Computational methods in drug discovery.

PubMed

Leelananda, Sumudu P; Lindert, Steffen

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 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.

A Simple and Resource-efficient Setup for the Computer-aided Drug Design Laboratory.

PubMed

Moretti, Loris; Sartori, Luca

2016-10-01

Undertaking modelling investigations for Computer-Aided Drug Design (CADD) requires a proper environment. In principle, this could be done on a single computer, but the reality of a drug discovery program requires robustness and high-throughput computing (HTC) to efficiently support the research. Therefore, a more capable alternative is needed but its implementation has no widespread solution. Here, the realization of such a computing facility is discussed, from general layout to technical details all aspects are covered. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computer-Aided Drug Discovery Approaches against the Tropical Infectious Diseases Malaria, Tuberculosis, Trypanosomiasis, and Leishmaniasis.

PubMed

Njogu, Peter M; Guantai, Eric M; Pavadai, Elumalai; Chibale, Kelly

2016-01-08

Despite the tremendous improvement in overall global health heralded by the adoption of the Millennium Declaration in the year 2000, tropical infections remain a major health problem in the developing world. Recent estimates indicate that the major tropical infectious diseases, namely, malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for more than 2.2 million deaths and a loss of approximately 85 million disability-adjusted life years annually. The crucial role of chemotherapy in curtailing the deleterious health and economic impacts of these infections has invigorated the search for new drugs against tropical infectious diseases. The research efforts have involved increased application of computational technologies in mainstream drug discovery programs at the hit identification, hit-to-lead, and lead optimization stages. This review highlights various computer-aided drug discovery approaches that have been utilized in efforts to identify novel antimalarial, antitubercular, antitrypanosomal, and antileishmanial agents. The focus is largely on developments over the past 5 years (2010-2014).

Computing elastic anisotropy to discover gum-metal-like structural alloys

NASA Astrophysics Data System (ADS)

Winter, I. S.; de Jong, M.; Asta, M.; Chrzan, D. C.

2017-08-01

The computer aided discovery of structural alloys is a burgeoning but still challenging area of research. A primary challenge in the field is to identify computable screening parameters that embody key structural alloy properties. Here, an elastic anisotropy parameter that captures a material's susceptibility to solute solution strengthening is identified. The parameter has many applications in the discovery and optimization of structural materials. As a first example, the parameter is used to identify alloys that might display the super elasticity, super strength, and high ductility of the class of TiNb alloys known as gum metals. In addition, it is noted that the parameter can be used to screen candidate alloys for shape memory response, and potentially aid in the optimization of the mechanical properties of high-entropy alloys.

Computer-Aided Experiment Planning toward Causal Discovery in Neuroscience.

PubMed

Matiasz, Nicholas J; Wood, Justin; Wang, Wei; Silva, Alcino J; Hsu, William

2017-01-01

Computers help neuroscientists to analyze experimental results by automating the application of statistics; however, computer-aided experiment planning is far less common, due to a lack of similar quantitative formalisms for systematically assessing evidence and uncertainty. While ontologies and other Semantic Web resources help neuroscientists to assimilate required domain knowledge, experiment planning requires not only ontological but also epistemological (e.g., methodological) information regarding how knowledge was obtained. Here, we outline how epistemological principles and graphical representations of causality can be used to formalize experiment planning toward causal discovery. We outline two complementary approaches to experiment planning: one that quantifies evidence per the principles of convergence and consistency, and another that quantifies uncertainty using logical representations of constraints on causal structure. These approaches operationalize experiment planning as the search for an experiment that either maximizes evidence or minimizes uncertainty. Despite work in laboratory automation, humans must still plan experiments and will likely continue to do so for some time. There is thus a great need for experiment-planning frameworks that are not only amenable to machine computation but also useful as aids in human reasoning.

Computer-aided drug design at Boehringer Ingelheim

NASA Astrophysics Data System (ADS)

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.

Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors.

PubMed

Frett, Brendan; McConnell, Nick; Smith, Catherine C; Wang, Yuanxiang; Shah, Neil P; Li, Hong-yu

2015-04-13

The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Computer aided drug design

NASA Astrophysics Data System (ADS)

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.

Innovative computer-aided methods for the discovery of new kinase ligands.

PubMed

Abuhammad, Areej; Taha, Mutasem

2016-04-01

Recent evidence points to significant roles played by protein kinases in cell signaling and cellular proliferation. Faulty protein kinases are involved in cancer, diabetes and chronic inflammation. Efforts are continuously carried out to discover new inhibitors for selected protein kinases. In this review, we discuss two new computer-aided methodologies we developed to mine virtual databases for new bioactive compounds. One method is ligand-based exploration of the pharmacophoric space of inhibitors of any particular biotarget followed by quantitative structure-activity relationship-based selection of the best pharmacophore(s). The second approach is structure-based assuming that potent ligands come into contact with binding site spots distinct from those contacted by weakly potent ligands. Both approaches yield pharmacophores useful as 3D search queries for the discovery of new bioactive (kinase) inhibitors.

Hit discovery and hit-to-lead approaches.

PubMed

Keseru, György M; Makara, Gergely M

2006-08-01

Hit discovery technologies range from traditional high-throughput screening to affinity selection of large libraries, fragment-based techniques and computer-aided de novo design, many of which have been extensively reviewed. Development of quality leads using hit confirmation and hit-to-lead approaches present their own challenges, depending on the hit discovery method used to identify the initial hits. In this paper, we summarize common industry practices adopted to tackle hit-to-lead challenges and review how the advantages and drawbacks of different hit discovery techniques could affect the various issues hit-to-lead groups face.

Gibbs Free Energy of Hydrolytic Water Molecule in Acyl-Enzyme Intermediates of a Serine Protease: A Potential Application for Computer-Aided Discovery of Mechanism-Based Reversible Covalent Inhibitors.

PubMed

Masuda, Yosuke; Yamaotsu, Noriyuki; Hirono, Shuichi

2017-01-01

In order to predict the potencies of mechanism-based reversible covalent inhibitors, the relationships between calculated Gibbs free energy of hydrolytic water molecule in acyl-trypsin intermediates and experimentally measured catalytic rate constants (k cat ) were investigated. After obtaining representative solution structures by molecular dynamics (MD) simulations, hydration thermodynamics analyses using WaterMap™ were conducted. Consequently, we found for the first time that when Gibbs free energy of the hydrolytic water molecule was lower, logarithms of k cat were also lower. The hydrolytic water molecule with favorable Gibbs free energy may hydrolyze acylated serine slowly. Gibbs free energy of hydrolytic water molecule might be a useful descriptor for computer-aided discovery of mechanism-based reversible covalent inhibitors of hydrolytic enzymes.

Computer-aided discovery of a metal-organic framework with superior oxygen uptake.

PubMed

Moghadam, Peyman Z; Islamoglu, Timur; Goswami, Subhadip; Exley, Jason; Fantham, Marcus; Kaminski, Clemens F; Snurr, Randall Q; Farha, Omar K; Fairen-Jimenez, David

2018-04-11

Current advances in materials science have resulted in the rapid emergence of thousands of functional adsorbent materials in recent years. This clearly creates multiple opportunities for their potential application, but it also creates the following challenge: how does one identify the most promising structures, among the thousands of possibilities, for a particular application? Here, we present a case of computer-aided material discovery, in which we complete the full cycle from computational screening of metal-organic framework materials for oxygen storage, to identification, synthesis and measurement of oxygen adsorption in the top-ranked structure. We introduce an interactive visualization concept to analyze over 1000 unique structure-property plots in five dimensions and delimit the relationships between structural properties and oxygen adsorption performance at different pressures for 2932 already-synthesized structures. We also report a world-record holding material for oxygen storage, UMCM-152, which delivers 22.5% more oxygen than the best known material to date, to the best of our knowledge.

Tools, techniques, organisation and culture of the CADD group at Sygnature Discovery.

PubMed

St-Gallay, Steve A; Sambrook-Smith, Colin P

2017-03-01

Computer-aided drug design encompasses a wide variety of tools and techniques, and can be implemented with a range of organisational structures and focus in different organisations. Here we outline the computational chemistry skills within Sygnature Discovery, along with the software and hardware at our disposal, and briefly discuss the methods that are not employed and why. The goal of the group is to provide support for design and analysis in order to improve the quality of compounds synthesised and reduce the timelines of drug discovery projects, and we reveal how this is achieved at Sygnature. Impact on medicinal chemistry is vital to demonstrating the value of computational chemistry, and we discuss the approaches taken to influence the list of compounds for synthesis, and how we recognise success. Finally we touch on some of the areas being developed within the team in order to provide further value to the projects and clients.

Tools, techniques, organisation and culture of the CADD group at Sygnature Discovery

NASA Astrophysics Data System (ADS)

St-Gallay, Steve A.; Sambrook-Smith, Colin P.

2017-03-01

Computer-aided drug design encompasses a wide variety of tools and techniques, and can be implemented with a range of organisational structures and focus in different organisations. Here we outline the computational chemistry skills within Sygnature Discovery, along with the software and hardware at our disposal, and briefly discuss the methods that are not employed and why. The goal of the group is to provide support for design and analysis in order to improve the quality of compounds synthesised and reduce the timelines of drug discovery projects, and we reveal how this is achieved at Sygnature. Impact on medicinal chemistry is vital to demonstrating the value of computational chemistry, and we discuss the approaches taken to influence the list of compounds for synthesis, and how we recognise success. Finally we touch on some of the areas being developed within the team in order to provide further value to the projects and clients.

Medicine's Life Inside the Body

MedlinePlus

... Science > A Medicine's Life Inside the Body Inside Life Science View All Articles | Inside Life Science Home Page A Medicine's Life Inside the Body ... Medicines Work Computation Aids Drug Discovery This Inside Life Science article also appears on LiveScience . Learn about related ...

Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.

PubMed

Kruziki, Max A; Sarma, Vidur; Hackel, Benjamin J

2018-06-05

Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. We systematically constructed eight libraries and comparatively evaluated their efficacy for binder discovery via yeast display against a panel of targets. Conservation of a cysteine pair at the termini of the first diversified paratope loop increased binder discovery 16-fold ( p < 0.001). Yet two other libraries with conserved cysteine pairs, within the second loop or an interloop pair, did not aid discovery thereby indicating site-specific impact. Via a yeast display protease resistance assay, Gp2 variants from the loop one cysteine pair library were 3.3 ± 2.1-fold ( p = 0.005) more stable than nonconstrained variants. Sitewise constraint of noncysteine residues-guided by previously evolved binders, natural Gp2 homology, computed stability, and structural analysis-did not aid discovery. A panel of binders to programmed death ligand 1 (PD-L1), a key target in cancer immunotherapy, were discovered from the loop 1 cysteine constraint library. Affinity maturation via loop walking resulted in strong, specific cellular PD-L1 affinity ( K d = 6-9 nM).

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

PubMed

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.

Problem-Solving Models for Computer Literacy: Getting Smarter at Solving Problems. Student Lessons.

ERIC Educational Resources Information Center

Moursund, David

This book is intended for use as a student guide. It is about human problem solving and provides information on how the mind works, placing a major emphasis on the role of computers as an aid in problem solving. The book is written with the underlying philosophy of discovery-based learning based on two premises: first, through the appropriate…

Ab Initio Reactive Computer Aided Molecular Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martínez, Todd J.

Few would dispute that theoretical chemistry tools can now provide keen insights into chemical phenomena. Yet the holy grail of efficient and reliable prediction of complex reactivity has remained elusive. Fortunately, recent advances in electronic structure theory based on the concepts of both element- and rank-sparsity, coupled with the emergence of new highly parallel computer architectures, have led to a significant increase in the time and length scales which can be simulated using first principles molecular dynamics. This then opens the possibility of new discovery-based approaches to chemical reactivity, such as the recently proposed ab initio nanoreactor. Here, we arguemore » that due to these and other recent advances, the holy grail of computational discovery for complex chemical reactivity is rapidly coming within our reach.« less

Ab Initio Reactive Computer Aided Molecular Design

DOE PAGES

Martínez, Todd J.

2017-03-21

Few would dispute that theoretical chemistry tools can now provide keen insights into chemical phenomena. Yet the holy grail of efficient and reliable prediction of complex reactivity has remained elusive. Fortunately, recent advances in electronic structure theory based on the concepts of both element- and rank-sparsity, coupled with the emergence of new highly parallel computer architectures, have led to a significant increase in the time and length scales which can be simulated using first principles molecular dynamics. This then opens the possibility of new discovery-based approaches to chemical reactivity, such as the recently proposed ab initio nanoreactor. Here, we arguemore » that due to these and other recent advances, the holy grail of computational discovery for complex chemical reactivity is rapidly coming within our reach.« less

Advances in the treatment of explicit water molecules in docking and binding free energy calculations.

PubMed

Hu, Xiao; Maffucci, Irene; Contini, Alessandro

2018-05-13

The inclusion of direct effects mediated by water during the ligand-receptor recognition is a hot-topic of modern computational chemistry applied to drug discovery and development. Docking or virtual screening with explicit hydration is still debatable, despite the successful cases that have been presented in the last years. Indeed, how to select the water molecules that will be included in the docking process or how the included waters should be treated remain open questions. In this review, we will discuss some of the most recent methods that can be used in computational drug discovery and drug development when the effect of a single water, or of a small network of interacting waters, needs to be explicitly considered. Here, we analyse software to aid the selection, or to predict the position, of water molecules that are going to be explicitly considered in later docking studies. We also present software and protocols able to efficiently treat flexible water molecules during docking, including examples of applications. Finally, we discuss methods based on molecular dynamics simulations that can be used to integrate docking studies or to reliably and efficiently compute binding energies of ligands in presence of interfacial or bridging water molecules. Software applications aiding the design of new drugs that exploit water molecules, either as displaceable residues or as bridges to the receptor, are constantly being developed. Although further validation is needed, workflows that explicitly consider water will probably become a standard for computational drug discovery soon. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.

PubMed

Thomford, Nicholas Ekow; Senthebane, Dimakatso Alice; Rowe, Arielle; Munro, Daniella; Seele, Palesa; Maroyi, Alfred; Dzobo, Kevin

2018-05-25

The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of "active compound" has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of 'organ-on chip' and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review discusses plant-based natural product drug discovery and how innovative technologies play a role in next-generation drug discovery.

How to Quickly Import CAD Geometry into Thermal Desktop

NASA Technical Reports Server (NTRS)

Wright, Shonte; Beltran, Emilio

2002-01-01

There are several groups at JPL (Jet Propulsion Laboratory) that are committed to concurrent design efforts, two are featured here. Center for Space Mission Architecture and Design (CSMAD) enables the practical application of advanced process technologies in JPL's mission architecture process. Team I functions as an incubator for projects that are in the Discovery, and even pre-Discovery proposal stages. JPL's concurrent design environment is to a large extent centered on the CAD (Computer Aided Design) file. During concurrent design sessions CAD geometry is ported to other more specialized engineering design packages.

Exploring the Role of Receptor Flexibility in Structure-Based Drug Discovery

PubMed Central

Feixas, Ferran; Lindert, Steffen; Sinko, William; McCammon, J. Andrew

2015-01-01

The proper understanding of biomolecular recognition mechanisms that take place in a drug target is of paramount importance to improve the efficiency of drug discovery and development. The intrinsic dynamic character of proteins has a strong influence on biomolecular recognition mechanisms and models such as conformational selection have been widely used to account for this dynamic association process. However, conformational changes occurring in the receptor prior and upon association with other molecules are diverse and not obvious to predict when only a few structures of the receptor are available. In view of the prominent role of protein flexibility in ligand binding and its implications for drug discovery, it is of great interest to identify receptor conformations that play a major role in biomolecular recognition before starting rational drug design efforts. In this review, we discuss a number of recent advances in computer-aided drug discovery techniques that have been proposed to incorporate receptor flexibility into structure-based drug design. The allowance for receptor flexibility provided by computational techniques such as molecular dynamics simulations or enhanced sampling techniques helps to improve the accuracy of methods used to estimate binding affinities and, thus, such methods can contribute to the discovery of novel drug leads. PMID:24332165

An overview of aldehyde oxidase: an enzyme of emerging importance in novel drug discovery.

PubMed

Rashidi, Mohammad-Reza; Soltani, Somaieh

2017-03-01

Given the rising trend in medicinal chemistry strategy to reduce cytochrome P450-dependent metabolism, aldehyde oxidase (AOX) has recently gained increased attention in drug discovery programs and the number of drug candidates that are metabolized by AOX is steadily growing. Areas covered: Despite the emerging importance of AOX in drug discovery, there are certain major recognized problems associated with AOX-mediated metabolism of drugs. Intra- and inter-species variations in AOX activity, the lack of reliable and predictive animal models using the common experimental animals, and failure in the predictions of in vivo metabolic activity of AOX using traditional in vitro methods are among these issues that are covered in this article. A comprehensive review of computational human AOX (hAOX) related studies are also provided. Expert opinion: Following the recent progress in the stem cell field, the authors recommend the application of organoids technology as an effective tool to solve the fundamental problems associated with the evaluation of AOX in drug discovery. The recent success in resolving the hAOX crystal structure can too be another valuable data source for the study of AOX-catalyzed metabolism of new drug candidates, using computer-aided drug discovery methods.

