Mehdi; Tootkaboni, Mazdak

    2015-11-01

    With the increasing interest in renewable energy sources, wave energy converters will continue to gain attention as a viable alternative to current electricity production methods. It is therefore crucial to develop computational tools for the design and analysis of wave energy converters. A successful design requires balance between the design performance and cost. Here an analytical solution is used for the approximate analysis of interactions between a flap-type wave energy converter (WEC) and waves. The method is verified using other flow solvers and experimental test cases. Then the model is used in conjunction with a powerful heuristic optimization engine, Charged System Search (CSS) to explore the WEC design space. CSS is inspired by charged particles behavior. It searches the design space by considering candidate answers as charged particles and moving them based on the Coulomb's laws of electrostatics and Newton's laws of motion to find the global optimum. Finally the impacts of changes in different design parameters on the power takeout of the superior WEC designs are investigated. National Science Foundation, CBET-1236462.

  3. Predicting the usefulness of therapeutic drug monitoring of mycophenolic acid: a computer simulation

    NARCIS (Netherlands)

    van Hest, Reinier; Mathot, Ron; Vulto, Arnold; Weimar, Willem; van Gelder, Teun

    2005-01-01

    The usefulness of therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) was investigated with a computer simulation model. For a fixed-dose (FD) and a concentration-controlled (CC) MMF dosing regimen exposure to mycophenolic acid (MPA) was compared. A nonlinear mixed-effects model

  4. Computational Analysis of Single Nucleotide Polymorphisms Associated with Altered Drug Responsiveness in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Valerio Costa

    2016-06-01

    Full Text Available Type 2 diabetes (T2D is one of the most frequent mortality causes in western countries, with rapidly increasing prevalence. Anti-diabetic drugs are the first therapeutic approach, although many patients develop drug resistance. Most drug responsiveness variability can be explained by genetic causes. Inter-individual variability is principally due to single nucleotide polymorphisms, and differential drug responsiveness has been correlated to alteration in genes involved in drug metabolism (CYP2C9 or insulin signaling (IRS1, ABCC8, KCNJ11 and PPARG. However, most genome-wide association studies did not provide clues about the contribution of DNA variations to impaired drug responsiveness. Thus, characterizing T2D drug responsiveness variants is needed to guide clinicians toward tailored therapeutic approaches. Here, we extensively investigated polymorphisms associated with altered drug response in T2D, predicting their effects in silico. Combining different computational approaches, we focused on the expression pattern of genes correlated to drug resistance and inferred evolutionary conservation of polymorphic residues, computationally predicting the biochemical properties of polymorphic proteins. Using RNA-Sequencing followed by targeted validation, we identified and experimentally confirmed that two nucleotide variations in the CAPN10 gene—currently annotated as intronic—fall within two new transcripts in this locus. Additionally, we found that a Single Nucleotide Polymorphism (SNP, currently reported as intergenic, maps to the intron of a new transcript, harboring CAPN10 and GPR35 genes, which undergoes non-sense mediated decay. Finally, we analyzed variants that fall into non-coding regulatory regions of yet underestimated functional significance, predicting that some of them can potentially affect gene expression and/or post-transcriptional regulation of mRNAs affecting the splicing.

  5. Paediatric Drug Development and Formulation Design-a European Perspective

    NARCIS (Netherlands)

    Nales, D.A.; Kozarewicz, Piotr; Aylward, Brian; de Vries, Rutger; Egberts, Toine C G; Rademaker, Carin M A; Schobben, Alfred F A M

    The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed

  6. Design and Development of a Proniosomal Transdermal Drug ...

    African Journals Online (AJOL)

    Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...

  7. Protein-Protein Docking in Drug Design and Discovery.

    Science.gov (United States)

    Kaczor, Agnieszka A; Bartuzi, Damian; Stępniewski, Tomasz Maciej; Matosiuk, Dariusz; Selent, Jana

    2018-01-01

    Protein-protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called "hot spots" in protein-protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein-protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein-protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein-protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein-protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein-protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein-protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

  8. Computer aided design of piping for a radiochemical plant

    Energy Technology Data Exchange (ETDEWEB)

    Selvaraj, P G; Chandrasekhar, A; Chandrasekar, A V [Reprocessing Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India); Raju, R P; Mahudeeswaran, K V; Kumar, S V [Reprocessing Group, Bhabha Atomic Research Centre, Mumbai (India)

    1994-06-01

    In a radiochemical plant such as reprocessing plants, process equipment, storage tanks, liquid transfer systems and the associated pipe lines etc. are housed in series of concrete cells. Availability of limited cell space/volume, provision of various modes of liquid transfers with associated redundancies and instrumentation lines with standby alternatives increase the overall piping density. Designing such high density piping layout without interference is quite complex and needs lot of human efforts. This paper briefly describes development of computer codes for the entire scheme of design, drafting and fabrication of piping for nuclear fuel reprocessing plant. The general organisation of various programs, their functions, the complete sequence of the scheme and the flow of data are presented. High degree of reliability of each routine, considerable error checking facilities, marking legends on the drawings, provision for scaling in drafting and accuracy to the extent of one mm in layout design are some of the important features of this scheme. (author). 1 fig.