The impact of pharmacophore modeling in drug design.

PubMed

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.

Towards agile large-scale predictive modelling in drug discovery with flow-based programming design principles.

PubMed

Lampa, Samuel; Alvarsson, Jonathan; Spjuth, Ola

2016-01-01

Predictive modelling in drug discovery is challenging to automate as it often contains multiple analysis steps and might involve cross-validation and parameter tuning that create complex dependencies between tasks. With large-scale data or when using computationally demanding modelling methods, e-infrastructures such as high-performance or cloud computing are required, adding to the existing challenges of fault-tolerant automation. Workflow management systems can aid in many of these challenges, but the currently available systems are lacking in the functionality needed to enable agile and flexible predictive modelling. We here present an approach inspired by elements of the flow-based programming paradigm, implemented as an extension of the Luigi system which we name SciLuigi. We also discuss the experiences from using the approach when modelling a large set of biochemical interactions using a shared computer cluster.Graphical abstract.

Computer-Aided Discovery of Formal Specification Behavioral Requirements and Requirement to Implementation Mappings

DTIC Science & Technology

2014-01-01

the executable SRM is developed according to the specification and marketing documents. Hence, for example, the Vehicles, Car, and Truck classes in...transitions ternary relation: transitions ⊆ states x transitionIDs x states, such as <"Init", "Tr1", " stP "> • A conditions unary relation bound to

Predicting future discoveries from current scientific literature.

PubMed

Petrič, Ingrid; Cestnik, Bojan

2014-01-01

Knowledge discovery in biomedicine is a time-consuming process starting from the basic research, through preclinical testing, towards possible clinical applications. Crossing of conceptual boundaries is often needed for groundbreaking biomedical research that generates highly inventive discoveries. We demonstrate the ability of a creative literature mining method to advance valuable new discoveries based on rare ideas from existing literature. When emerging ideas from scientific literature are put together as fragments of knowledge in a systematic way, they may lead to original, sometimes surprising, research findings. If enough scientific evidence is already published for the association of such findings, they can be considered as scientific hypotheses. In this chapter, we describe a method for the computer-aided generation of such hypotheses based on the existing scientific literature. Our literature-based discovery of NF-kappaB with its possible connections to autism was recently approved by scientific community, which confirms the ability of our literature mining methodology to accelerate future discoveries based on rare ideas from existing literature.

Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands.

PubMed

Rosano, Camillo; Ponassi, Marco; Santolla, Maria Francesca; Pisano, Assunta; Felli, Lamberto; Vivacqua, Adele; Maggiolini, Marcello; Lappano, Rosamaria

2016-01-01

Estrogens influence multiple physiological processes and are implicated in many diseases as well. Cellular responses to estrogens are mainly mediated by the estrogen receptors (ER)α and ERβ, which act as ligand-activated transcription factors. Recently, a member of the G protein-coupled receptor (GPCR) superfamily, namely GPER/GPR30, has been identified as a further mediator of estrogen signalling in different pathophysiological conditions, including cancer. Today, computational methods are commonly used in all areas of health science research. Among these methods, virtual ligand screening has become an established technique for hit discovery and optimization. The absence of an established three-dimensional structure of GPER promoted studies of structure-based drug design in order to build reliable molecular models of this receptor. Here, we discuss the results obtained through the structure-based virtual ligand screening for GPER, which allowed the identification and synthesis of different selective agonist and antagonist moieties. These compounds led significant advances in our understanding of the GPER function at the cellular, tissue, and organismal levels. In particular, selective GPER ligands were critical toward the evaluation of the role elicited by this receptor in several pathophysiological conditions, including cancer. Considering that structure-based approaches are fundamental in drug discovery, future research breakthroughs with the aid of computer-aided molecular design and chemo-bioinformatics could generate a new class of drugs that, acting through GPER, would be useful in a variety of diseases as well as in innovative anticancer strategies.

Computational Design and Discovery of Ni-Based Alloys and Coatings: Thermodynamic Approaches Validated by Experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Zi-Kui; Gleeson, Brian; Shang, Shunli

This project developed computational tools that can complement and support experimental efforts in order to enable discovery and more efficient development of Ni-base structural materials and coatings. The project goal was reached through an integrated computation-predictive and experimental-validation approach, including first-principles calculations, thermodynamic CALPHAD (CALculation of PHAse Diagram), and experimental investigations on compositions relevant to Ni-base superalloys and coatings in terms of oxide layer growth and microstructure stabilities. The developed description included composition ranges typical for coating alloys and, hence, allow for prediction of thermodynamic properties for these material systems. The calculation of phase compositions, phase fraction, and phase stabilities,more » which are directly related to properties such as ductility and strength, was a valuable contribution, along with the collection of computational tools that are required to meet the increasing demands for strong, ductile and environmentally-protective coatings. Specifically, a suitable thermodynamic description for the Ni-Al-Cr-Co-Si-Hf-Y system was developed for bulk alloy and coating compositions. Experiments were performed to validate and refine the thermodynamics from the CALPHAD modeling approach. Additionally, alloys produced using predictions from the current computational models were studied in terms of their oxidation performance. Finally, results obtained from experiments aided in the development of a thermodynamic modeling automation tool called ESPEI/pycalphad - for more rapid discovery and development of new materials.« less

Getting the Most out of PubChem for Virtual Screening

PubMed Central

Kim, Sunghwan

2016-01-01

Introduction With the emergence of the “big data” era, the biomedical research community has great interest in exploiting publicly available chemical information for drug discovery. PubChem is an example of public databases that provide a large amount of chemical information free of charge. Areas covered This article provides an overview of how PubChem’s data, tools, and services can be used for virtual screening and reviews recent publications that discuss important aspects of exploiting PubChem for drug discovery. Expert opinion PubChem offers comprehensive chemical information useful for drug discovery. It also provides multiple programmatic access routes, which are essential to build automated virtual screening pipelines that exploit PubChem data. In addition, PubChemRDF allows users to download PubChem data and load them into a local computing facility, facilitating data integration between PubChem and other resources. PubChem resources have been used in many studies for developing bioactivity and toxicity prediction models, discovering polypharmacologic (multi-target) ligands, and identifying new macromolecule targets of compounds (for drug-repurposing or off-target side effect prediction). These studies demonstrate the usefulness of PubChem as a key resource for computer-aided drug discovery and related area. PMID:27454129

Large-scale high-throughput computer-aided discovery of advanced materials using cloud computing

NASA Astrophysics Data System (ADS)

Bazhirov, Timur; Mohammadi, Mohammad; Ding, Kevin; Barabash, Sergey

Recent advances in cloud computing made it possible to access large-scale computational resources completely on-demand in a rapid and efficient manner. When combined with high fidelity simulations, they serve as an alternative pathway to enable computational discovery and design of new materials through large-scale high-throughput screening. Here, we present a case study for a cloud platform implemented at Exabyte Inc. We perform calculations to screen lightweight ternary alloys for thermodynamic stability. Due to the lack of experimental data for most such systems, we rely on theoretical approaches based on first-principle pseudopotential density functional theory. We calculate the formation energies for a set of ternary compounds approximated by special quasirandom structures. During an example run we were able to scale to 10,656 CPUs within 7 minutes from the start, and obtain results for 296 compounds within 38 hours. The results indicate that the ultimate formation enthalpy of ternary systems can be negative for some of lightweight alloys, including Li and Mg compounds. We conclude that compared to traditional capital-intensive approach that requires in on-premises hardware resources, cloud computing is agile and cost-effective, yet scalable and delivers similar performance.

Comptational Design Of Functional CA-S-H and Oxide Doped Alloy Systems

NASA Astrophysics Data System (ADS)

Yang, Shizhong; Chilla, Lokeshwar; Yang, Yan; Li, Kuo; Wicker, Scott; Zhao, Guang-Lin; Khosravi, Ebrahim; Bai, Shuju; Zhang, Boliang; Guo, Shengmin

Computer aided functional materials design accelerates the discovery of novel materials. This presentation will cover our recent research advance on the Ca-S-H system properties prediction and oxide doped high entropy alloy property simulation and experiment validation. Several recent developed computational materials design methods were utilized to the two systems physical and chemical properties prediction. A comparison of simulation results to the corresponding experiment data will be introduced. This research is partially supported by NSF CIMM project (OIA-15410795 and the Louisiana BoR), NSF HBCU Supplement climate change and ecosystem sustainability subproject 3, and LONI high performance computing time allocation loni mat bio7.

C2 Approaches: Looking for the Sweet Spot

DTIC Science & Technology

2013-06-01

more information) IMAGE (see Lizotte et al., 2008; Lizotte, Bernier, Mokhtari , & Boivin, 2013) was developed as a suite of generic representation...439–446). Fukuoka, Japan. Lizotte, M., Bernier, F., Mokhtari , M., & Boivin, E. (2013). IMAGE Final Report: An Interactive Computer-aided Cognition...Capability for C4ISR Complexity Discovery (No. TR 2013-397). Québec, Canada: Defence R&D Canada - Valcartier. Lizotte, M., Bernier, F., Mokhtari , M

Quantitative structure-activity relationship: promising advances in drug discovery platforms.

PubMed

Wang, Tao; Wu, Mian-Bin; Lin, Jian-Ping; Yang, Li-Rong

2015-12-01

Quantitative structure-activity relationship (QSAR) modeling is one of the most popular computer-aided tools employed in medicinal chemistry for drug discovery and lead optimization. It is especially powerful in the absence of 3D structures of specific drug targets. QSAR methods have been shown to draw public attention since they were first introduced. In this review, the authors provide a brief discussion of the basic principles of QSAR, model development and model validation. They also highlight the current applications of QSAR in different fields, particularly in virtual screening, rational drug design and multi-target QSAR. Finally, in view of recent controversies, the authors detail the challenges faced by QSAR modeling and the relevant solutions. The aim of this review is to show how QSAR modeling can be applied in novel drug discovery, design and lead optimization. QSAR should intentionally be used as a powerful tool for fragment-based drug design platforms in the field of drug discovery and design. Although there have been an increasing number of experimentally determined protein structures in recent years, a great number of protein structures cannot be easily obtained (i.e., membrane transport proteins and G-protein coupled receptors). Fragment-based drug discovery, such as QSAR, could be applied further and have a significant role in dealing with these problems. Moreover, along with the development of computer software and hardware, it is believed that QSAR will be increasingly important.

From laptop to benchtop to bedside: Structure-based Drug Design on Protein Targets

PubMed Central

Chen, Lu; Morrow, John K.; Tran, Hoang T.; Phatak, Sharangdhar S.; Du-Cuny, Lei; Zhang, Shuxing

2013-01-01

As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting protein-ligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues, may also cause failures. In this review, state-of-the-art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches. PMID:22316152

Nonhuman Primate Models and Understanding the Pathogenesis of HIV Infection and AIDS.

PubMed

Veazey, Ronald S; Lackner, Andrew A

2017-12-01

Research using nonhuman primates (NHPs) as models for human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) has resulted in tremendous achievements not only in the prevention and treatment of HIV, but also in biomedical research more broadly. Once considered a death sentence, HIV infection is now fairly well controlled with combination antiretroviral treatments, almost all of which were first tested for efficacy and safety in nonhuman primates or other laboratory animals. Research in NHP has led to "dogma changing" discoveries in immunology, infectious disease, and even our own genetics. We now know that many of our genes are retroviral remnants, or developed in response to archaic HIV-like retroviral infections. Early studies involving blood from HIV patients and in experiments in cultured tissues contributed to confusion regarding the cause of AIDS and impeded progress in the development of effective interventions. Research on the many retroviruses of different NHP species have broadened our understanding of human immunology and perhaps even our origins and evolution as a species. In combination with recent advances in molecular biology and computational analytics, research in NHPs has unique potential for discoveries that will directly lead to new cures for old human and animal diseases, including HIV/AIDS. © The Author 2017. Published by Oxford University Press on behalf of the National Academy of Sciences. All rights reserved. For permissions, please email: journals.permissions@oup.com.

SemaTyP: a knowledge graph based literature mining method for drug discovery.

PubMed

Sang, Shengtian; Yang, Zhihao; Wang, Lei; Liu, Xiaoxia; Lin, Hongfei; Wang, Jian

2018-05-30

Drug discovery is the process through which potential new medicines are identified. High-throughput screening and computer-aided drug discovery/design are the two main drug discovery methods for now, which have successfully discovered a series of drugs. However, development of new drugs is still an extremely time-consuming and expensive process. Biomedical literature contains important clues for the identification of potential treatments. It could support experts in biomedicine on their way towards new discoveries. Here, we propose a biomedical knowledge graph-based drug discovery method called SemaTyP, which discovers candidate drugs for diseases by mining published biomedical literature. We first construct a biomedical knowledge graph with the relations extracted from biomedical abstracts, then a logistic regression model is trained by learning the semantic types of paths of known drug therapies' existing in the biomedical knowledge graph, finally the learned model is used to discover drug therapies for new diseases. The experimental results show that our method could not only effectively discover new drug therapies for new diseases, but also could provide the potential mechanism of action of the candidate drugs. In this paper we propose a novel knowledge graph based literature mining method for drug discovery. It could be a supplementary method for current drug discovery methods.

Harnessing the power of emerging petascale platforms

NASA Astrophysics Data System (ADS)

Mellor-Crummey, John

2007-07-01

As part of the US Department of Energy's Scientific Discovery through Advanced Computing (SciDAC-2) program, science teams are tackling problems that require computational simulation and modeling at the petascale. A grand challenge for computer science is to develop software technology that makes it easier to harness the power of these systems to aid scientific discovery. As part of its activities, the SciDAC-2 Center for Scalable Application Development Software (CScADS) is building open source software tools to support efficient scientific computing on the emerging leadership-class platforms. In this paper, we describe two tools for performance analysis and tuning that are being developed as part of CScADS: a tool for analyzing scalability and performance, and a tool for optimizing loop nests for better node performance. We motivate these tools by showing how they apply to S3D, a turbulent combustion code under development at Sandia National Laboratory. For S3D, our node performance analysis tool helped uncover several performance bottlenecks. Using our loop nest optimization tool, we transformed S3D's most costly loop nest to reduce execution time by a factor of 2.94 for a processor working on a 503 domain.

Parallel Density-Based Clustering for Discovery of Ionospheric Phenomena

NASA Astrophysics Data System (ADS)

Pankratius, V.; Gowanlock, M.; Blair, D. M.

2015-12-01

Ionospheric total electron content maps derived from global networks of dual-frequency GPS receivers can reveal a plethora of ionospheric features in real-time and are key to space weather studies and natural hazard monitoring. However, growing data volumes from expanding sensor networks are making manual exploratory studies challenging. As the community is heading towards Big Data ionospheric science, automation and Computer-Aided Discovery become indispensable tools for scientists. One problem of machine learning methods is that they require domain-specific adaptations in order to be effective and useful for scientists. Addressing this problem, our Computer-Aided Discovery approach allows scientists to express various physical models as well as perturbation ranges for parameters. The search space is explored through an automated system and parallel processing of batched workloads, which finds corresponding matches and similarities in empirical data. We discuss density-based clustering as a particular method we employ in this process. Specifically, we adapt Density-Based Spatial Clustering of Applications with Noise (DBSCAN). This algorithm groups geospatial data points based on density. Clusters of points can be of arbitrary shape, and the number of clusters is not predetermined by the algorithm; only two input parameters need to be specified: (1) a distance threshold, (2) a minimum number of points within that threshold. We discuss an implementation of DBSCAN for batched workloads that is amenable to parallelization on manycore architectures such as Intel's Xeon Phi accelerator with 60+ general-purpose cores. This manycore parallelization can cluster large volumes of ionospheric total electronic content data quickly. Potential applications for cluster detection include the visualization, tracing, and examination of traveling ionospheric disturbances or other propagating phenomena. Acknowledgments. We acknowledge support from NSF ACI-1442997 (PI V. Pankratius).

Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target.

PubMed

Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M Michael; Taguchi, Y-H; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A Mary; Velmurugan, D; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu

2015-11-26

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective.

Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target

PubMed Central

Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M. Michael; Taguchi, Y-h.; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A. Mary; Velmurugan, D.; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu

2015-01-01

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective. PMID:26607293

Computer-Aided Drug Design Methods.

PubMed

Yu, Wenbo; MacKerell, Alexander D

2017-01-01

Computational approaches are useful tools to interpret and guide experiments to expedite the antibiotic drug design process. Structure-based drug design (SBDD) and ligand-based drug design (LBDD) are the two general types of computer-aided drug design (CADD) approaches in existence. SBDD methods analyze macromolecular target 3-dimensional structural information, typically of proteins or RNA, to identify key sites and interactions that are important for their respective biological functions. Such information can then be utilized to design antibiotic drugs that can compete with essential interactions involving the target and thus interrupt the biological pathways essential for survival of the microorganism(s). LBDD methods focus on known antibiotic ligands for a target to establish a relationship between their physiochemical properties and antibiotic activities, referred to as a structure-activity relationship (SAR), information that can be used for optimization of known drugs or guide the design of new drugs with improved activity. In this chapter, standard CADD protocols for both SBDD and LBDD will be presented with a special focus on methodologies and targets routinely studied in our laboratory for antibiotic drug discoveries.

A statistical view of FMRFamide neuropeptide diversity.

PubMed

Espinoza, E; Carrigan, M; Thomas, S G; Shaw, G; Edison, A S

2000-01-01

FMRFamide-like peptide (FLP) amino acid sequences have been collected and statistically analyzed. FLP amino acid composition as a function of position in the peptide is graphically presented for several major phyla. Results of total amino acid composition and frequencies of pairs of FLP amino acids have been computed and compared with corresponding values from the entire GenBank protein sequence database. The data for pairwise distributions of amino acids should help in future structure-function studies of FLPs. To aid in future peptide discovery, a computer program and search protocol was developed to identify FLPs from the GenBank protein database without the use of keywords.

In silico discovery and in vitro activity of inhibitors against Mycobacterium tuberculosis 7,8-diaminopelargonic acid synthase (Mtb BioA).

PubMed

Billones, Junie B; Carrillo, Maria Constancia O; Organo, Voltaire G; Sy, Jamie Bernadette A; Clavio, Nina Abigail B; Macalino, Stephani Joy Y; Emnacen, Inno A; Lee, Alexandra P; Ko, Paul Kenny L; Concepcion, Gisela P

2017-01-01

Computer-aided drug discovery and development approaches such as virtual screening, molecular docking, and in silico drug property calculations have been utilized in this effort to discover new lead compounds against tuberculosis. The enzyme 7,8-diaminopelargonic acid aminotransferase (BioA) in Mycobacterium tuberculosis ( Mtb ), primarily involved in the lipid biosynthesis pathway, was chosen as the drug target due to the fact that humans are not capable of synthesizing biotin endogenously. The computational screening of 4.5 million compounds from the Enamine REAL database has ultimately yielded 45 high-scoring, high-affinity compounds with desirable in silico absorption, distribution, metabolism, excretion, and toxicity properties. Seventeen of the 45 compounds were subjected to bioactivity validation using the resazurin microtiter assay. Among the 4 actives, compound 7 (( Z )- N -(2-isopropoxyphenyl)-2-oxo-2-((3-(trifluoromethyl)cyclohexyl)amino)acetimidic acid) displayed inhibitory activity up to 83% at 10 μg/mL concentration against the growth of the Mtb H37Ra strain.

In silico discovery and in vitro activity of inhibitors against Mycobacterium tuberculosis 7,8-diaminopelargonic acid synthase (Mtb BioA)

PubMed Central

Billones, Junie B; Carrillo, Maria Constancia O; Organo, Voltaire G; Sy, Jamie Bernadette A; Clavio, Nina Abigail B; Macalino, Stephani Joy Y; Emnacen, Inno A; Lee, Alexandra P; Ko, Paul Kenny L; Concepcion, Gisela P

2017-01-01

Computer-aided drug discovery and development approaches such as virtual screening, molecular docking, and in silico drug property calculations have been utilized in this effort to discover new lead compounds against tuberculosis. The enzyme 7,8-diaminopelargonic acid aminotransferase (BioA) in Mycobacterium tuberculosis (Mtb), primarily involved in the lipid biosynthesis pathway, was chosen as the drug target due to the fact that humans are not capable of synthesizing biotin endogenously. The computational screening of 4.5 million compounds from the Enamine REAL database has ultimately yielded 45 high-scoring, high-affinity compounds with desirable in silico absorption, distribution, metabolism, excretion, and toxicity properties. Seventeen of the 45 compounds were subjected to bioactivity validation using the resazurin microtiter assay. Among the 4 actives, compound 7 ((Z)-N-(2-isopropoxyphenyl)-2-oxo-2-((3-(trifluoromethyl)cyclohexyl)amino)acetimidic acid) displayed inhibitory activity up to 83% at 10 μg/mL concentration against the growth of the Mtb H37Ra strain. PMID:28280303

Modern approaches to accelerate discovery of new antischistosomal drugs.

PubMed

Neves, Bruno Junior; Muratov, Eugene; Machado, Renato Beilner; Andrade, Carolina Horta; Cravo, Pedro Vitor Lemos

2016-06-01

The almost exclusive use of only praziquantel for the treatment of schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes. Consequently, there is an urgent need for new antischistosomal drugs. The identification of leads and the generation of high quality data are crucial steps in the early stages of schistosome drug discovery projects. Herein, the authors focus on the current developments in antischistosomal lead discovery, specifically referring to the use of automated in vitro target-based and whole-organism screens and virtual screening of chemical databases. They highlight the strengths and pitfalls of each of the above-mentioned approaches, and suggest possible roadmaps towards the integration of several strategies, which may contribute for optimizing research outputs and led to more successful and cost-effective drug discovery endeavors. Increasing partnerships and access to funding for drug discovery have strengthened the battle against schistosomiasis in recent years. However, the authors believe this battle also includes innovative strategies to overcome scientific challenges. In this context, significant advances of in vitro screening as well as computer-aided drug discovery have contributed to increase the success rate and reduce the costs of drug discovery campaigns. Although some of these approaches were already used in current antischistosomal lead discovery pipelines, the integration of these strategies in a solid workflow should allow the production of new treatments for schistosomiasis in the near future.

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

24 CFR 180.500 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Discovery. 180.500 Section 180.500... OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Discovery § 180.500 Discovery. (a) In general. This subpart governs discovery in aid of administrative proceedings under this part. Discovery in...

Lessons learned from the design of chemical space networks and opportunities for new applications.

PubMed

Vogt, Martin; Stumpfe, Dagmar; Maggiora, Gerald M; Bajorath, Jürgen

2016-03-01

The concept of chemical space is of fundamental relevance in chemical informatics and computer-aided drug discovery. In a series of articles published in the Journal of Computer-Aided Molecular Design, principles of chemical space design were evaluated, molecular networks proposed as an alternative to conventional coordinate-based chemical reference spaces, and different types of chemical space networks (CSNs) constructed and analyzed. Central to the generation of CSNs was the way in which molecular similarity relationships were assessed and a primary focal point was the network-based representation of biologically relevant chemical space. The design and comparison of CSNs based upon alternative similarity measures can be viewed as an evolutionary path with interesting lessons learned along the way. CSN design has matured to the point that such chemical space representations can be used in practice. In this contribution, highlights from the sequence of CSN design efforts are discussed in context, providing a perspective for future practical applications.

Lessons learned from the design of chemical space networks and opportunities for new applications

NASA Astrophysics Data System (ADS)

Vogt, Martin; Stumpfe, Dagmar; Maggiora, Gerald M.; Bajorath, Jürgen

2016-03-01

The concept of chemical space is of fundamental relevance in chemical informatics and computer-aided drug discovery. In a series of articles published in the Journal of Computer- Aided Molecular Design, principles of chemical space design were evaluated, molecular networks proposed as an alternative to conventional coordinate-based chemical reference spaces, and different types of chemical space networks (CSNs) constructed and analyzed. Central to the generation of CSNs was the way in which molecular similarity relationships were assessed and a primary focal point was the network-based representation of biologically relevant chemical space. The design and comparison of CSNs based upon alternative similarity measures can be viewed as an evolutionary path with interesting lessons learned along the way. CSN design has matured to the point that such chemical space representations can be used in practice. In this contribution, highlights from the sequence of CSN design efforts are discussed in context, providing a perspective for future practical applications.

A machine learning approach to computer-aided molecular design

NASA Astrophysics Data System (ADS)

Bolis, Giorgio; Di Pace, Luigi; Fabrocini, Filippo

1991-12-01

Preliminary results of a machine learning application concerning computer-aided molecular design applied to drug discovery are presented. The artificial intelligence techniques of machine learning use a sample of active and inactive compounds, which is viewed as a set of positive and negative examples, to allow the induction of a molecular model characterizing the interaction between the compounds and a target molecule. The algorithm is based on a twofold phase. In the first one — the specialization step — the program identifies a number of active/inactive pairs of compounds which appear to be the most useful in order to make the learning process as effective as possible and generates a dictionary of molecular fragments, deemed to be responsible for the activity of the compounds. In the second phase — the generalization step — the fragments thus generated are combined and generalized in order to select the most plausible hypothesis with respect to the sample of compounds. A knowledge base concerning physical and chemical properties is utilized during the inductive process.

Metabolic characterization of cultured mammalian cells by mass balance analysis, tracer labeling experiments and computer-aided simulations.

PubMed

Okahashi, Nobuyuki; Kohno, Susumu; Kitajima, Shunsuke; Matsuda, Fumio; Takahashi, Chiaki; Shimizu, Hiroshi

2015-12-01

Studying metabolic directions and flow rates in cultured mammalian cells can provide key information for understanding metabolic function in the fields of cancer research, drug discovery, stem cell biology, and antibody production. In this work, metabolic engineering methodologies including medium component analysis, (13)C-labeling experiments, and computer-aided simulation analysis were applied to characterize the metabolic phenotype of soft tissue sarcoma cells derived from p53-null mice. Cells were cultured in medium containing [1-(13)C] glutamine to assess the level of reductive glutamine metabolism via the reverse reaction of isocitrate dehydrogenase (IDH). The specific uptake and production rates of glucose, organic acids, and the 20 amino acids were determined by time-course analysis of cultured media. Gas chromatography-mass spectrometry analysis of the (13)C-labeling of citrate, succinate, fumarate, malate, and aspartate confirmed an isotopically steady state of the cultured cells. After removing the effect of naturally occurring isotopes, the direction of the IDH reaction was determined by computer-aided analysis. The results validated that metabolic engineering methodologies are applicable to soft tissue sarcoma cells derived from p53-null mice, and also demonstrated that reductive glutamine metabolism is active in p53-null soft tissue sarcoma cells under normoxia. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Discovery radiomics via evolutionary deep radiomic sequencer discovery for pathologically proven lung cancer detection.

PubMed

Shafiee, Mohammad Javad; Chung, Audrey G; Khalvati, Farzad; Haider, Masoom A; Wong, Alexander

2017-10-01

While lung cancer is the second most diagnosed form of cancer in men and women, a sufficiently early diagnosis can be pivotal in patient survival rates. Imaging-based, or radiomics-driven, detection methods have been developed to aid diagnosticians, but largely rely on hand-crafted features that may not fully encapsulate the differences between cancerous and healthy tissue. Recently, the concept of discovery radiomics was introduced, where custom abstract features are discovered from readily available imaging data. We propose an evolutionary deep radiomic sequencer discovery approach based on evolutionary deep intelligence. Motivated by patient privacy concerns and the idea of operational artificial intelligence, the evolutionary deep radiomic sequencer discovery approach organically evolves increasingly more efficient deep radiomic sequencers that produce significantly more compact yet similarly descriptive radiomic sequences over multiple generations. As a result, this framework improves operational efficiency and enables diagnosis to be run locally at the radiologist's computer while maintaining detection accuracy. We evaluated the evolved deep radiomic sequencer (EDRS) discovered via the proposed evolutionary deep radiomic sequencer discovery framework against state-of-the-art radiomics-driven and discovery radiomics methods using clinical lung CT data with pathologically proven diagnostic data from the LIDC-IDRI dataset. The EDRS shows improved sensitivity (93.42%), specificity (82.39%), and diagnostic accuracy (88.78%) relative to previous radiomics approaches.

Open Innovation Drug Discovery (OIDD): a potential path to novel therapeutic chemical space.

PubMed

Alvim-Gaston, Maria; Grese, Timothy; Mahoui, Abdelaziz; Palkowitz, Alan D; Pineiro-Nunez, Marta; Watson, Ian

2014-01-01

The continued development of computational and synthetic methods has enabled the enumeration or preparation of a nearly endless universe of chemical structures. Nevertheless, the ability of this chemical universe to deliver small molecules that can both modulate biological targets and have drug-like physicochemical properties continues to be a topic of interest to the pharmaceutical industry and academic researchers alike. The chemical space described by public, commercial, in-house and virtual compound collections has been interrogated by multiple approaches including biochemical, cellular and virtual screening, diversity analysis, and in-silico profiling. However, current drugs and known chemical probes derived from these efforts are contained within a remarkably small volume of the predicted chemical space. Access to more diverse classes of chemical scaffolds that maintain the properties relevant for drug discovery is certainly needed to meet the increasing demands for pharmaceutical innovation. The Lilly Open Innovation Drug Discovery platform (OIDD) was designed to tackle barriers to innovation through the identification of novel molecules active in relevant disease biology models. In this article we will discuss several computational approaches towards describing novel, biologically active, drug-like chemical space and illustrate how the OIDD program may facilitate access to previously untapped molecules that may aid in the search for innovative pharmaceuticals.

CUAHSI Data Services: Tools and Cyberinfrastructure for Water Data Discovery, Research and Collaboration

NASA Astrophysics Data System (ADS)

Seul, M.; Brazil, L.; Castronova, A. M.

2017-12-01

CUAHSI Data Services: Tools and Cyberinfrastructure for Water Data Discovery, Research and CollaborationEnabling research surrounding interdisciplinary topics often requires a combination of finding, managing, and analyzing large data sets and models from multiple sources. This challenge has led the National Science Foundation to make strategic investments in developing community data tools and cyberinfrastructure that focus on water data, as it is central need for many of these research topics. CUAHSI (The Consortium of Universities for the Advancement of Hydrologic Science, Inc.) is a non-profit organization funded by the National Science Foundation to aid students, researchers, and educators in using and managing data and models to support research and education in the water sciences. This presentation will focus on open-source CUAHSI-supported tools that enable enhanced data discovery online using advanced searching capabilities and computational analysis run in virtual environments pre-designed for educators and scientists so they can focus their efforts on data analysis rather than IT set-up.

QSAR studies in the discovery of novel type-II diabetic therapies.

PubMed

Abuhammad, Areej; Taha, Mutasem O

2016-01-01

Type-II diabetes mellitus (T2DM) is a complex chronic disease that represents a major therapeutic challenge. Despite extensive efforts in T2DM drug development, therapies remain unsatisfactory. Currently, there are many novel and important antidiabetic drug targets under investigation by many research groups worldwide. One of the main challenges to develop effective orally active hypoglycemic agents is off-target effects. Computational tools have impacted drug discovery at many levels. One of the earliest methods is quantitative structure-activity relationship (QSAR) studies. QSAR strategies help medicinal chemists understand the relationship between hypoglycemic activity and molecular properties. Hence, QSAR may hold promise in guiding the synthesis of specifically designed novel ligands that demonstrate high potency and target selectivity. This review aims to provide an overview of the QSAR strategies used to model antidiabetic agents. In particular, this review focuses on drug targets that raised recent scientific interest and/or led to successful antidiabetic agents in the market. Special emphasis has been made on studies that led to the identification of novel antidiabetic scaffolds. Computer-aided molecular design and discovery techniques like QSAR have a great potential in designing leads against complex diseases such as T2DM. Combined with other in silico techniques, QSAR can provide more useful and rational insights to facilitate the discovery of novel compounds. However, since T2DM is a complex disease that includes several faulty biological targets, multi-target QSAR studies are recommended in the future to achieve efficient antidiabetic therapies.

24 CFR 26.43 - Subpoenas.

Code of Federal Regulations, 2010 CFR

2010-04-01

... PROCEDURES Hearings Pursuant to the Administrative Procedure Act Discovery § 26.43 Subpoenas. (a) General... request for a subpoena in aid of discovery shall be filed in time to permit the conclusion of discovery 15...

77 FR 75459 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of a Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-20

... both sides would participate in an Exchange Auction, this proposed change would aid in price discovery... auction price. This proposed change would aid in price discovery and help to reduce the likelihood of... Sell Shares and, therefore, a User would never have complete knowledge of liquidity available on both...

Industrial applications of high-performance computing for phylogeny reconstruction

NASA Astrophysics Data System (ADS)

Bader, David A.; Moret, Bernard M.; Vawter, Lisa

2001-07-01

Phylogenies (that is, tree-of-life relationships) derived from gene order data may prove crucial in answering some fundamental open questions in biomolecular evolution. Real-world interest is strong in determining these relationships. For example, pharmaceutical companies may use phylogeny reconstruction in drug discovery for discovering synthetic pathways unique to organisms that they wish to target. Health organizations study the phylogenies of organisms such as HIV in order to understand their epidemiologies and to aid in predicting the behaviors of future outbreaks. And governments are interested in aiding the production of such foodstuffs as rice, wheat and potatoes via genetics through understanding of the phylogenetic distribution of genetic variation in wild populations. Yet few techniques are available for difficult phylogenetic reconstruction problems. Appropriate tools for analysis of such data may aid in resolving some of the phylogenetic problems that have been analyzed without much resolution for decades. With the rapid accumulation of whole genome sequences for a wide diversity of taxa, especially microbial taxa, phylogenetic reconstruction based on changes in gene order and gene content is showing promise, particularly for resolving deep (i.e., ancient) branch splits. However, reconstruction from gene-order data is even more computationally expensive than reconstruction from sequence data, particularly in groups with large numbers of genes and highly-rearranged genomes. We have developed a software suite, GRAPPA, that extends the breakpoint analysis (BPAnalysis) method of Sankoff and Blanchette while running much faster: in a recent analysis of chloroplast genome data for species of Campanulaceae on a 512-processor Linux supercluster with Myrinet, we achieved a one-million-fold speedup over BPAnalysis. GRAPPA can use either breakpoint or inversion distance (computed exactly) for its computation and runs on single-processor machines as well as parallel and high-performance computers.