  9. Computer aided fixture design - A case based approach

    Science.gov (United States)

    Tanji, Shekhar; Raiker, Saiesh; Mathew, Arun Tom

    2017-11-01

    Automated fixture design plays important role in process planning and integration of CAD and CAM. An automated fixture setup design system is developed where when fixturing surfaces and points are described allowing modular fixture components to get automatically select for generating fixture units and placed into position with satisfying assembled conditions. In past, various knowledge based system have been developed to implement CAFD in practice. In this paper, to obtain an acceptable automated machining fixture design, a case-based reasoning method with developed retrieval system is proposed. Visual Basic (VB) programming language is used in integrating with SolidWorks API (Application programming interface) module for better retrieval procedure reducing computational time. These properties are incorporated in numerical simulation to determine the best fit for practical use.

  10. Inhibitors of HIV-protease from computational design. A history of theory and synthesis still to be fully appreciated.

    Science.gov (United States)

    Berti, Federico; Frecer, Vladimir; Miertus, Stanislav

    2014-01-01

    Despite the fact that HIV-Protease is an over 20 years old target, computational approaches to rational design of its inhibitors still have a great potential to stimulate the synthesis of new compounds and the discovery of new, potent derivatives, ever capable to overcome the problem of drug resistance. This review deals with successful examples of inhibitors identified by computational approaches, rather than by knowledge-based design. Such methodologies include the development of energy and scoring functions, docking protocols, statistical models, virtual combinatorial chemistry. Computations addressing drug resistance, and the development of related models as the substrate envelope hypothesis are also reviewed. In some cases, the identified structures required the development of synthetic approaches in order to obtain the desired target molecules; several examples are reported.

  11. The synergistic use of computation, chemistry and biology to discover novel peptide-based drugs: the time is right.

    Science.gov (United States)

    Audie, J; Boyd, C

    2010-01-01

    The case for peptide-based drugs is compelling. Due to their chemical, physical and conformational diversity, and relatively unproblematic toxicity and immunogenicity, peptides represent excellent starting material for drug discovery. Nature has solved many physiological and pharmacological problems through the use of peptides, polypeptides and proteins. If nature could solve such a diversity of challenging biological problems through the use of peptides, it seems reasonable to infer that human ingenuity will prove even more successful. And this, indeed, appears to be the case, as a number of scientific and methodological advances are making peptides and peptide-based compounds ever more promising pharmacological agents. Chief among these advances are powerful chemical and biological screening technologies for lead identification and optimization, methods for enhancing peptide in vivo stability, bioavailability and cell-permeability, and new delivery technologies. Other advances include the development and experimental validation of robust computational methods for peptide lead identification and optimization. Finally, scientific analysis, biology and chemistry indicate the prospect of designing relatively small peptides to therapeutically modulate so-called 'undruggable' protein-protein interactions. Taken together a clear picture is emerging: through the synergistic use of the scientific imagination and the computational, chemical and biological methods that are currently available, effective peptide therapeutics for novel targets can be designed that surpass even the proven peptidic designs of nature.

  12. Design Of Computer Based Test Using The Unified Modeling Language

    Science.gov (United States)

    Tedyyana, Agus; Danuri; Lidyawati

    2017-12-01

    The Admission selection of Politeknik Negeri Bengkalis through interest and talent search (PMDK), Joint Selection of admission test for state Polytechnics (SB-UMPN) and Independent (UM-Polbeng) were conducted by using paper-based Test (PBT). Paper Based Test model has some weaknesses. They are wasting too much paper, the leaking of the questios to the public, and data manipulation of the test result. This reasearch was Aimed to create a Computer-based Test (CBT) models by using Unified Modeling Language (UML) the which consists of Use Case diagrams, Activity diagram and sequence diagrams. During the designing process of the application, it is important to pay attention on the process of giving the password for the test questions before they were shown through encryption and description process. RSA cryptography algorithm was used in this process. Then, the questions shown in the questions banks were randomized by using the Fisher-Yates Shuffle method. The network architecture used in Computer Based test application was a client-server network models and Local Area Network (LAN). The result of the design was the Computer Based Test application for admission to the selection of Politeknik Negeri Bengkalis.