Assessment of composite motif discovery methods.

PubMed

Klepper, Kjetil; Sandve, Geir K; Abul, Osman; Johansen, Jostein; Drablos, Finn

2008-02-26

Computational discovery of regulatory elements is an important area of bioinformatics research and more than a hundred motif discovery methods have been published. Traditionally, most of these methods have addressed the problem of single motif discovery - discovering binding motifs for individual transcription factors. In higher organisms, however, transcription factors usually act in combination with nearby bound factors to induce specific regulatory behaviours. Hence, recent focus has shifted from single motifs to the discovery of sets of motifs bound by multiple cooperating transcription factors, so called composite motifs or cis-regulatory modules. Given the large number and diversity of methods available, independent assessment of methods becomes important. Although there have been several benchmark studies of single motif discovery, no similar studies have previously been conducted concerning composite motif discovery. We have developed a benchmarking framework for composite motif discovery and used it to evaluate the performance of eight published module discovery tools. Benchmark datasets were constructed based on real genomic sequences containing experimentally verified regulatory modules, and the module discovery programs were asked to predict both the locations of these modules and to specify the single motifs involved. To aid the programs in their search, we provided position weight matrices corresponding to the binding motifs of the transcription factors involved. In addition, selections of decoy matrices were mixed with the genuine matrices on one dataset to test the response of programs to varying levels of noise. Although some of the methods tested tended to score somewhat better than others overall, there were still large variations between individual datasets and no single method performed consistently better than the rest in all situations. The variation in performance on individual datasets also shows that the new benchmark datasets represents a suitable variety of challenges to most methods for module discovery.

Discovery of novel biomarkers and phenotypes by semantic technologies

PubMed Central

2013-01-01

Background Biomarkers and target-specific phenotypes are important to targeted drug design and individualized medicine, thus constituting an important aspect of modern pharmaceutical research and development. More and more, the discovery of relevant biomarkers is aided by in silico techniques based on applying data mining and computational chemistry on large molecular databases. However, there is an even larger source of valuable information available that can potentially be tapped for such discoveries: repositories constituted by research documents. Results This paper reports on a pilot experiment to discover potential novel biomarkers and phenotypes for diabetes and obesity by self-organized text mining of about 120,000 PubMed abstracts, public clinical trial summaries, and internal Merck research documents. These documents were directly analyzed by the InfoCodex semantic engine, without prior human manipulations such as parsing. Recall and precision against established, but different benchmarks lie in ranges up to 30% and 50% respectively. Retrieval of known entities missed by other traditional approaches could be demonstrated. Finally, the InfoCodex semantic engine was shown to discover new diabetes and obesity biomarkers and phenotypes. Amongst these were many interesting candidates with a high potential, although noticeable noise (uninteresting or obvious terms) was generated. Conclusions The reported approach of employing autonomous self-organising semantic engines to aid biomarker discovery, supplemented by appropriate manual curation processes, shows promise and has potential to impact, conservatively, a faster alternative to vocabulary processes dependent on humans having to read and analyze all the texts. More optimistically, it could impact pharmaceutical research, for example to shorten time-to-market of novel drugs, or speed up early recognition of dead ends and adverse reactions. PMID:23402646

Fifty years of herbicide research: comparing the discovery of trifluralin and halauxifen-methyl.

PubMed

Epp, Jeffrey B; Schmitzer, Paul R; Crouse, Gary D

2018-01-01

Fifty years separate the commercialization of the herbicides trifluralin and halauxifen-methyl. Despite the vast degree of technological change that occurred over that time frame, some aspects of their discovery stories are remarkably similar. For example, both herbicides were prepared very early in the iterative discovery process and both were developed from known lead compound structures by hypothesis-driven research efforts without the use of in vitro assays or computer-aided molecular design. However, there are aspects of the halauxifen-methyl and trifluralin discovery stories that are substantially different. For example, the chemical technology required for the cost-effective production of halauxifen-methyl simply did not exist just two decades prior to its commercial launch. By contrast, the chemical technology required for the cost-effective production of trifluralin was reported in the chemical literature more than two decades prior to its commercial launch. In addition, changes in regulatory environment since the early 1960s ensured that their respective discovery to commercial launch stories would also differ in substantial ways. Ultimately, the time and cost required to develop and register halauxifen-methyl demanded a global initial business case while the lower registration hurdles that trifluralin cleared enabled a narrow initial business case mainly focused on the USA. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Distinctive Behaviors of Druggable Proteins in Cellular Networks

PubMed Central

Workman, Paul; Al-Lazikani, Bissan

2015-01-01

The interaction environment of a protein in a cellular network is important in defining the role that the protein plays in the system as a whole, and thus its potential suitability as a drug target. Despite the importance of the network environment, it is neglected during target selection for drug discovery. Here, we present the first systematic, comprehensive computational analysis of topological, community and graphical network parameters of the human interactome and identify discriminatory network patterns that strongly distinguish drug targets from the interactome as a whole. Importantly, we identify striking differences in the network behavior of targets of cancer drugs versus targets from other therapeutic areas and explore how they may relate to successful drug combinations to overcome acquired resistance to cancer drugs. We develop, computationally validate and provide the first public domain predictive algorithm for identifying druggable neighborhoods based on network parameters. We also make available full predictions for 13,345 proteins to aid target selection for drug discovery. All target predictions are available through canSAR.icr.ac.uk. Underlying data and tools are available at https://cansar.icr.ac.uk/cansar/publications/druggable_network_neighbourhoods/. PMID:26699810

Computer-assisted initial diagnosis of rare diseases

PubMed Central

Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert

2016-01-01

Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534

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

PubMed

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 compounds. An android application of ChemDP is available at its website. The ChemDP is freely accessible at www.chemdp.com.

HIV- and AIDS-associated cancers.

PubMed

Carr, Ellen R

2013-04-01

One of the most significant world epidemics in history, HIV/AIDS, has been a research priority since its discovery in 1981. This review article provides an update on HIV/AIDS, with a specific focus on the diagnosis and care of patients with HIV- and AIDS-associated cancers.

Development and Validation of a Computational Model Ensemble for the Early Detection of BCRP/ABCG2 Substrates during the Drug Design Stage.

PubMed

Gantner, Melisa E; Peroni, Roxana N; Morales, Juan F; Villalba, María L; Ruiz, María E; Talevi, Alan

2017-08-28

Breast Cancer Resistance Protein (BCRP) is an ATP-dependent efflux transporter linked to the multidrug resistance phenomenon in many diseases such as epilepsy and cancer and a potential source of drug interactions. For these reasons, the early identification of substrates and nonsubstrates of this transporter during the drug discovery stage is of great interest. We have developed a computational nonlinear model ensemble based on conformational independent molecular descriptors using a combined strategy of genetic algorithms, J48 decision tree classifiers, and data fusion. The best model ensemble consists in averaging the ranking of the 12 decision trees that showed the best performance on the training set, which also demonstrated a good performance for the test set. It was experimentally validated using the ex vivo everted rat intestinal sac model. Five anticonvulsant drugs classified as nonsubstrates for BRCP by the model ensemble were experimentally evaluated, and none of them proved to be a BCRP substrate under the experimental conditions used, thus confirming the predictive ability of the model ensemble. The model ensemble reported here is a potentially valuable tool to be used as an in silico ADME filter in computer-aided drug discovery campaigns intended to overcome BCRP-mediated multidrug resistance issues and to prevent drug-drug interactions.

Computer-aided discovery of debris disk candidates: A case study using the Wide-Field Infrared Survey Explorer (WISE) catalog

NASA Astrophysics Data System (ADS)

Nguyen, T.; Pankratius, V.; Eckman, L.; Seager, S.

2018-04-01

Debris disks around stars other than the Sun have received significant attention in studies of exoplanets, specifically exoplanetary system formation. Since debris disks are major sources of infrared emissions, infrared survey data such as the Wide-Field Infrared Survey (WISE) catalog potentially harbors numerous debris disk candidates. However, it is currently challenging to perform disk candidate searches for over 747 million sources in the WISE catalog due to the high probability of false positives caused by interstellar matter, galaxies, and other background artifacts. Crowdsourcing techniques have thus started to harness citizen scientists for debris disk identification since humans can be easily trained to distinguish between desired artifacts and irrelevant noises. With a limited number of citizen scientists, however, increasing data volumes from large surveys will inevitably lead to analysis bottlenecks. To overcome this scalability problem and push the current limits of automated debris disk candidate identification, we present a novel approach that uses citizen science results as a seed to train machine learning based classification. In this paper, we detail a case study with a computer-aided discovery pipeline demonstrating such feasibility based on WISE catalog data and NASA's Disk Detective project. Our approach of debris disk candidates classification was shown to be robust under a wide range of image quality and features. Our hybrid approach of citizen science with algorithmic scalability can facilitate big data processing for future detections as envisioned in future missions such as the Transiting Exoplanet Survey Satellite (TESS) and the Wide-Field Infrared Survey Telescope (WFIRST).

Advancing Drug Discovery through Enhanced Free Energy Calculations.

PubMed

Abel, Robert; Wang, Lingle; Harder, Edward D; Berne, B J; Friesner, Richard A

2017-07-18

A principal goal of drug discovery project is to design molecules that can tightly and selectively bind to the target protein receptor. Accurate prediction of protein-ligand binding free energies is therefore of central importance in computational chemistry and computer aided drug design. Multiple recent improvements in computing power, classical force field accuracy, enhanced sampling methods, and simulation setup have enabled accurate and reliable calculations of protein-ligands binding free energies, and position free energy calculations to play a guiding role in small molecule drug discovery. In this Account, we outline the relevant methodological advances, including the REST2 (Replica Exchange with Solute Temperting) enhanced sampling, the incorporation of REST2 sampling with convential FEP (Free Energy Perturbation) through FEP/REST, the OPLS3 force field, and the advanced simulation setup that constitute our FEP+ approach, followed by the presentation of extensive comparisons with experiment, demonstrating sufficient accuracy in potency prediction (better than 1 kcal/mol) to substantially impact lead optimization campaigns. The limitations of the current FEP+ implementation and best practices in drug discovery applications are also discussed followed by the future methodology development plans to address those limitations. We then report results from a recent drug discovery project, in which several thousand FEP+ calculations were successfully deployed to simultaneously optimize potency, selectivity, and solubility, illustrating the power of the approach to solve challenging drug design problems. The capabilities of free energy calculations to accurately predict potency and selectivity have led to the advance of ongoing drug discovery projects, in challenging situations where alternative approaches would have great difficulties. The ability to effectively carry out projects evaluating tens of thousands, or hundreds of thousands, of proposed drug candidates, is potentially transformative in enabling hard to drug targets to be attacked, and in facilitating the development of superior compounds, in various dimensions, for a wide range of targets. More effective integration of FEP+ calculations into the drug discovery process will ensure that the results are deployed in an optimal fashion for yielding the best possible compounds entering the clinic; this is where the greatest payoff is in the exploitation of computer driven design capabilities. A key conclusion from the work described is the surprisingly robust and accurate results that are attainable within the conventional classical simulation, fixed charge paradigm. No doubt there are individual cases that would benefit from a more sophisticated energy model or dynamical treatment, and properties other than protein-ligand binding energies may be more sensitive to these approximations. We conclude that an inflection point in the ability of MD simulations to impact drug discovery has now been attained, due to the confluence of hardware and software development along with the formulation of "good enough" theoretical methods and models.

Recent development on computer aided tissue engineering--a review.

PubMed

Sun, Wei; Lal, Pallavi

2002-02-01

The utilization of computer-aided technologies in tissue engineering has evolved in the development of a new field of computer-aided tissue engineering (CATE). This article reviews recent development and application of enabling computer technology, imaging technology, computer-aided design and computer-aided manufacturing (CAD and CAM), and rapid prototyping (RP) technology in tissue engineering, particularly, in computer-aided tissue anatomical modeling, three-dimensional (3-D) anatomy visualization and 3-D reconstruction, CAD-based anatomical modeling, computer-aided tissue classification, computer-aided tissue implantation and prototype modeling assisted surgical planning and reconstruction.

Discovery of 2-((1H-benzo[d]imidazol-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-4-ones as novel PKM2 activators.

PubMed

Guo, Chuangxing; Linton, Angelica; Jalaie, Mehran; Kephart, Susan; Ornelas, Martha; Pairish, Mason; Greasley, Samantha; Richardson, Paul; Maegley, Karen; Hickey, Michael; Li, John; Wu, Xin; Ji, Xiaodong; Xie, Zhi

2013-06-01

The M2 isoform of pyruvate kinase is an emerging target for antitumor therapy. In this letter, we describe the discovery of 2-((1H-benzo[d]imidazol-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-4-ones as potent and selective PKM2 activators which were found to have a novel binding mode. The original lead identified from high throughput screening was optimized into an efficient series via computer-aided structure-based drug design. Both a representative compound from this series and an activator described in the literature were used as molecular tools to probe the biological effects of PKM2 activation on cancer cells. Our results suggested that PKM2 activation alone is not sufficient to alter cancer cell metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

Big Biomedical data as the key resource for discovery science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toga, Arthur W.; Foster, Ian; Kesselman, Carl

Modern biomedical data collection is generating exponentially more data in a multitude of formats. This flood of complex data poses significant opportunities to discover and understand the critical interplay among such diverse domains as genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics, and clinical data. The Big Data for Discovery Science Center is taking an “-ome to home” approach to discover linkages between these disparate data sources by mining existing databases of proteomic and genomic data, brain images, and clinical assessments. In support of this work, the authors developed new technological capabilities that make it easy for researchers to manage,more » aggregate, manipulate, integrate, and model large amounts of distributed data. Guided by biological domain expertise, the Center’s computational resources and software will reveal relationships and patterns, aiding researchers in identifying biomarkers for the most confounding conditions and diseases, such as Parkinson’s and Alzheimer’s.« less

Big biomedical data as the key resource for discovery science

PubMed Central

Toga, Arthur W; Foster, Ian; Kesselman, Carl; Madduri, Ravi; Chard, Kyle; Deutsch, Eric W; Price, Nathan D; Glusman, Gustavo; Heavner, Benjamin D; Dinov, Ivo D; Ames, Joseph; Van Horn, John; Kramer, Roger; Hood, Leroy

2015-01-01

Modern biomedical data collection is generating exponentially more data in a multitude of formats. This flood of complex data poses significant opportunities to discover and understand the critical interplay among such diverse domains as genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics, and clinical data. The Big Data for Discovery Science Center is taking an “-ome to home” approach to discover linkages between these disparate data sources by mining existing databases of proteomic and genomic data, brain images, and clinical assessments. In support of this work, the authors developed new technological capabilities that make it easy for researchers to manage, aggregate, manipulate, integrate, and model large amounts of distributed data. Guided by biological domain expertise, the Center’s computational resources and software will reveal relationships and patterns, aiding researchers in identifying biomarkers for the most confounding conditions and diseases, such as Parkinson’s and Alzheimer’s. PMID:26198305

Machine-Learning Techniques Applied to Antibacterial Drug Discovery

PubMed Central

Durrant, Jacob D.; Amaro, Rommie E.

2014-01-01

The emergence of drug-resistant bacteria threatens to catapult humanity back to the pre-antibiotic era. Even now, multi-drug-resistant bacterial infections annually result in millions of hospital days, billions in healthcare costs, and, most importantly, tens of thousands of lives lost. As many pharmaceutical companies have abandoned antibiotic development in search of more lucrative therapeutics, academic researchers are uniquely positioned to fill the resulting vacuum. Traditional high-throughput screens and lead-optimization efforts are expensive and labor intensive. Computer-aided drug discovery techniques, which are cheaper and faster, can accelerate the identification of novel antibiotics in an academic setting, leading to improved hit rates and faster transitions to pre-clinical and clinical testing. The current review describes two machine-learning techniques, neural networks and decision trees, that have been used to identify experimentally validated antibiotics. We conclude by describing the future directions of this exciting field. PMID:25521642

Computational drug discovery

PubMed Central

Ou-Yang, Si-sheng; Lu, Jun-yan; Kong, Xiang-qian; Liang, Zhong-jie; Luo, Cheng; Jiang, Hualiang

2012-01-01

Computational drug discovery is an effective strategy for accelerating and economizing drug discovery and development process. Because of the dramatic increase in the availability of biological macromolecule and small molecule information, the applicability of computational drug discovery has been extended and broadly applied to nearly every stage in the drug discovery and development workflow, including target identification and validation, lead discovery and optimization and preclinical tests. Over the past decades, computational drug discovery methods such as molecular docking, pharmacophore modeling and mapping, de novo design, molecular similarity calculation and sequence-based virtual screening have been greatly improved. In this review, we present an overview of these important computational methods, platforms and successful applications in this field. PMID:22922346

Applying Knowledge of Enzyme Biochemistry to the Prediction of Functional Sites for Aiding Drug Discovery.

PubMed

Pai, Priyadarshini P; Mondal, Sukanta

2017-01-01

Enzymes are biological catalysts that play an important role in determining the patterns of chemical transformations pertaining to life. Many milestones have been achieved in unraveling the mechanisms in which the enzymes orchestrate various cellular processes using experimental and computational approaches. Experimental studies generating nearly all possible mutations of target enzymes have been aided by rapid computational approaches aiming at enzyme functional classification, understanding domain organization, functional site identification. The functional architecture, essentially, is involved in binding or interaction with ligands including substrates, products, cofactors, inhibitors, providing for their function, such as in catalysis, ligand mediated cell signaling, allosteric regulation and post-translational modifications. With the increasing availability of enzyme information and advances in algorithm development, computational approaches have now become more capable of providing precise inputs for enzyme engineering, and in the process also making it more efficient. This has led to interesting findings, especially in aberrant enzyme interactions, such as hostpathogen interactions in infection, neurodegenerative diseases, cancer and diabetes. This review aims to summarize in retrospection - the mined knowledge, vivid perspectives and challenging strides in using available experimentally validated enzyme information for characterization. An analytical outlook is presented on the scope of exploring future directions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drug-Target Interactions: Prediction Methods and Applications.

PubMed

Anusuya, Shanmugam; Kesherwani, Manish; Priya, K Vishnu; Vimala, Antonydhason; Shanmugam, Gnanendra; Velmurugan, Devadasan; Gromiha, M Michael

2018-01-01

Identifying the interactions between drugs and target proteins is a key step in drug discovery. This not only aids to understand the disease mechanism, but also helps to identify unexpected therapeutic activity or adverse side effects of drugs. Hence, drug-target interaction prediction becomes an essential tool in the field of drug repurposing. The availability of heterogeneous biological data on known drug-target interactions enabled many researchers to develop various computational methods to decipher unknown drug-target interactions. This review provides an overview on these computational methods for predicting drug-target interactions along with available webservers and databases for drug-target interactions. Further, the applicability of drug-target interactions in various diseases for identifying lead compounds has been outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

AlloPred: prediction of allosteric pockets on proteins using normal mode perturbation analysis.

PubMed

Greener, Joe G; Sternberg, Michael J E

2015-10-23

Despite being hugely important in biological processes, allostery is poorly understood and no universal mechanism has been discovered. Allosteric drugs are a largely unexplored prospect with many potential advantages over orthosteric drugs. Computational methods to predict allosteric sites on proteins are needed to aid the discovery of allosteric drugs, as well as to advance our fundamental understanding of allostery. AlloPred, a novel method to predict allosteric pockets on proteins, was developed. AlloPred uses perturbation of normal modes alongside pocket descriptors in a machine learning approach that ranks the pockets on a protein. AlloPred ranked an allosteric pocket top for 23 out of 40 known allosteric proteins, showing comparable and complementary performance to two existing methods. In 28 of 40 cases an allosteric pocket was ranked first or second. The AlloPred web server, freely available at http://www.sbg.bio.ic.ac.uk/allopred/home, allows visualisation and analysis of predictions. The source code and dataset information are also available from this site. Perturbation of normal modes can enhance our ability to predict allosteric sites on proteins. Computational methods such as AlloPred assist drug discovery efforts by suggesting sites on proteins for further experimental study.

The AIDS and Cancer Specimen Resource: Role in HIV/AIDS scientific discovery

PubMed Central

Ayers, Leona W; Silver, Sylvia; McGrath, Michael S; Orenstein, Jan M

2007-01-01

The AIDS Cancer and Specimen Resource (ACSR) supports scientific discovery in the area of HIV/AIDS-associated malignancies. The ACSR was established as a cooperative agreement between the NCI (Office of the Director, Division of Cancer Treatment and Diagnosis) and regional consortia, University of California, San Francisco (West Coast), George Washington University (East Coast) and Ohio State University (Mid-Region) to collect, preserve and disperse HIV-related tissues and biologic fluids and controls along with clinical data to qualified investigators. The available biological samples with clinical data and the application process are described on the ACSR web site. The ACSR tissue bank has more than 100,000 human HIV positive specimens that represent different processing (43), specimen (15), and anatomical site (50) types. The ACSR provides special biospecimen collections and prepares speciality items, e.g., tissue microarrays (TMA), DNA libraries. Requests have been greatest for Kaposi's sarcoma (32%) and non-Hodgkin's lymphoma (26%). Dispersed requests include 83% tissue (frozen and paraffin embedded), 18% plasma/serum and 9% other. ACSR also provides tissue microarrays of, e.g., Kaposi's sarcoma and non-Hodgkin's lymphoma, for biomarker assays and has developed collaborations with other groups that provide access to additional AIDS-related malignancy specimens. ACSR members and associates have completed 63 podium and poster presentations. Investigators have submitted 125 letters of intent requests. Discoveries using ACSR have been reported in 61 scientific publications in notable journals with an average impact factor of 7. The ACSR promotes the scientific exploration of the relationship between HIV/AIDS and malignancy by participation at national and international scientific meetings, contact with investigators who have productive research in this area and identifying, collecting, preserving, enhancing, and dispersing HIV/AIDS-related malignancy specimens to funded, approved researchers at no fee. Scientific discovery has been advanced by this unique biorepository. Investigators are encouraged to browse the ACSR Internet site for materials to enhance their own scientific initiatives. PMID:17335575

Pulmonary lobar volumetry using novel volumetric computer-aided diagnosis and computed tomography

PubMed Central

Iwano, Shingo; Kitano, Mariko; Matsuo, Keiji; Kawakami, Kenichi; Koike, Wataru; Kishimoto, Mariko; Inoue, Tsutomu; Li, Yuanzhong; Naganawa, Shinji

2013-01-01

OBJECTIVES To compare the accuracy of pulmonary lobar volumetry using the conventional number of segments method and novel volumetric computer-aided diagnosis using 3D computed tomography images. METHODS We acquired 50 consecutive preoperative 3D computed tomography examinations for lung tumours reconstructed at 1-mm slice thicknesses. We calculated the lobar volume and the emphysematous lobar volume < −950 HU of each lobe using (i) the slice-by-slice method (reference standard), (ii) number of segments method, and (iii) semi-automatic and (iv) automatic computer-aided diagnosis. We determined Pearson correlation coefficients between the reference standard and the three other methods for lobar volumes and emphysematous lobar volumes. We also compared the relative errors among the three measurement methods. RESULTS Both semi-automatic and automatic computer-aided diagnosis results were more strongly correlated with the reference standard than the number of segments method. The correlation coefficients for automatic computer-aided diagnosis were slightly lower than those for semi-automatic computer-aided diagnosis because there was one outlier among 50 cases (2%) in the right upper lobe and two outliers among 50 cases (4%) in the other lobes. The number of segments method relative error was significantly greater than those for semi-automatic and automatic computer-aided diagnosis (P < 0.001). The computational time for automatic computer-aided diagnosis was 1/2 to 2/3 than that of semi-automatic computer-aided diagnosis. CONCLUSIONS A novel lobar volumetry computer-aided diagnosis system could more precisely measure lobar volumes than the conventional number of segments method. Because semi-automatic computer-aided diagnosis and automatic computer-aided diagnosis were complementary, in clinical use, it would be more practical to first measure volumes by automatic computer-aided diagnosis, and then use semi-automatic measurements if automatic computer-aided diagnosis failed. PMID:23526418

A historical reflection on the discovery of human retroviruses.

PubMed

Vahlne, Anders

2009-05-01

The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined. The first human retroviruses (HTLV-I) was first reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma and coworkers in 1981. These discoveries were in turn dependent on the previous discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor as it was called then. HTLV-II was described by Gallo's group in 1982. A human retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the morphology of a lentivirus was in my mind described for the first time by Luc Montagnier in an oral presentation at Cold Spring Harbor in September of 1983. This virus was isolated from a patient with lymphadenopathy using the protocol previously described for HTLV by Gallo. The first peer reviewed paper by Montagnier's group of such a retrovirus, isolated from two siblings of whom one with AIDS, appeared in Lancet in April of 1984. However, the proof that a new human retrovirus (HIV-1) was the cause of AIDS was first established in four publications by Gallo's group in the May 4th issue of Science in 1984.

Machine Learning in Medical Imaging.

PubMed

Giger, Maryellen L

2018-03-01

Advances in both imaging and computers have synergistically led to a rapid rise in the potential use of artificial intelligence in various radiological imaging tasks, such as risk assessment, detection, diagnosis, prognosis, and therapy response, as well as in multi-omics disease discovery. A brief overview of the field is given here, allowing the reader to recognize the terminology, the various subfields, and components of machine learning, as well as the clinical potential. Radiomics, an expansion of computer-aided diagnosis, has been defined as the conversion of images to minable data. The ultimate benefit of quantitative radiomics is to (1) yield predictive image-based phenotypes of disease for precision medicine or (2) yield quantitative image-based phenotypes for data mining with other -omics for discovery (ie, imaging genomics). For deep learning in radiology to succeed, note that well-annotated large data sets are needed since deep networks are complex, computer software and hardware are evolving constantly, and subtle differences in disease states are more difficult to perceive than differences in everyday objects. In the future, machine learning in radiology is expected to have a substantial clinical impact with imaging examinations being routinely obtained in clinical practice, providing an opportunity to improve decision support in medical image interpretation. The term of note is decision support, indicating that computers will augment human decision making, making it more effective and efficient. The clinical impact of having computers in the routine clinical practice may allow radiologists to further integrate their knowledge with their clinical colleagues in other medical specialties and allow for precision medicine. Copyright © 2018. Published by Elsevier Inc.

A computational chemistry perspective on the current status and future direction of hepatitis B antiviral drug discovery.

PubMed

Morgnanesi, Dante; Heinrichs, Eric J; Mele, Anthony R; Wilkinson, Sean; Zhou, Suzanne; Kulp, John L

2015-11-01

Computational chemical biology, applied to research on hepatitis B virus (HBV), has two major branches: bioinformatics (statistical models) and first-principle methods (molecular physics). While bioinformatics focuses on statistical tools and biological databases, molecular physics uses mathematics and chemical theory to study the interactions of biomolecules. Three computational techniques most commonly used in HBV research are homology modeling, molecular docking, and molecular dynamics. Homology modeling is a computational simulation to predict protein structure and has been used to construct conformers of the viral polymerase (reverse transcriptase domain and RNase H domain) and the HBV X protein. Molecular docking is used to predict the most likely orientation of a ligand when it is bound to a protein, as well as determining an energy score of the docked conformation. Molecular dynamics is a simulation that analyzes biomolecule motions and determines conformation and stability patterns. All of these modeling techniques have aided in the understanding of resistance mutations on HBV non-nucleos(t)ide reverse-transcriptase inhibitor binding. Finally, bioinformatics can be used to study the DNA and RNA protein sequences of viruses to both analyze drug resistance and to genotype the viral genomes. Overall, with these techniques, and others, computational chemical biology is becoming more and more necessary in hepatitis B research. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B." Copyright © 2015 Elsevier B.V. All rights reserved.

HIV in Young Adults: An Exploration of Knowledge and Risk

ERIC Educational Resources Information Center

Sabato, Todd

2015-01-01

Over three decades since its discovery, HIV/AIDS remains a critical public health challenge. An estimated 1.41 million AIDS cases, and approximately 659,000 AIDS-related deaths, were reported to the Centers for Disease Control and Prevention (CDC) through 2013 (Stine, 2013). While 53% of documented AIDS cases in the United States have occurred…

Computational approaches for drug discovery.

PubMed

Hung, Che-Lun; Chen, Chi-Chun

2014-09-01

Cellular proteins are the mediators of multiple organism functions being involved in physiological mechanisms and disease. By discovering lead compounds that affect the function of target proteins, the target diseases or physiological mechanisms can be modulated. Based on knowledge of the ligand-receptor interaction, the chemical structures of leads can be modified to improve efficacy, selectivity and reduce side effects. One rational drug design technology, which enables drug discovery based on knowledge of target structures, functional properties and mechanisms, is computer-aided drug design (CADD). The application of CADD can be cost-effective using experiments to compare predicted and actual drug activity, the results from which can used iteratively to improve compound properties. The two major CADD-based approaches are structure-based drug design, where protein structures are required, and ligand-based drug design, where ligand and ligand activities can be used to design compounds interacting with the protein structure. Approaches in structure-based drug design include docking, de novo design, fragment-based drug discovery and structure-based pharmacophore modeling. Approaches in ligand-based drug design include quantitative structure-affinity relationship and pharmacophore modeling based on ligand properties. Based on whether the structure of the receptor and its interaction with the ligand are known, different design strategies can be seed. After lead compounds are generated, the rule of five can be used to assess whether these have drug-like properties. Several quality validation methods, such as cost function analysis, Fisher's cross-validation analysis and goodness of hit test, can be used to estimate the metrics of different drug design strategies. To further improve CADD performance, multi-computers and graphics processing units may be applied to reduce costs. © 2014 Wiley Periodicals, Inc.

The Application of Computer-Aided Discovery to Spacecraft Site Selection

NASA Astrophysics Data System (ADS)

Pankratius, V.; Blair, D. M.; Gowanlock, M.; Herring, T.

2015-12-01

The selection of landing and exploration sites for interplanetary robotic or human missions is a complex task. Historically it has been labor-intensive, with large groups of scientists manually interpreting a planetary surface across a variety of datasets to identify potential sites based on science and engineering constraints. This search process can be lengthy, and excellent sites may get overlooked when the aggregate value of site selection criteria is non-obvious or non-intuitive. As planetary data collection leads to Big Data repositories and a growing set of selection criteria, scientists will face a combinatorial search space explosion that requires scalable, automated assistance. We are currently exploring more general computer-aided discovery techniques in the context of planetary surface deformation phenomena that can lend themselves to application in the landing site search problem. In particular, we are developing a general software framework that addresses key difficulties: characterizing a given phenomenon or site based on data gathered from multiple instruments (e.g. radar interferometry, gravity, thermal maps, or GPS time series), and examining a variety of possible workflows whose individual configurations are optimized to isolate different features. The framework allows algorithmic pipelines and hypothesized models to be perturbed or permuted automatically within well-defined bounds established by the scientist. For example, even simple choices for outlier and noise handling or data interpolation can drastically affect the detectability of certain features. These techniques aim to automate repetitive tasks that scientists routinely perform in exploratory analysis, and make them more efficient and scalable by executing them in parallel in the cloud. We also explore ways in which machine learning can be combined with human feedback to prune the search space and converge to desirable results. Acknowledgements: We acknowledge support from NASA AIST NNX15AG84G (PI V. Pankratius)

Building Cognition: The Construction of Computational Representations for Scientific Discovery

ERIC Educational Resources Information Center

Chandrasekharan, Sanjay; Nersessian, Nancy J.

2015-01-01

Novel computational representations, such as simulation models of complex systems and video games for scientific discovery (Foldit, EteRNA etc.), are dramatically changing the way discoveries emerge in science and engineering. The cognitive roles played by such computational representations in discovery are not well understood. We present a…

Computer-aided discovery of two novel chalcone-like compounds active and selective against Leishmania infantum.

PubMed

Gomes, Marcelo N; Alcântara, Laura M; Neves, Bruno J; Melo-Filho, Cleber C; Freitas-Junior, Lucio H; Moraes, Carolina B; Ma, Rui; Franzblau, Scott G; Muratov, Eugene; Andrade, Carolina Horta

2017-06-01

Leishmaniasis are infectious diseases caused by parasites of genus Leishmania that affect affects 12 million people in 98 countries mainly in Africa, Asia, and Latin America. Effective treatments for this disease are urgently needed. In this study, we present a computer-aided approach to investigate a set of 32 recently synthesized chalcone and chalcone-like compounds to act as antileishmanial agents. As a result, nine most promising compounds and three potentially inactive compounds were experimentally evaluated against Leishmania infantum amastigotes and mammalian cells. Four compounds exhibited EC 50 in the range of 6.2-10.98μM. In addition, two compounds, LabMol-65 and LabMol-73, exhibited cytotoxicity in macrophages >50μM that resulted in better selectivity compared to standard drug amphotericin B. These two compounds also demonstrated low cytotoxicity and high selectivity towards Vero cells. The results of target fishing followed by homology modeling and docking studies suggest that these chalcone compounds could act in Leishmania because of their interaction with cysteine proteases, such as procathepsin L. Finally, we have provided structural recommendations for designing new antileishmanial chalcones. Copyright © 2017 Elsevier Ltd. All rights reserved.