  13. 77 FR 74195 - Draft Guidance for Industry and Food and Drug Administration Staff; Design Considerations for...

    Science.gov (United States)

    2012-12-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1161] Draft Guidance for Industry and Food and Drug Administration Staff; Design Considerations for Devices Intended for Home Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

  14. Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design

    Science.gov (United States)

    Ishikawa, Toshihisa; Tamura, Ai; Saito, Hikaru; Wakabayashi, Kanako; Nakagawa, Hiroshi

    2005-10-01

    In the post-genome-sequencing era, emerging genomic technologies are shifting the paradigm for drug discovery and development. Nevertheless, drug discovery and development still remain high-risk and high-stakes ventures with long and costly timelines. Indeed, the attrition of drug candidates in preclinical and development stages is a major problem in drug design. For at least 30% of the candidates, this attrition is due to poor pharmacokinetics and toxicity. Thus, pharmaceutical companies have begun to seriously re-evaluate their current strategies of drug discovery and development. In that light, we propose that a transport mechanism-based design might help to create new, pharmacokinetically advantageous drugs, and as such should be considered an important component of drug design strategy. Performing enzyme- and/or cell-based drug transporter, interaction tests may greatly facilitate drug development and allow the prediction of drug-drug interactions. We recently developed methods for high-speed functional screening and quantitative structure-activity relationship analysis to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide a practical tool to screen synthetic and natural compounds, and these data can be applied to the molecular design of new drugs. In this review article, we present an overview on the genetic polymorphisms of human ABC transporter ABCG2 and new camptothecin analogues that can circumvent AGCG2-associated multidrug resistance of cancer.

  15. 21 CFR 516.36 - Insufficient quantities of MUMS-designated drugs.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.36 Insufficient quantities of... the 7-year period of exclusive marketing rights. (b) If, within the time that FDA specifies, the...

  16. Hypothesis driven drug design: improving quality and effectiveness of the design-make-test-analyse cycle.

    Science.gov (United States)

    Plowright, Alleyn T; Johnstone, Craig; Kihlberg, Jan; Pettersson, Jonas; Robb, Graeme; Thompson, Richard A

    2012-01-01

    In drug discovery, the central process of constructing and testing hypotheses, carefully conducting experiments and analysing the associated data for new findings and information is known as the design-make-test-analyse cycle. Each step relies heavily on the inputs and outputs of the other three components. In this article we report our efforts to improve and integrate all parts to enable smooth and rapid flow of high quality ideas. Key improvements include enhancing multi-disciplinary input into 'Design', increasing the use of knowledge and reducing cycle times in 'Make', providing parallel sets of relevant data within ten working days in 'Test' and maximising the learning in 'Analyse'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Software Infrastructure for Computer-aided Drug Discovery and Development, a Practical Example with Guidelines.

    Science.gov (United States)

    Moretti, Loris; Sartori, Luca

    2016-09-01

    In the field of Computer-Aided Drug Discovery and Development (CADDD) the proper software infrastructure is essential for everyday investigations. The creation of such an environment should be carefully planned and implemented with certain features in order to be productive and efficient. Here we describe a solution to integrate standard computational services into a functional unit that empowers modelling applications for drug discovery. This system allows users with various level of expertise to run in silico experiments automatically and without the burden of file formatting for different software, managing the actual computation, keeping track of the activities and graphical rendering of the structural outcomes. To showcase the potential of this approach, performances of five different docking programs on an Hiv-1 protease test set are presented. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Designing a hands-on brain computer interface laboratory course.

    Science.gov (United States)

    Khalighinejad, Bahar; Long, Laura Kathleen; Mesgarani, Nima

    2016-08-01

    Devices and systems that interact with the brain have become a growing field of research and development in recent years. Engineering students are well positioned to contribute to both hardware development and signal analysis techniques in this field. However, this area has been left out of most engineering curricula. We developed an electroencephalography (EEG) based brain computer interface (BCI) laboratory course to educate students through hands-on experiments. The course is offered jointly by the Biomedical Engineering, Electrical Engineering, and Computer Science Departments of Columbia University in the City of New York and is open to senior undergraduate and graduate students. The course provides an effective introduction to the experimental design, neuroscience concepts, data analysis techniques, and technical skills required in the field of BCI.

  19. From experiment to design -- Fault characterization and detection in parallel computer systems using computational accelerators

    Science.gov (United States)

    Yim, Keun Soo

    This dissertation summarizes experimental validation and co-design studies conducted to optimize the fault detection capabilities and overheads in hybrid computer systems (e.g., using CPUs and Graphics Processing Units, or GPUs), and consequently to improve the scalability of parallel computer systems using computational accelerators. The experimental validation studies were conducted to help us understand the failure characteristics of CPU-GPU hybrid computer systems under various types of hardware faults. The main characterization targets were faults that are difficult to detect and/or recover from, e.g., faults that cause long latency failures (Ch. 3), faults in dynamically allocated resources (Ch. 4), faults in GPUs (Ch. 5), faults in MPI programs (Ch. 6), and microarchitecture-level faults with specific timing features (Ch. 7). The co-design studies were based on the characterization results. One of the co-designed systems has a set of source-to-source translators that customize and strategically place error detectors in the source code of target GPU programs (Ch. 5). Another co-designed system uses an extension card to learn the normal behavioral and semantic execution patterns of message-passing processes executing on CPUs, and to detect abnormal behaviors of those parallel processes (Ch. 6). The third co-designed system is a co-processor that has a set of new instructions in order to support software-implemented fault detection techniques (Ch. 7). The work described in this dissertation gains more importance because heterogeneous processors have become an essential component of state-of-the-art supercomputers. GPUs were used in three of the five fastest supercomputers that were operating in 2011. Our work included comprehensive fault characterization studies in CPU-GPU hybrid computers. In CPUs, we monitored the target systems for a long period of time after injecting faults (a temporally comprehensive experiment), and injected faults into various types of

  20. Computational design of mould sprue for injection moulding thermoplastics

    Directory of Open Access Journals (Sweden)

    Muralidhar Lakkanna

    2016-01-01

    Full Text Available To injection mould polymers, designing mould is a key task involving several critical decisions with direct implications to yield quality, productivity and frugality. One prominent decision among them is specifying sprue-bush conduit expansion as it significantly influences overall injection moulding; abstruseness anguish in its design criteria deceives direct determination. Intuitively designers decide it wisely and then exasperate by optimising or manipulating processing parameters. To overwhelm that anomaly this research aims at proposing an ideal design criteria holistically for all polymeric materials also tend as a functional assessment metric towards perfection i.e., criteria to specify sprue conduit size before mould development. Accordingly, a priori analytical criterion was deduced quantitatively as expansion ratio from ubiquitous empirical relationships specifically a.k.a an exclusive expansion angle imperatively configured for injectant properties. Its computational intelligence advantage was leveraged to augment functionality of perfectly injecting into an impression gap, while synchronising both injector capacity and desired moulding features. For comprehensiveness, it was continuously sensitised over infinite scale as an explicit factor dependent on in-situ spatio-temporal injectant state perplexity with discrete slope and altitude for each polymeric character. In which congregant ranges of apparent viscosity and shear thinning index were conceived to characteristically assort most thermoplastics. Thereon results accorded aggressive conduit expansion widening for viscous incrust, while a very aggressive narrowing for shear thinning encrust; among them apparent viscosity had relative dominance. This important rationale would certainly form a priori design basis as well diagnose filling issues causing several defects. Like this the proposed generic design criteria, being simple would immensely benefit mould designers besides serve

  1. Identification of novel Mycobacterium tuberculosis dihydrofolate reductase inhibitors through rational drug design

    Directory of Open Access Journals (Sweden)

    Mymoona Akhter

    2016-01-01

    Conclusion: Structure based drug design can be used as an effective tool for the design of new cheiocal entity. Number of novel agents have been identified as antitubercular agents whose mechanism of action needs to be ascertained.

  2. Malavefes: A computational voice-enabled malaria fuzzy informatics software for correct dosage prescription of anti-malarial drugs

    Directory of Open Access Journals (Sweden)

    Olugbenga O. Oluwagbemi

    2018-04-01

    Full Text Available Malaria is one of the infectious diseases consistently inherent in many Sub-Sahara African countries. Among the issues of concern are the consequences of wrong diagnosis and dosage administration of anti-malarial drugs on sick patients; these have resulted into various degrees of complications ranging from severe headaches, stomach and body discomfort, blurred vision, dizziness, hallucinations, and in extreme cases, death. Many expert systems have been developed to support different infectious disease diagnoses, but not sure of any yet, that have been specifically designed as a voice-based application to diagnose and translate malaria patients’ symptomatic data for pre-laboratory screening and correct prescription of proper dosage of the appropriate medication. We developed Malavefes, (a malaria voice-enabled computational fuzzy expert system for correct dosage prescription of anti-malarial drugs using Visual Basic.NET., and Java programming languages. Data collation for this research was conducted by survey from existing literature and interview from public health experts. The database for this malaria drug informatics system was implemented using Microsoft Access. The Root Sum Square (RSS was implemented as the inference engine of Malavefes to make inferences from rules, while Centre of Gravity (CoG was implemented as the defuzzification engine. The drug recommendation module was voice-enabled. Additional anti-malaria drug expiration validation software was developed using Java programming language. We conducted a user-evaluation of the performance and user-experience of the Malavefes software. Keywords: Informatics, Bioinformatics, Fuzzy, Anti-malaria, Voice computing, Dosage prescription