Amplify scientific discovery with artificial intelligence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gil, Yolanda; Greaves, Mark T.; Hendler, James

Computing innovations have fundamentally changed many aspects of scientific inquiry. For example, advances in robotics, high-end computing, networking, and databases now underlie much of what we do in science such as gene sequencing, general number crunching, sharing information between scientists, and analyzing large amounts of data. As computing has evolved at a rapid pace, so too has its impact in science, with the most recent computing innovations repeatedly being brought to bear to facilitate new forms of inquiry. Recently, advances in Artificial Intelligence (AI) have deeply penetrated many consumer sectors, including for example Apple’s Siri™ speech recognition system, real-time automatedmore » language translation services, and a new generation of self-driving cars and self-navigating drones. However, AI has yet to achieve comparable levels of penetration in scientific inquiry, despite its tremendous potential in aiding computers to help scientists tackle tasks that require scientific reasoning. We contend that advances in AI will transform the practice of science as we are increasingly able to effectively and jointly harness human and machine intelligence in the pursuit of major scientific challenges.« less

Implementing WebGL and HTML5 in Macromolecular Visualization and Modern Computer-Aided Drug Design.

PubMed

Yuan, Shuguang; Chan, H C Stephen; Hu, Zhenquan

2017-06-01

Web browsers have long been recognized as potential platforms for remote macromolecule visualization. However, the difficulty in transferring large-scale data to clients and the lack of native support for hardware-accelerated applications in the local browser undermine the feasibility of such utilities. With the introduction of WebGL and HTML5 technologies in recent years, it is now possible to exploit the power of a graphics-processing unit (GPU) from a browser without any third-party plugin. Many new tools have been developed for biological molecule visualization and modern drug discovery. In contrast to traditional offline tools, real-time computing, interactive data analysis, and cross-platform analyses feature WebGL- and HTML5-based tools, facilitating biological research in a more efficient and user-friendly way. Copyright © 2017 Elsevier Ltd. All rights reserved.

Computational design of molecules for an all-quinone redox flow battery.

PubMed

Er, Süleyman; Suh, Changwon; Marshak, Michael P; Aspuru-Guzik, Alán

2015-02-01

Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH 2 ) ( i.e. , two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships.

A Software Engineering Approach based on WebML and BPMN to the Mediation Scenario of the SWS Challenge

NASA Astrophysics Data System (ADS)

Brambilla, Marco; Ceri, Stefano; Valle, Emanuele Della; Facca, Federico M.; Tziviskou, Christina

Although Semantic Web Services are expected to produce a revolution in the development of Web-based systems, very few enterprise-wide design experiences are available; one of the main reasons is the lack of sound Software Engineering methods and tools for the deployment of Semantic Web applications. In this chapter, we present an approach to software development for the Semantic Web based on classical Software Engineering methods (i.e., formal business process development, computer-aided and component-based software design, and automatic code generation) and on semantic methods and tools (i.e., ontology engineering, semantic service annotation and discovery).

Computational analysis of EBNA1 ``druggability'' suggests novel insights for Epstein-Barr virus inhibitor design

NASA Astrophysics Data System (ADS)

Gianti, Eleonora; Messick, Troy E.; Lieberman, Paul M.; Zauhar, Randy J.

2016-04-01

The Epstein-Barr Nuclear Antigen 1 (EBNA1) is a critical protein encoded by the Epstein-Barr Virus (EBV). During latent infection, EBNA1 is essential for DNA replication and transcription initiation of viral and cellular genes and is necessary to immortalize primary B-lymphocytes. Nonetheless, the concept of EBNA1 as drug target is novel. Two EBNA1 crystal structures are publicly available and the first small-molecule EBNA1 inhibitors were recently discovered. However, no systematic studies have been reported on the structural details of EBNA1 "druggable" binding sites. We conducted computational identification and structural characterization of EBNA1 binding pockets, likely to accommodate ligand molecules (i.e. "druggable" binding sites). Then, we validated our predictions by docking against a set of compounds previously tested in vitro for EBNA1 inhibition (PubChem AID-2381). Finally, we supported assessments of pocket druggability by performing induced fit docking and molecular dynamics simulations paired with binding affinity predictions by Molecular Mechanics Generalized Born Surface Area calculations for a number of hits belonging to druggable binding sites. Our results establish EBNA1 as a target for drug discovery, and provide the computational evidence that active AID-2381 hits disrupt EBNA1:DNA binding upon interacting at individual sites. Lastly, structural properties of top scoring hits are proposed to support the rational design of the next generation of EBNA1 inhibitors.

Predictive compound accumulation rules yield a broad-spectrum antibiotic

NASA Astrophysics Data System (ADS)

Richter, Michelle F.; Drown, Bryon S.; Riley, Andrew P.; Garcia, Alfredo; Shirai, Tomohiro; Svec, Riley L.; Hergenrother, Paul J.

2017-05-01

Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs against these pathogens challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negative bacteria is largely based on retrospective analyses of antibacterial agents, which suggest that polarity and molecular weight are key factors. Here we assess the ability of over 180 diverse compounds to accumulate in Escherichia coli. Computational analysis of the results reveals major differences from the retrospective studies, namely that the small molecules that are most likely to accumulate contain an amine, are amphiphilic and rigid, and have low globularity. These guidelines were then applied to convert deoxynybomycin, a natural product that is active only against Gram-positive organisms, into an antibiotic with activity against a diverse panel of multi-drug-resistant Gram-negative pathogens. We anticipate that these findings will aid in the discovery and development of antibiotics against Gram-negative bacteria.

Predictive rules for compound accumulation yield a broad-spectrum antibiotic

PubMed Central

Richter, Michelle F.; Drown, Bryon S.; Riley, Andrew P.; Garcia, Alfredo; Shirai, Tomohiro; Svec, Riley L.; Hergenrother, Paul J.

2017-01-01

Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs for these pathogens very challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negatives is largely based on retrospective analyses of antibacterials that suggest polarity and molecular weight as key factors. Here we assess the ability of over 180 diverse compounds to accumulate in Escherichia coli. Computational analysis of the results reveals major differences from the retrospective studies, namely that the small molecules that are most likely to accumulate contain an amine, are amphiphilic and rigid, and have low globularity. These guidelines were then applied to convert deoxynybomycin, a natural product that is active only against Gram-positive organisms, into an antibiotic with activity against a diverse panel of multi-drug-resistant Gram-negative pathogens. We anticipate these findings will aid in the discovery and development of antibiotics effective against Gram-negative bacteria. PMID:28489819

Synthetic biology to access and expand nature’s chemical diversity

PubMed Central

Smanski, Michael J.; Zhou, Hui; Claesen, Jan; Shen, Ben; Fischbach, Michael; Voigt, Christopher A.

2016-01-01

Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Economically accessing the potential encoded within sequenced genomes promises to reinvigorate waning drug discovery pipelines and provide novel routes to intricate chemicals. This is a tremendous undertaking, as the pathways often comprise dozens of genes spanning as much as 100+ kiliobases of DNA, are controlled by complex regulatory networks, and the most interesting molecules are made by non-model organisms. Advances in synthetic biology address these issues, including DNA construction technologies, genetic parts for precision expression control, synthetic regulatory circuits, computer aided design, and multiplexed genome engineering. Collectively, these technologies are moving towards an era when chemicals can be accessed en mass based on sequence information alone. This will enable the harnessing of metagenomic data and massive strain banks for high-throughput molecular discovery and, ultimately, the ability to forward design pathways to complex chemicals not found in nature. PMID:26876034

Big biomedical data as the key resource for discovery science.

PubMed

Toga, Arthur W; Foster, Ian; Kesselman, Carl; Madduri, Ravi; Chard, Kyle; Deutsch, Eric W; Price, Nathan D; Glusman, Gustavo; Heavner, Benjamin D; Dinov, Ivo D; Ames, Joseph; Van Horn, John; Kramer, Roger; Hood, Leroy

2015-11-01

Modern biomedical data collection is generating exponentially more data in a multitude of formats. This flood of complex data poses significant opportunities to discover and understand the critical interplay among such diverse domains as genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics, and clinical data. The Big Data for Discovery Science Center is taking an "-ome to home" approach to discover linkages between these disparate data sources by mining existing databases of proteomic and genomic data, brain images, and clinical assessments. In support of this work, the authors developed new technological capabilities that make it easy for researchers to manage, aggregate, manipulate, integrate, and model large amounts of distributed data. Guided by biological domain expertise, the Center's computational resources and software will reveal relationships and patterns, aiding researchers in identifying biomarkers for the most confounding conditions and diseases, such as Parkinson's and Alzheimer's. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Network-Based Approaches in Drug Discovery and Early Development

PubMed Central

Harrold, JM; Ramanathan, M; Mager, DE

2015-01-01

Identification of novel targets is a critical first step in the drug discovery and development process. Most diseases such as cancer, metabolic disorders, and neurological disorders are complex, and their pathogenesis involves multiple genetic and environmental factors. Finding a viable drug target–drug combination with high potential for yielding clinical success within the efficacy–toxicity spectrum is extremely challenging. Many examples are now available in which network-based approaches show potential for the identification of novel targets and for the repositioning of established targets. The objective of this article is to highlight network approaches for identifying novel targets with greater chances of gaining approved drugs with maximal efficacy and minimal side effects. Further enhancement of these approaches may emerge from effectively integrating computational systems biology with pharmacodynamic systems analysis. Coupling genomics, proteomics, and metabolomics databases with systems pharmacology modeling may aid in the development of disease-specific networks that can be further used to build confidence in target identification. PMID:24025802

Computational design of molecules for an all-quinone redox flow battery† †Electronic supplementary information (ESI) available: The list of computationally predicted candidate quinone molecules with interesting redox properties. See DOI: 10.1039/c4sc03030c Click here for additional data file.

PubMed Central

Er, Süleyman; Suh, Changwon; Marshak, Michael P.

2015-01-01

Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH2) (i.e., two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships. PMID:29560173

Computational Study on New Natural Compound Inhibitors of Pyruvate Dehydrogenase Kinases

PubMed Central

Zhou, Xiaoli; Yu, Shanshan; Su, Jing; Sun, Liankun

2016-01-01

Pyruvate dehydrogenase kinases (PDKs) are key enzymes in glucose metabolism, negatively regulating pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibiting PDKs could upregulate PDC activity and drive cells into more aerobic metabolism. Therefore, PDKs are potential targets for metabolism related diseases, such as cancers and diabetes. In this study, a series of computer-aided virtual screening techniques were utilized to discover potential inhibitors of PDKs. Structure-based screening using Libdock was carried out following by ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was used to analyze the binding mechanism between these compounds and PDKs. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. From the computational results, two novel natural coumarins compounds (ZINC12296427 and ZINC12389251) from the ZINC database were found binding to PDKs with favorable interaction energy and predicted to be non-toxic. Our study provide valuable information of PDK-coumarins binding mechanisms in PDK inhibitor-based drug discovery. PMID:26959013

Computational Study on New Natural Compound Inhibitors of Pyruvate Dehydrogenase Kinases.

PubMed

Zhou, Xiaoli; Yu, Shanshan; Su, Jing; Sun, Liankun

2016-03-04

Pyruvate dehydrogenase kinases (PDKs) are key enzymes in glucose metabolism, negatively regulating pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibiting PDKs could upregulate PDC activity and drive cells into more aerobic metabolism. Therefore, PDKs are potential targets for metabolism related diseases, such as cancers and diabetes. In this study, a series of computer-aided virtual screening techniques were utilized to discover potential inhibitors of PDKs. Structure-based screening using Libdock was carried out following by ADME (adsorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was used to analyze the binding mechanism between these compounds and PDKs. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. From the computational results, two novel natural coumarins compounds (ZINC12296427 and ZINC12389251) from the ZINC database were found binding to PDKs with favorable interaction energy and predicted to be non-toxic. Our study provide valuable information of PDK-coumarins binding mechanisms in PDK inhibitor-based drug discovery.

Impact of computational structure-based methods on drug discovery.

PubMed

Reynolds, Charles H

2014-01-01

Structure-based drug design has become an indispensible tool in drug discovery. The emergence of structure-based design is due to gains in structural biology that have provided exponential growth in the number of protein crystal structures, new computational algorithms and approaches for modeling protein-ligand interactions, and the tremendous growth of raw computer power in the last 30 years. Computer modeling and simulation have made major contributions to the discovery of many groundbreaking drugs in recent years. Examples are presented that highlight the evolution of computational structure-based design methodology, and the impact of that methodology on drug discovery.

First-Principles Modeling of Hydrogen Storage in Metal Hydride Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

J. Karl Johnson

The objective of this project is to complement experimental efforts of MHoCE partners by using state-of-the-art theory and modeling to study the structure, thermodynamics, and kinetics of hydrogen storage materials. Specific goals include prediction of the heats of formation and other thermodynamic properties of alloys from first principles methods, identification of new alloys that can be tested experimentally, calculation of surface and energetic properties of nanoparticles, and calculation of kinetics involved with hydrogenation and dehydrogenation processes. Discovery of new metal hydrides with enhanced properties compared with existing materials is a critical need for the Metal Hydride Center of Excellence. Newmore » materials discovery can be aided by the use of first principles (ab initio) computational modeling in two ways: (1) The properties, including mechanisms, of existing materials can be better elucidated through a combined modeling/experimental approach. (2) The thermodynamic properties of novel materials that have not been made can, in many cases, be quickly screened with ab initio methods. We have used state-of-the-art computational techniques to explore millions of possible reaction conditions consisting of different element spaces, compositions, and temperatures. We have identified potentially promising single- and multi-step reactions that can be explored experimentally.« less

Reducing Time to Science: Unidata and JupyterHub Technology Using the Jetstream Cloud

NASA Astrophysics Data System (ADS)

Chastang, J.; Signell, R. P.; Fischer, J. L.

2017-12-01

Cloud computing can accelerate scientific workflows, discovery, and collaborations by reducing research and data friction. We describe the deployment of Unidata and JupyterHub technologies on the NSF-funded XSEDE Jetstream cloud. With the aid of virtual machines and Docker technology, we deploy a Unidata JupyterHub server co-located with a Local Data Manager (LDM), THREDDS data server (TDS), and RAMADDA geoscience content management system. We provide Jupyter Notebooks and the pre-built Python environments needed to run them. The notebooks can be used for instruction and as templates for scientific experimentation and discovery. We also supply a large quantity of NCEP forecast model results to allow data-proximate analysis and visualization. In addition, users can transfer data using Globus command line tools, and perform their own data-proximate analysis and visualization with Notebook technology. These data can be shared with others via a dedicated TDS server for scientific distribution and collaboration. There are many benefits of this approach. Not only is the cloud computing environment fast, reliable and scalable, but scientists can analyze, visualize, and share data using only their web browser. No local specialized desktop software or a fast internet connection is required. This environment will enable scientists to spend less time managing their software and more time doing science.

Computer-assisted versus conventional free fibula flap technique for craniofacial reconstruction: an outcomes comparison.

PubMed

Seruya, Mitchel; Fisher, Mark; Rodriguez, Eduardo D

2013-11-01

There has been rising interest in computer-aided design/computer-aided manufacturing for preoperative planning and execution of osseous free flap reconstruction. The purpose of this study was to compare outcomes between computer-assisted and conventional fibula free flap techniques for craniofacial reconstruction. A two-center, retrospective review was carried out on patients who underwent fibula free flap surgery for craniofacial reconstruction from 2003 to 2012. Patients were categorized by the type of reconstructive technique: conventional (between 2003 and 2009) or computer-aided design/computer-aided manufacturing (from 2010 to 2012). Demographics, surgical factors, and perioperative and long-term outcomes were compared. A total of 68 patients underwent microsurgical craniofacial reconstruction: 58 conventional and 10 computer-aided design and manufacturing fibula free flaps. By demographics, patients undergoing the computer-aided design/computer-aided manufacturing method were significantly older and had a higher rate of radiotherapy exposure compared with conventional patients. Intraoperatively, the median number of osteotomies was significantly higher (2.0 versus 1.0, p=0.002) and the median ischemia time was significantly shorter (120 minutes versus 170 minutes, p=0.004) for the computer-aided design/computer-aided manufacturing technique compared with conventional techniques; operative times were shorter for patients undergoing the computer-aided design/computer-aided manufacturing technique, although this did not reach statistical significance. Perioperative and long-term outcomes were equivalent for the two groups, notably, hospital length of stay, recipient-site infection, partial and total flap loss, and rate of soft-tissue and bony tissue revisions. Microsurgical craniofacial reconstruction using a computer-assisted fibula flap technique yielded significantly shorter ischemia times amidst a higher number of osteotomies compared with conventional techniques. Therapeutic, III.

Computer-Aided Facilities Management Systems (CAFM).

ERIC Educational Resources Information Center

Cyros, Kreon L.

Computer-aided facilities management (CAFM) refers to a collection of software used with increasing frequency by facilities managers. The six major CAFM components are discussed with respect to their usefulness and popularity in facilities management applications: (1) computer-aided design; (2) computer-aided engineering; (3) decision support…

Array comparative genomic hybridization and computational genome annotation in constitutional cytogenetics: suggesting candidate genes for novel submicroscopic chromosomal imbalance syndromes.