  3. Design of Probabilistic Random Forests with Applications to Anticancer Drug Sensitivity Prediction.

    Science.gov (United States)

    Rahman, Raziur; Haider, Saad; Ghosh, Souparno; Pal, Ranadip

    2015-01-01

    Random forests consisting of an ensemble of regression trees with equal weights are frequently used for design of predictive models. In this article, we consider an extension of the methodology by representing the regression trees in the form of probabilistic trees and analyzing the nature of heteroscedasticity. The probabilistic tree representation allows for analytical computation of confidence intervals (CIs), and the tree weight optimization is expected to provide stricter CIs with comparable performance in mean error. We approached the ensemble of probabilistic trees' prediction from the perspectives of a mixture distribution and as a weighted sum of correlated random variables. We applied our methodology to the drug sensitivity prediction problem on synthetic and cancer cell line encyclopedia dataset and illustrated that tree weights can be selected to reduce the average length of the CI without increase in mean error.

  4. Computational Tools and Algorithms for Designing Customized Synthetic Genes

    Directory of Open Access Journals (Sweden)

    Nathan eGould

    2014-10-01

    Full Text Available Advances in DNA synthesis have enabled the construction of artificial genes, gene circuits, and genomes of bacterial scale. Freedom in de-novo design of synthetic constructs provides significant power in studying the impact of mutations in sequence features, and verifying hypotheses on the functional information that is encoded in nucleic and amino acids. To aid this goal, a large number of software tools of variable sophistication have been implemented, enabling the design of synthetic genes for sequence optimization based on rationally defined properties. The first generation of tools dealt predominantly with singular objectives such as codon usage optimization and unique restriction site incorporation. Recent years have seen the emergence of sequence design tools that aim to evolve sequences toward combinations of objectives. The design of optimal protein coding sequences adhering to multiple objectives is computationally hard, and most tools rely on heuristics to sample the vast sequence design space. In this review we study some of the algorithmic issues behind gene optimization and the approaches that different tools have adopted to redesign genes and optimize desired coding features. We utilize test cases to demonstrate the efficiency of each approach, as well as identify their strengths and limitations.

  5. Computational Tools and Algorithms for Designing Customized Synthetic Genes

    Energy Technology Data Exchange (ETDEWEB)

    Gould, Nathan [Department of Computer Science, The College of New Jersey, Ewing, NJ (United States); Hendy, Oliver [Department of Biology, The College of New Jersey, Ewing, NJ (United States); Papamichail, Dimitris, E-mail: papamicd@tcnj.edu [Department of Computer Science, The College of New Jersey, Ewing, NJ (United States)

    2014-10-06

    Advances in DNA synthesis have enabled the construction of artificial genes, gene circuits, and genomes of bacterial scale. Freedom in de novo design of synthetic constructs provides significant power in studying the impact of mutations in sequence features, and verifying hypotheses on the functional information that is encoded in nucleic and amino acids. To aid this goal, a large number of software tools of variable sophistication have been implemented, enabling the design of synthetic genes for sequence optimization based on rationally defined properties. The first generation of tools dealt predominantly with singular objectives such as codon usage optimization and unique restriction site incorporation. Recent years have seen the emergence of sequence design tools that aim to evolve sequences toward combinations of objectives. The design of optimal protein-coding sequences adhering to multiple objectives is computationally hard, and most tools rely on heuristics to sample the vast sequence design space. In this review, we study some of the algorithmic issues behind gene optimization and the approaches that different tools have adopted to redesign genes and optimize desired coding features. We utilize test cases to demonstrate the efficiency of each approach, as well as identify their strengths and limitations.

  6. Computational Tools and Algorithms for Designing Customized Synthetic Genes

    International Nuclear Information System (INIS)

    Gould, Nathan; Hendy, Oliver; Papamichail, Dimitris

    2014-01-01

    Advances in DNA synthesis have enabled the construction of artificial genes, gene circuits, and genomes of bacterial scale. Freedom in de novo design of synthetic constructs provides significant power in studying the impact of mutations in sequence features, and verifying hypotheses on the functional information that is encoded in nucleic and amino acids. To aid this goal, a large number of software tools of variable sophistication have been implemented, enabling the design of synthetic genes for sequence optimization based on rationally defined properties. The first generation of tools dealt predominantly with singular objectives such as codon usage optimization and unique restriction site incorporation. Recent years have seen the emergence of sequence design tools that aim to evolve sequences toward combinations of objectives. The design of optimal protein-coding sequences adhering to multiple objectives is computationally hard, and most tools rely on heuristics to sample the vast sequence design space. In this review, we study some of the algorithmic issues behind gene optimization and the approaches that different tools have adopted to redesign genes and optimize desired coding features. We utilize test cases to demonstrate the efficiency of each approach, as well as identify their strengths and limitations.

  7. Computer-aided design of bromelain and papain covalent immobilization

    OpenAIRE

    Bessy Cutiño-Avila; Dayrom Gil Pradas; Carlos Aragón Abreu; Yuniel Fernández Marrero; Martha Hernández de la Torre; Emir Salas Sarduy; María de los Ángeles Chávez Planes; José Manuel Guisán Seijas; Joaquín Díaz Brito; Alberto del Monte-Martínez

    2014-01-01

    Título en español: Diseño asistido por computadora de la inmovilización covalente de bromelina y papaína. Título corto: Computer-aided design of bromelain and papain.  Abstract: Enzymes as immobilized derivatives have been widely used in Food, Agrochemical, Pharmaceutical and Biotechnological industries. Protein immobilization is probably the most used technology to improve the operational stability of these molecules. Bromelain (Ananas comosus) and papain (Carica papaya) are cystein pr...

  8. Fisher information in the design of computer simulation experiments

    Energy Technology Data Exchange (ETDEWEB)

    StehlIk, Milan; Mueller, Werner G [Department of Applied Statistics, Johannes-Kepler-University Linz Freistaedter Strasse 315, A-4040 Linz (Austria)], E-mail: Milan.Stehlik@jku.at, E-mail: Werner.Mueller@jku.at

    2008-11-01

    The concept of Fisher information is conveniently used as a basis for designing efficient experiments. However, if the output stems from computer simulations they are often approximated as realizations of correlated random fields. Consequently, the conditions under which Fisher information may be suitable must be restated. In the paper we intend to give some simple but illuminating examples for these cases. 'Random phenomena have increasing importance in Engineering and Physics, therefore theoretical results are strongly needed. But there is a gap between the probability theory used by mathematicians and practitioners. Two very different languages have been generated in this way...' (Paul Kree, Paris 1995)

  9. Fisher information in the design of computer simulation experiments

    International Nuclear Information System (INIS)

    StehlIk, Milan; Mueller, Werner G

    2008-01-01

    The concept of Fisher information is conveniently used as a basis for designing efficient experiments. However, if the output stems from computer simulations they are often approximated as realizations of correlated random fields. Consequently, the conditions under which Fisher information may be suitable must be restated. In the paper we intend to give some simple but illuminating examples for these cases. 'Random phenomena have increasing importance in Engineering and Physics, therefore theoretical results are strongly needed. But there is a gap between the probability theory used by mathematicians and practitioners. Two very different languages have been generated in this way...' (Paul Kree, Paris 1995)

  10. Efficient Use of Preisach Hysteresis Model in Computer Aided Design

    Directory of Open Access Journals (Sweden)

    IONITA, V.

    2013-05-01

    Full Text Available The paper presents a practical detailed analysis regarding the use of the classical Preisach hysteresis model, covering all the steps, from measuring the necessary data for the model identification to the implementation in a software code for Computer Aided Design (CAD in Electrical Engineering. An efficient numerical method is proposed and the hysteresis modeling accuracy is tested on magnetic recording materials. The procedure includes the correction of the experimental data, which are used for the hysteresis model identification, taking into account the demagnetizing effect for the sample that is measured in an open-circuit device (a vibrating sample magnetometer.

  11. Design of Carborane Molecular Architectures via Electronic Structure Computations

    International Nuclear Information System (INIS)

    Oliva, J.M.; Serrano-Andres, L.; Klein, D.J.; Schleyer, P.V.R.; Mich, J.

    2009-01-01

    Quantum-mechanical electronic structure computations were employed to explore initial steps towards a comprehensive design of poly carborane architectures through assembly of molecular units. Aspects considered were (i) the striking modification of geometrical parameters through substitution, (ii) endohedral carboranes and proposed ejection mechanisms for energy/ion/atom/energy storage/transport, (iii) the excited state character in single and dimeric molecular units, and (iv) higher architectural constructs. A goal of this work is to find optimal architectures where atom/ion/energy/spin transport within carborane superclusters is feasible in order to modernize and improve future photo energy processes.