PubMed

Van Vooren, Steven; Coessens, Bert; De Moor, Bart; Moreau, Yves; Vermeesch, Joris R

2007-09-01

Genome-wide array comparative genomic hybridization screening is uncovering pathogenic submicroscopic chromosomal imbalances in patients with developmental disorders. In those patients, imbalances appear now to be scattered across the whole genome, and most patients carry different chromosomal anomalies. Screening patients with developmental disorders can be considered a forward functional genome screen. The imbalances pinpoint the location of genes that are involved in human development. Because most imbalances encompass regions harboring multiple genes, the challenge is to (1) identify those genes responsible for the specific phenotype and (2) disentangle the role of the different genes located in an imbalanced region. In this review, we discuss novel tools and relevant databases that have recently been developed to aid this gene discovery process. Identification of the functional relevance of genes will not only deepen our understanding of human development but will, in addition, aid in the data interpretation and improve genetic counseling.

The First AIDS Drugs | Center for Cancer Research

Cancer.gov

Faced with the burgeoning HIV/AIDS epidemic in the 1980s, NCI’s intramural program developed the first therapies to effectively treat the disease. These discoveries helped transform a fatal diagnosis to the manageable condition it is for many today.

On the Value of Computer-aided Instruction: Thoughts after Teaching Sales Writing in a Computer Classroom.

ERIC Educational Resources Information Center

Hagge, John

1986-01-01

Focuses on problems encountered with computer-aided writing instruction. Discusses conflicts caused by the computer classroom concept, some general paradoxes and ethical implications of computer-aided instruction. (EL)

Project-Based Teaching-Learning Computer-Aided Engineering Tools

ERIC Educational Resources Information Center

Simoes, J. A.; Relvas, C.; Moreira, R.

2004-01-01

Computer-aided design, computer-aided manufacturing, computer-aided analysis, reverse engineering and rapid prototyping are tools that play an important key role within product design. These are areas of technical knowledge that must be part of engineering and industrial design courses' curricula. This paper describes our teaching experience of…

Is there a best strategy for drug discovery?--SMR Meeting. 13 March 2003, London, UK.

PubMed

Lunec, Anna

2003-05-01

This gathering of members from academia and industry allowed the sharing of ideas and techniques or the acceleration of drug discovery, and it was clear that there is a need for a more streamlined approach to discovery and development. Clearly, new technologies will aid in the discovery process, but the abilities of the human brain to analyze and interpret data should not be overlooked, as many discoveries have been made by chance or as the result of a hunch, and it would be a shame if the advent of artificial intelligence quashed that inquisitive aspect of drug discovery.

Discovery and Development of ATP-Competitive mTOR Inhibitors Using Computational Approaches.

PubMed

Luo, Yao; Wang, Ling

2017-11-16

The mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism, and angiogenesis. This protein is an attractive target for new anticancer drug development. Significant progress has been made in hit discovery, lead optimization, drug candidate development and determination of the three-dimensional (3D) structure of mTOR. Computational methods have been applied to accelerate the discovery and development of mTOR inhibitors helping to model the structure of mTOR, screen compound databases, uncover structure-activity relationship (SAR) and optimize the hits, mine the privileged fragments and design focused libraries. Besides, computational approaches were also applied to study protein-ligand interactions mechanisms and in natural product-driven drug discovery. Herein, we survey the most recent progress on the application of computational approaches to advance the discovery and development of compounds targeting mTOR. Future directions in the discovery of new mTOR inhibitors using computational methods are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Building Cognition: The Construction of Computational Representations for Scientific Discovery.

PubMed

Chandrasekharan, Sanjay; Nersessian, Nancy J

2015-11-01

Novel computational representations, such as simulation models of complex systems and video games for scientific discovery (Foldit, EteRNA etc.), are dramatically changing the way discoveries emerge in science and engineering. The cognitive roles played by such computational representations in discovery are not well understood. We present a theoretical analysis of the cognitive roles such representations play, based on an ethnographic study of the building of computational models in a systems biology laboratory. Specifically, we focus on a case of model-building by an engineer that led to a remarkable discovery in basic bioscience. Accounting for such discoveries requires a distributed cognition (DC) analysis, as DC focuses on the roles played by external representations in cognitive processes. However, DC analyses by and large have not examined scientific discovery, and they mostly focus on memory offloading, particularly how the use of existing external representations changes the nature of cognitive tasks. In contrast, we study discovery processes and argue that discoveries emerge from the processes of building the computational representation. The building process integrates manipulations in imagination and in the representation, creating a coupled cognitive system of model and modeler, where the model is incorporated into the modeler's imagination. This account extends DC significantly, and we present some of the theoretical and application implications of this extended account. Copyright © 2014 Cognitive Science Society, Inc.

Engineering Technology Programs Courses Guide for Computer Aided Design and Computer Aided Manufacturing.

ERIC Educational Resources Information Center

Georgia Univ., Athens. Div. of Vocational Education.

This guide describes the requirements for courses in computer-aided design and computer-aided manufacturing (CAD/CAM) that are part of engineering technology programs conducted in vocational-technical schools in Georgia. The guide is organized in five sections. The first section provides a rationale for occupations in design and in production,…

Employment Opportunities for the Handicapped in Programmable Automation.

ERIC Educational Resources Information Center

Swift, Richard; Leneway, Robert

A Computer Integrated Manufacturing System may make it possible for severely disabled people to custom design, machine, and manufacture either wood or metal parts. Programmable automation merges computer aided design, computer aided manufacturing, computer aided engineering, and computer integrated manufacturing systems with automated production…

Computational and empirical studies predict Mycobacterium tuberculosis-specific T cells as a biomarker for infection outcome

DOE PAGES

Marino, Simeone; Gideon, Hannah P.; Gong, Chang; ...

2016-04-11

Identifying biomarkers for tuberculosis (TB) is an ongoing challenge in developing immunological correlates of infection outcome and protection. Biomarker discovery is also necessary for aiding design and testing of new treatments and vaccines. To effectively predict biomarkers for infection progression in any disease, including TB, large amounts of experimental data are required to reach statistical power and make accurate predictions. We took a two-pronged approach using both experimental and computational modeling to address this problem. We first collected 200 blood samples over a 2-year period from 28 non-human primates (NHP) infected with a low dose of Mycobacterium tuberculosis. We identifiedmore » T cells and the cytokines that they were producing (single and multiple) from each sample along with monkey status and infection progression data. Machine learning techniques were used to interrogate the experimental NHP datasets without identifying any potential TB biomarker. In parallel, we used our extensive novel NHP datasets to build and calibrate a multi-organ computational model that combines what is occurring at the site of infection (e.g., lung) at a single granuloma scale with blood level readouts that can be tracked in monkeys and humans. We then generated a large in silico repository of in silico granulomas coupled to lymph node and blood dynamics and developed an in silico tool to scale granuloma level results to a full host scale to identify what best predicts Mycobacterium tuberculosis (Mtb) infection outcomes. The analysis of in silico blood measures identifies Mtb-specific frequencies of effector T cell phenotypes at various time points post infection as promising indicators of infection outcome. As a result, we emphasize that pairing wetlab and computational approaches holds great promise to accelerate TB biomarker discovery.« less

Computational and empirical studies predict Mycobacterium tuberculosis-specific T cells as a biomarker for infection outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marino, Simeone; Gideon, Hannah P.; Gong, Chang

Identifying biomarkers for tuberculosis (TB) is an ongoing challenge in developing immunological correlates of infection outcome and protection. Biomarker discovery is also necessary for aiding design and testing of new treatments and vaccines. To effectively predict biomarkers for infection progression in any disease, including TB, large amounts of experimental data are required to reach statistical power and make accurate predictions. We took a two-pronged approach using both experimental and computational modeling to address this problem. We first collected 200 blood samples over a 2-year period from 28 non-human primates (NHP) infected with a low dose of Mycobacterium tuberculosis. We identifiedmore » T cells and the cytokines that they were producing (single and multiple) from each sample along with monkey status and infection progression data. Machine learning techniques were used to interrogate the experimental NHP datasets without identifying any potential TB biomarker. In parallel, we used our extensive novel NHP datasets to build and calibrate a multi-organ computational model that combines what is occurring at the site of infection (e.g., lung) at a single granuloma scale with blood level readouts that can be tracked in monkeys and humans. We then generated a large in silico repository of in silico granulomas coupled to lymph node and blood dynamics and developed an in silico tool to scale granuloma level results to a full host scale to identify what best predicts Mycobacterium tuberculosis (Mtb) infection outcomes. The analysis of in silico blood measures identifies Mtb-specific frequencies of effector T cell phenotypes at various time points post infection as promising indicators of infection outcome. As a result, we emphasize that pairing wetlab and computational approaches holds great promise to accelerate TB biomarker discovery.« less

RNA interference for functional genomics and improvement of cotton (Gossypium species)

USDA-ARS?s Scientific Manuscript database

RNA interference (RNAi), is a powerful new technology in the discovery of genetic sequence functions, and has become a valuable tool for functional genomics of cotton (Gossypium ssp.). The rapid adoption of RNAi has replaced previous antisense technology. RNAi has aided in the discovery of function ...

A Proposed Method for the Computer-aided Discovery and Design of High-strength, Ductile Metals

NASA Astrophysics Data System (ADS)

Winter, Ian Stewart

Gum Metal, a class of Ti-Nb alloys, has generated a great deal of interest in the metallurgical community since its development in 2003. These alloys display numerous novel and anomalous properties, many of which only occur after severe plastic deformation has been incurred on the material. Such properties include: super-elasticity, super-coldworkability, Invar and Elinvar behavior, high ductility, as well as high strength. The high strength of gum metal has generated particular enthusiasm as it is on the order of the predicted ideal strength of the material. Many of the properties of gum metal appear to be a direct result of tuning the composition to be near an elastic instability resulting in a high degree of elastic anisotropy. This presents an opportunity for the computer-aided discovery and design of structural materials as the ideal strength and elastic anisotropy can be approximated from the elastic constants. Two approaches are described for searching for this high ansitropy. In the first, The possibility of forming gum metal in Mg is explored by tuning the material to be near the BCC-HCP transition either by pressure or alloying with Li. The second makes use of the Materials Project's elastic constants database, which contains thousands of ordered compounds, in order to screen for gum metal candidates. By defining an elastic anisotropy parameter consistent with the behavior of gum metal and calculating it for all cubic materials in the elastic constants database several gum metal candidates are found. In order to better assess their candidacy information on the intrinsic ductility of these materials is necessary. A method is proposed for calculating the ideal strength and deformation mode of a solid solution from first-principles. In order to validate this method the intrinsic ductile-to-brittle transition composition of Ti-V systems is calculated. It is further shown that this method can be applied to the calculation of an ideal tensile yield surface.

CAD/CAM (Computer Aided Design/Computer Aided Manufacture). A Brief Guide to Materials in the Library of Congress.

ERIC Educational Resources Information Center

Havas, George D.

This brief guide to materials in the Library of Congress (LC) on computer aided design and/or computer aided manufacturing lists reference materials and other information sources under 13 headings: (1) brief introductions; (2) LC subject headings used for such materials; (3) textbooks; (4) additional titles; (5) glossaries and handbooks; (6)…

Caribbean Equal Access Program: HIV/AIDS Information Resources from the National Library of Medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nancy Dancy, NLM, and Wilma Templin-Branner, ORISE

2009-01-01

As the treatment and management of HIV/AIDS continues to evolve with new scientific breakthroughs, treatment discoveries, and management challenges, it is difficult for people living with HIV/AIDS and those who care for them to keep up with the latest information on HIV/AIDS prevention, treatment, and research. The National Library of Medicine, of the National Institutes of Health, has a wealth of health information resources freely available on the Internet to address these needs.

Computational modeling in melanoma for novel drug discovery.

PubMed

Pennisi, Marzio; Russo, Giulia; Di Salvatore, Valentina; Candido, Saverio; Libra, Massimo; Pappalardo, Francesco

2016-06-01

There is a growing body of evidence highlighting the applications of computational modeling in the field of biomedicine. It has recently been applied to the in silico analysis of cancer dynamics. In the era of precision medicine, this analysis may allow the discovery of new molecular targets useful for the design of novel therapies and for overcoming resistance to anticancer drugs. According to its molecular behavior, melanoma represents an interesting tumor model in which computational modeling can be applied. Melanoma is an aggressive tumor of the skin with a poor prognosis for patients with advanced disease as it is resistant to current therapeutic approaches. This review discusses the basics of computational modeling in melanoma drug discovery and development. Discussion includes the in silico discovery of novel molecular drug targets, the optimization of immunotherapies and personalized medicine trials. Mathematical and computational models are gradually being used to help understand biomedical data produced by high-throughput analysis. The use of advanced computer models allowing the simulation of complex biological processes provides hypotheses and supports experimental design. The research in fighting aggressive cancers, such as melanoma, is making great strides. Computational models represent the key component to complement these efforts. Due to the combinatorial complexity of new drug discovery, a systematic approach based only on experimentation is not possible. Computational and mathematical models are necessary for bringing cancer drug discovery into the era of omics, big data and personalized medicine.

Student Achievement in Computer Programming: Lecture vs Computer-Aided Instruction

ERIC Educational Resources Information Center

Tsai, San-Yun W.; Pohl, Norval F.

1978-01-01

This paper discusses a study of the differences in student learning achievement, as measured by four different types of common performance evaluation techniques, in a college-level computer programming course under three teaching/learning environments: lecture, computer-aided instruction, and lecture supplemented with computer-aided instruction.…

DiscoverySpace: an interactive data analysis application

PubMed Central

Robertson, Neil; Oveisi-Fordorei, Mehrdad; Zuyderduyn, Scott D; Varhol, Richard J; Fjell, Christopher; Marra, Marco; Jones, Steven; Siddiqui, Asim

2007-01-01

DiscoverySpace is a graphical application for bioinformatics data analysis. Users can seamlessly traverse references between biological databases and draw together annotations in an intuitive tabular interface. Datasets can be compared using a suite of novel tools to aid in the identification of significant patterns. DiscoverySpace is of broad utility and its particular strength is in the analysis of serial analysis of gene expression (SAGE) data. The application is freely available online. PMID:17210078

Novel opportunities for computational biology and sociology in drug discovery

PubMed Central

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

Silicon Wafer Advanced Packaging (SWAP). Multichip Module (MCM) Foundry Study. Version 2

DTIC Science & Technology

1991-04-08

Next Layer Dielectric Spacing - Additional Metal Thickness Impact on Dielectric Uniformity/Adhiesion. The first step in .!Ie EPerimental design would be... design CAM - computer aided manufacturing CAE - computer aided engineering CALCE - computer aided life cycle engineering center CARMA - computer aided...expansion 5 j- CVD - chemical vapor deposition J . ..- j DA - design automation J , DEC - Digital Equipment Corporation --- DFT - design for testability

The application of computer-aided technologies in automotive styling design

NASA Astrophysics Data System (ADS)

Zheng, Ze-feng; Zhang, Ji; Zheng, Ying

2012-04-01

In automotive industry, outline design is its life and creative design is its soul indeed. Computer-aided technology has been widely used in the automotive industry and more and more attention has been paid. This paper chiefly introduce the application of computer-aided technologies including CAD, CAM and CAE, analyses the process of automotive structural design and describe the development tendency of computer-aided design.

Probing voltage sensing domain of KCNQ2 channel as a potential target to combat epilepsy: a comparative study.

PubMed

Mehta, Pakhuri; Srivastava, Shubham; Choudhary, Bhanwar Singh; Sharma, Manish; Malik, Ruchi

2017-12-01

Multidrug resistance along with side-effects of available anti-epileptic drugs and unavailability of potent and effective agents in submicromolar quantities presents the biggest therapeutic challenges in anti-epileptic drug discovery. The molecular modeling techniques allow us to identify agents with novel structures to match the continuous urge for its discovery. KCNQ2 channel represents one of the validated targets for its therapy. The present study involves identification of newer anti-epileptic agents by means of a computer-aided drug design adaptive protocol involving both structure-based virtual screening of Asinex library using homology model of KCNQ2 and 3D-QSAR based virtual screening with docking analysis, followed by dG bind and ligand efficiency calculations with ADMET studies, of which 20 hits qualified all the criterions. The best ligands of both screenings with least potential for toxicity predicted computationally were then taken for molecular dynamic simulations. All the crucial amino acid interactions were observed in hits of both screenings such as Glu130, Arg207, Arg210 and Phe137. Robustness of docking protocol was analyzed through Receiver operating characteristic (ROC) curve values 0.88 (Area under curve AUC = 0.87) in Standard Precision and 0.84 (AUC = 0.82) in Extra Precision modes. Novelty analysis indicates that these compounds have not been reported previously as anti-epileptic agents.

Discovery and validation of 2-styryl substituted benzoxazin-4-ones as a novel scaffold for rhomboid protease inhibitors.