  12. Membrane Transporters: Structure, Function and Targets for Drug Design

    Science.gov (United States)

    Ravna, Aina W.; Sager, Georg; Dahl, Svein G.; Sylte, Ingebrigt

    Current therapeutic drugs act on four main types of molecular targets: enzymes, receptors, ion channels and transporters, among which a major part (60-70%) are membrane proteins. This review discusses the molecular structures and potential impact of membrane transporter proteins on new drug discovery. The three-dimensional (3D) molecular structure of a protein contains information about the active site and possible ligand binding, and about evolutionary relationships within the protein family. Transporters have a recognition site for a particular substrate, which may be used as a target for drugs inhibiting the transporter or acting as a false substrate. Three groups of transporters have particular interest as drug targets: the major facilitator superfamily, which includes almost 4000 different proteins transporting sugars, polyols, drugs, neurotransmitters, metabolites, amino acids, peptides, organic and inorganic anions and many other substrates; the ATP-binding cassette superfamily, which plays an important role in multidrug resistance in cancer chemotherapy; and the neurotransmitter:sodium symporter family, which includes the molecular targets for some of the most widely used psychotropic drugs. Recent technical advances have increased the number of known 3D structures of membrane transporters, and demonstrated that they form a divergent group of proteins with large conformational flexibility which facilitates transport of the substrate.

  13. Design of Novel Ophthalmic Formulation Containing Drug Nanoparticles and Its Usefulness as Anti-glaucoma Drugs.

    Science.gov (United States)

    Nagai, Noriaki

    2016-01-01

    The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles. For a more concrete example, a mean particle size of disulfiram (DSF) treated with bead mill is 183 nm. The corneal penetration and corneal residence time of DSF from the ophthalmic dispersion containing DSF nanoparticles were significantly higher than those from a 2-hydroxypropyl-β-cyclodextrin solution containing DSF (DSF solution). It is known that the administration of DSF has intraocular pressure (IOP)-reducing effects. The IOP-reducing effects of the ophthalmic dispersion containing DSF nanoparticles were significantly greater than those of the DSF solution in rabbits (the IOP was enhanced by placing the rabbits in a dark room for 5 h). In addition, the ophthalmic dispersion containing DSF nanoparticles is better tolerated by corneal epithelial cells than DSF solution. It is possible that dispersions containing DSF nanoparticles provide new possibilities for effectively treating glaucoma, and that ocular drug delivery systems using drug nanoparticles may expand their usage for therapy in the ophthalmologic field.

  14. Analysis of Drug Design for a Selection of G Protein-Coupled Neuro-Receptors Using Neural Network Techniques

    DEFF Research Database (Denmark)

    Agerskov, Claus; Mortensen, Rasmus M.; Bohr, Henrik G.

    2015-01-01

    A study is presented on how well possible drug-molecules can be predicted with respect to their function and binding to a selection of neuro-receptors by the use of artificial neural networks. The ligands investigated in this study are chosen to be corresponding to the G protein-coupled receptors...... computational tools, able to aid in drug-design in a fast and cheap fashion, compared to conventional pharmacological techniques....... mu-opioid, serotonin 2B (5-HT2B) and metabotropic glutamate D5. They are selected due to the availability of pharmacological drug-molecule binding data for these receptors. Feedback and deep belief artificial neural network architectures (NNs) were chosen to perform the task of aiding drug-design.......925. The performance of 8 category networks (8 output classes for binding strength) obtained a prediction accuracy of above 60 %. After training the networks, tests were done on how well the systems could be used as an aid in designing candidate drug molecules. Specifically, it was shown how a selection of chemical...

  15. Exploring G Protein-Coupled Receptors (GPCRs) Ligand Space via Cheminformatics Approaches: Impact on Rational Drug Design

    Science.gov (United States)

    Basith, Shaherin; Cui, Minghua; Macalino, Stephani J. Y.; Park, Jongmi; Clavio, Nina A. B.; Kang, Soosung; Choi, Sun

    2018-01-01

    The primary goal of rational drug discovery is the identification of selective ligands which act on single or multiple drug targets to achieve the desired clinical outcome through the exploration of total chemical space. To identify such desired compounds, computational approaches are necessary in predicting their drug-like properties. G Protein-Coupled Receptors (GPCRs) represent one of the largest and most important integral membrane protein families. These receptors serve as increasingly attractive drug targets due to their relevance in the treatment of various diseases, such as inflammatory disorders, metabolic imbalances, cardiac disorders, cancer, monogenic disorders, etc. In the last decade, multitudes of three-dimensional (3D) structures were solved for diverse GPCRs, thus referring to this period as the “golden age for GPCR structural biology.” Moreover, accumulation of data about the chemical properties of GPCR ligands has garnered much interest toward the exploration of GPCR chemical space. Due to the steady increase in the structural, ligand, and functional data of GPCRs, several cheminformatics approaches have been implemented in its drug discovery pipeline. In this review, we mainly focus on the cheminformatics-based paradigms in GPCR drug discovery. We provide a comprehensive view on the ligand– and structure-based cheminformatics approaches which are best illustrated via GPCR case studies. Furthermore, an appropriate combination of ligand-based knowledge with structure-based ones, i.e., integrated approach, which is emerging as a promising strategy for cheminformatics-based GPCR drug design is also discussed. PMID:29593527

  16. Quantum mechanics implementation in drug-design workflows: does it really help? [Corrigendum

    Directory of Open Access Journals (Sweden)

    Arodola OA

    2017-11-01

    Full Text Available Arodola OA, Soliman MES. Quantum mechanics implementation in drug-design workflows: does it really help? Drug Design, Development and Therapy. 2017;11:2551–2564.Figure 3 on page 2557 contains errors. The correct figure is shown.Read the original article

  17. Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

    Science.gov (United States)

    Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

    2010-01-01

    A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

  18. A role for fragment-based drug design in developing novel lead compounds for central nervous system targets

    Directory of Open Access Journals (Sweden)

    Michael J. Wasko

    2015-09-01

    Full Text Available Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacologic screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening, which employs computer models of the target protein to narrow the search for possible leads. A variant of virtual screening is fragment-based drug design, an emerging in silico lead discovery method that introduces low molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for growing the lead candidate. Current efforts in virtual fragment-based drug design within central nervous system (CNS targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor binding pocket using the fragment as a scaffold. This process places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

  19. THE METHOD OF DESIGNING ASSISTED ON COMPUTER OF THE

    Directory of Open Access Journals (Sweden)

    LUCA Cornelia

    2015-05-01

    Full Text Available To the base of the footwear soles designing, is the shoe last. The shoe lasts have irregular shapes, with various curves witch can’t be represented by a simple mathematic function. In order to design the footwear’s soles it’s necessary to take from the shoe last some base contours. These contours are obtained with high precision in a 3D CAD system. In the paper, it will be presented a method of designing of the soles for footwear, computer assisted. The copying process of the shoe last is done using the 3D digitizer. For digitizing, the shoe last spatial shape is positioned on the peripheral of data gathering, witch follows automatically the shoe last’s surface. The wire network obtained through digitizing is numerically interpolated with the interpolator functions in order to obtain the spatial numerical shape of the shoe last. The 3D designing of the sole will be realized on the numerical shape of the shoe last following the next steps: the manufacture of the sole’s surface, the lateral surface realization of the sole’s shape, obtaining the link surface between the lateral side and the planner one of the sole, of the sole’s margin, the sole’s designing contains the skid proof area. The main advantage of the designing method is the design precision, visualization in 3D space of the sole and the possibility to take the best decision viewing the acceptance of new sole’s pattern.

  20. Rapid Sampling of Hydrogen Bond Networks for Computational Protein Design.

    Science.gov (United States)

    Maguire, Jack B; Boyken, Scott E; Baker, David; Kuhlman, Brian

    2018-05-08

    Hydrogen bond networks play a critical role in determining the stability and specificity of biomolecular complexes, and the ability to design such networks is important for engineering novel structures, interactions, and enzymes. One key feature of hydrogen bond networks that makes them difficult to rationally engineer is that they are highly cooperative and are not energetically favorable until the hydrogen bonding potential has been satisfied for all buried polar groups in the network. Existing computational methods for protein design are ill-equipped for creating these highly cooperative networks because they rely on energy functions and sampling strategies that are focused on pairwise interactions. To enable the design of complex hydrogen bond networks, we have developed a new sampling protocol in the molecular modeling program Rosetta that explicitly searches for sets of amino acid mutations that can form self-contained hydrogen bond networks. For a given set of designable residues, the protocol often identifies many alternative sets of mutations/networks, and we show that it can readily be applied to large sets of residues at protein-protein interfaces or in the interior of proteins. The protocol builds on a recently developed method in Rosetta for designing hydrogen bond networks that has been experimentally validated for small symmetric systems but was not extensible to many larger protein structures and complexes. The sampling protocol we describe here not only recapitulates previously validated designs with performance improvements but also yields viable hydrogen bond networks for cases where the previous method fails, such as the design of large, asymmetric interfaces relevant to engineering protein-based therapeutics.