PubMed

Goel, Parul; Jumpertz, Thorsten; Tichá, Anežka; Ogorek, Isabella; Mikles, David C; Hubalek, Martin; Pietrzik, Claus U; Strisovsky, Kvido; Schmidt, Boris; Weggen, Sascha

2018-05-01

Rhomboids are intramembrane serine proteases with diverse physiological functions in organisms ranging from archaea to humans. Crystal structure analysis has provided a detailed understanding of the catalytic mechanism, and rhomboids have been implicated in various disease contexts. Unfortunately, the design of specific rhomboid inhibitors has lagged behind, and previously described small molecule inhibitors displayed insufficient potency and/or selectivity. Using a computer-aided approach, we focused on the discovery of novel scaffolds with reduced liabilities and the possibility for broad structural variations. Docking studies with the E. coli rhomboid GlpG indicated that 2-styryl substituted benzoxazinones might comprise novel rhomboid inhibitors. Protease in vitro assays confirmed activity of 2-styryl substituted benzoxazinones against GlpG but not against the soluble serine protease α-chymotrypsin. Furthermore, mass spectrometry analysis demonstrated covalent modification of the catalytic residue Ser201, corroborating the predicted mechanism of inhibition and the formation of an acyl enzyme intermediate. In conclusion, 2-styryl substituted benzoxazinones are a novel rhomboid inhibitor scaffold with ample opportunity for optimization. Copyright © 2018 Elsevier Ltd. All rights reserved.

CADRE-SS, an in Silico Tool for Predicting Skin Sensitization Potential Based on Modeling of Molecular Interactions.

PubMed

Kostal, Jakub; Voutchkova-Kostal, Adelina

2016-01-19

Using computer models to accurately predict toxicity outcomes is considered to be a major challenge. However, state-of-the-art computational chemistry techniques can now be incorporated in predictive models, supported by advances in mechanistic toxicology and the exponential growth of computing resources witnessed over the past decade. The CADRE (Computer-Aided Discovery and REdesign) platform relies on quantum-mechanical modeling of molecular interactions that represent key biochemical triggers in toxicity pathways. Here, we present an external validation exercise for CADRE-SS, a variant developed to predict the skin sensitization potential of commercial chemicals. CADRE-SS is a hybrid model that evaluates skin permeability using Monte Carlo simulations, assigns reactive centers in a molecule and possible biotransformations via expert rules, and determines reactivity with skin proteins via quantum-mechanical modeling. The results were promising with an overall very good concordance of 93% between experimental and predicted values. Comparison to performance metrics yielded by other tools available for this endpoint suggests that CADRE-SS offers distinct advantages for first-round screenings of chemicals and could be used as an in silico alternative to animal tests where permissible by legislative programs.

Enhancing an appointment diary on a pocket computer for use by people after brain injury.

PubMed

Wright, P; Rogers, N; Hall, C; Wilson, B; Evans, J; Emslie, H

2001-12-01

People with memory loss resulting from brain injury benefit from purpose-designed memory aids such as appointment diaries on pocket computers. The present study explores the effects of extending the range of memory aids and including games. For 2 months, 12 people who had sustained brain injury were loaned a pocket computer containing three purpose-designed memory aids: diary, notebook and to-do list. A month later they were given another computer with the same memory aids but a different method of text entry (physical keyboard or touch-screen keyboard). Machine order was counterbalanced across participants. Assessment was by interviews during the loan periods, rating scales, performance tests and computer log files. All participants could use the memory aids and ten people (83%) found them very useful. Correlations among the three memory aids were not significant, suggesting individual variation in how they were used. Games did not increase use of the memory aids, nor did loan of the preferred pocket computer (with physical keyboard). Significantly more diary entries were made by people who had previously used other memory aids, suggesting that a better understanding of how to use a range of memory aids could benefit some people with brain injury.

An Engineering View on Megatrends in Radiology: Digitization to Quantitative Tools of Medicine

PubMed Central

Choi, Jaesoon; Yi, Jaeyoun; Choi, Seungwook; Park, Seyoun; Chang, Yongjun; Seo, Joon Beom

2013-01-01

Within six months of the discovery of X-ray in 1895, the technology was used to scan the interior of the human body, paving the way for many innovations in the field of medicine, including an ultrasound device in 1950, a CT scanner in 1972, and MRI in 1980. More recent decades have witnessed developments such as digital imaging using a picture archiving and communication system, computer-aided detection/diagnosis, organ-specific workstations, and molecular, functional, and quantitative imaging. One of the latest technical breakthrough in the field of radiology has been imaging genomics and robotic interventions for biopsy and theragnosis. This review provides an engineering perspective on these developments and several other megatrends in radiology. PMID:23482650

GRANNY, a data bank of chemical analyses of Laramide and younger high-silica rhyolites and granites from Colorado and north-central New Mexico

USGS Publications Warehouse

Steigerwald, Celia H.; Mutschler, Felix E.; Ludington, Steve

1983-01-01

GRANNY is a data bank containing information on 507 chemically analyzed Laramide or younger high-silica rhyolites and granites from Colorado and north-central New Mexico. The data were compiled from both published and unpublished sources. The data bank is designed to aid in the recognition of igneous rocks with a high exploration potential for the discovery of molybdenum (and other lithophile element) deposits. Information on source reference, geographic location, age, mineralogic and petrologic characteristics, major constituent analyses, and trace element analyses for each sample are given. The data bank is available in two formats: 1) paper- or microfiche-hardcopy, and 2) fixed format computer readable magnetic tape.

A metabolic network approach for the identification and prioritization of antimicrobial drug targets

PubMed Central

Chavali, Arvind K.; D’Auria, Kevin M.; Hewlett, Erik L.; Pearson, Richard D.; Papin, Jason A.

2012-01-01

For many infectious diseases, novel treatment options are needed to address problems with cost, toxicity and resistance to current drugs. Systems biology tools can be used to gain valuable insight into pathogenic processes and aid in expediting drug discovery. In the past decade, constraint-based modeling of genome-scale metabolic networks has become widely used. Focusing on pathogen metabolic networks, we review in silico strategies to identify effective drug targets, and we highlight recent successes as well as limitations associated with such computational analyses. We further discuss how accounting for the host environment and even targeting the host may offer new therapeutic options. These systems-level approaches are beginning to provide novel avenues for drug targeting against infectious agents. PMID:22300758

Computer-aided design and computer science technology

NASA Technical Reports Server (NTRS)

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.

Computer Instructional Aids for Undergraduate Control Education.

ERIC Educational Resources Information Center

Volz, Richard A.; And Others

Engineering is coming to rely more and more heavily upon the computer for computations, analyses, and graphic displays which aid the design process. A general purpose simulation system, the Time-shared Automatic Control Laboratory (TACL), and a set of computer-aided design programs, Control Oriented Interactive Graphic Analysis and Design…

Cloud computing approaches to accelerate drug discovery value chain.

PubMed

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.

Evaluation of Microcomputer-Based Operation and Maintenance Management Systems for Army Water/Wastewater Treatment Plant Operation.

DTIC Science & Technology

1986-07-01

COMPUTER-AIDED OPERATION MANAGEMENT SYSTEM ................. 29 Functions of an Off-Line Computer-Aided Operation Management System Applications of...System Comparisons 85 DISTRIBUTION 5V J. • 0. FIGURES Number Page 1 Hardware Components 21 2 Basic Functions of a Computer-Aided Operation Management System...Plant Visits 26 4 Computer-Aided Operation Management Systems Reviewed for Analysis of Basic Functions 29 5 Progress of Software System Installation and

DOE Office of Scientific and Technical Information (OSTI.GOV)

Templin-Branner, W.

As the treatment and management of HIV/AIDS continues to evolve with new scientific breakthroughs, treatment discoveries, and management challenges, it is difficult for people living with HIV/AIDS and those who care for them to keep up with the latest information on HIV/AIDS screening and testing, prevention, treatment, and research. The National Library of Medicine (NLM), of the National Institutes of Health, has a wealth of health information resources freely available on the Internet to address these needs.

The Feasibility of Classifying Breast Masses Using a Computer-Assisted Diagnosis (CAD) System Based on Ultrasound Elastography and BI-RADS Lexicon.

PubMed

Fleury, Eduardo F C; Gianini, Ana Claudia; Marcomini, Karem; Oliveira, Vilmar

2018-01-01

To determine the applicability of a computer-aided diagnostic system strain elastography system for the classification of breast masses diagnosed by ultrasound and scored using the criteria proposed by the breast imaging and reporting data system ultrasound lexicon and to determine the diagnostic accuracy and interobserver variability. This prospective study was conducted between March 1, 2016, and May 30, 2016. A total of 83 breast masses subjected to percutaneous biopsy were included. Ultrasound elastography images before biopsy were interpreted by 3 radiologists with and without the aid of computer-aided diagnostic system for strain elastography. The parameters evaluated by each radiologist results were sensitivity, specificity, and diagnostic accuracy, with and without computer-aided diagnostic system for strain elastography. Interobserver variability was assessed using a weighted κ test and an intraclass correlation coefficient. The areas under the receiver operating characteristic curves were also calculated. The areas under the receiver operating characteristic curve were 0.835, 0.801, and 0.765 for readers 1, 2, and 3, respectively, without computer-aided diagnostic system for strain elastography, and 0.900, 0.926, and 0.868, respectively, with computer-aided diagnostic system for strain elastography. The intraclass correlation coefficient between the 3 readers was 0.6713 without computer-aided diagnostic system for strain elastography and 0.811 with computer-aided diagnostic system for strain elastography. The proposed computer-aided diagnostic system for strain elastography system has the potential to improve the diagnostic performance of radiologists in breast examination using ultrasound associated with elastography.

The Role of Computational Modeling and Simulation in the Total Product Life Cycle of Peripheral Vascular Devices

PubMed Central

Morrison, Tina M.; Dreher, Maureen L.; Nagaraja, Srinidhi; Angelone, Leonardo M.; Kainz, Wolfgang

2018-01-01

The total product life cycle (TPLC) of medical devices has been defined by four stages: discovery and ideation, regulatory decision, product launch, and postmarket monitoring. Manufacturers of medical devices intended for use in the peripheral vasculature, such as stents, inferior vena cava (IVC) filters, and stent-grafts, mainly use computational modeling and simulation (CM&S) to aid device development and design optimization, supplement bench testing for regulatory decisions, and assess postmarket changes or failures. For example, computational solid mechanics and fluid dynamics enable the investigation of design limitations in the ideation stage. To supplement bench data in regulatory submissions, manufactures can evaluate the effects of anatomical characteristics and expected in vivo loading environment on device performance. Manufacturers might also harness CM&S to aid root-cause analyses that are necessary when failures occur postmarket, when the device is exposed to broad clinical use. Once identified, CM&S tools can then be used for redesign to address the failure mode and re-establish the performance profile with the appropriate models. The Center for Devices and Radiological Health (CDRH) wants to advance the use of CM&S for medical devices and supports the development of virtual physiological patients, clinical trial simulations, and personalized medicine. Thus, the purpose of this paper is to describe specific examples of how CM&S is currently used to support regulatory submissions at different phases of the TPLC and to present some of the stakeholder-led initiatives for advancing CM&S for regulatory decision-making. PMID:29479395

The Role of Computational Modeling and Simulation in the Total Product Life Cycle of Peripheral Vascular Devices.

PubMed

Morrison, Tina M; Dreher, Maureen L; Nagaraja, Srinidhi; Angelone, Leonardo M; Kainz, Wolfgang

2017-01-01

The total product life cycle (TPLC) of medical devices has been defined by four stages: discovery and ideation, regulatory decision, product launch, and postmarket monitoring. Manufacturers of medical devices intended for use in the peripheral vasculature, such as stents, inferior vena cava (IVC) filters, and stent-grafts, mainly use computational modeling and simulation (CM&S) to aid device development and design optimization, supplement bench testing for regulatory decisions, and assess postmarket changes or failures. For example, computational solid mechanics and fluid dynamics enable the investigation of design limitations in the ideation stage. To supplement bench data in regulatory submissions, manufactures can evaluate the effects of anatomical characteristics and expected in vivo loading environment on device performance. Manufacturers might also harness CM&S to aid root-cause analyses that are necessary when failures occur postmarket, when the device is exposed to broad clinical use. Once identified, CM&S tools can then be used for redesign to address the failure mode and re-establish the performance profile with the appropriate models. The Center for Devices and Radiological Health (CDRH) wants to advance the use of CM&S for medical devices and supports the development of virtual physiological patients, clinical trial simulations, and personalized medicine. Thus, the purpose of this paper is to describe specific examples of how CM&S is currently used to support regulatory submissions at different phases of the TPLC and to present some of the stakeholder-led initiatives for advancing CM&S for regulatory decision-making.

iDrug: a web-accessible and interactive drug discovery and design platform

PubMed Central

2014-01-01

Background The progress in computer-aided drug design (CADD) approaches over the past decades accelerated the early-stage pharmaceutical research. Many powerful standalone tools for CADD have been developed in academia. As programs are developed by various research groups, a consistent user-friendly online graphical working environment, combining computational techniques such as pharmacophore mapping, similarity calculation, scoring, and target identification is needed. Results We presented a versatile, user-friendly, and efficient online tool for computer-aided drug design based on pharmacophore and 3D molecular similarity searching. The web interface enables binding sites detection, virtual screening hits identification, and drug targets prediction in an interactive manner through a seamless interface to all adapted packages (e.g., Cavity, PocketV.2, PharmMapper, SHAFTS). Several commercially available compound databases for hit identification and a well-annotated pharmacophore database for drug targets prediction were integrated in iDrug as well. The web interface provides tools for real-time molecular building/editing, converting, displaying, and analyzing. All the customized configurations of the functional modules can be accessed through featured session files provided, which can be saved to the local disk and uploaded to resume or update the history work. Conclusions iDrug is easy to use, and provides a novel, fast and reliable tool for conducting drug design experiments. By using iDrug, various molecular design processing tasks can be submitted and visualized simply in one browser without installing locally any standalone modeling softwares. iDrug is accessible free of charge at http://lilab.ecust.edu.cn/idrug. PMID:24955134

Design and Implementation of a Prototype Ontology Aided Knowledge Discovery Assistant (OAKDA) Application

DTIC Science & Technology

2006-12-01

speed of search engines improves the efficiency of such methods, effectiveness is not improved. The objective of this thesis is to construct and test...interest, users are assisted in finding a relevant set of key terms that will aid the search engines in narrowing, widening, or refocusing a Web search

Computer Aided Design: Instructional Manual. The North Dakota High Technology Mobile Laboratory Project.

ERIC Educational Resources Information Center

Cheng, Wan-Lee

This instructional manual contains 12 learning activity packets for use in a workshop in computer-aided design and drafting (CADD). The lessons cover the following topics: introduction to computer graphics and computer-aided design/drafting; coordinate systems; advance space graphics hardware configuration and basic features of the IBM PC…

RASCAL: A Rudimentary Adaptive System for Computer-Aided Learning.

ERIC Educational Resources Information Center

Stewart, John Christopher

Both the background of computer-assisted instruction (CAI) systems in general and the requirements of a computer-aided learning system which would be a reasonable assistant to a teacher are discussed. RASCAL (Rudimentary Adaptive System for Computer-Aided Learning) is a first attempt at defining a CAI system which would individualize the learning…

Making the Long Tail Visible: Social Networking Sites and Independent Music Discovery

ERIC Educational Resources Information Center

Gaffney, Michael; Rafferty, Pauline

2009-01-01

Purpose: The purpose of this paper is to investigate users' knowledge and use of social networking sites and folksonomies to discover if social tagging and folksonomies, within the area of independent music, aid in its information retrieval and discovery. The sites examined in this project are MySpace, Lastfm, Pandora and Allmusic. In addition,…

Computational methods for a three-dimensional model of the petroleum-discovery process

USGS Publications Warehouse

Schuenemeyer, J.H.; Bawiec, W.J.; Drew, L.J.

1980-01-01

A discovery-process model devised by Drew, Schuenemeyer, and Root can be used to predict the amount of petroleum to be discovered in a basin from some future level of exploratory effort: the predictions are based on historical drilling and discovery data. Because marginal costs of discovery and production are a function of field size, the model can be used to make estimates of future discoveries within deposit size classes. The modeling approach is a geometric one in which the area searched is a function of the size and shape of the targets being sought. A high correlation is assumed between the surface-projection area of the fields and the volume of petroleum. To predict how much oil remains to be found, the area searched must be computed, and the basin size and discovery efficiency must be estimated. The basin is assumed to be explored randomly rather than by pattern drilling. The model may be used to compute independent estimates of future oil at different depth intervals for a play involving multiple producing horizons. We have written FORTRAN computer programs that are used with Drew, Schuenemeyer, and Root's model to merge the discovery and drilling information and perform the necessary computations to estimate undiscovered petroleum. These program may be modified easily for the estimation of remaining quantities of commodities other than petroleum. ?? 1980.

Identification of Nanoparticle Prototypes and Archetypes.

PubMed

Fernandez, Michael; Barnard, Amanda S

2015-12-22

High-throughput (HT) computational characterization of nanomaterials is poised to accelerate novel material breakthroughs. The number of possible nanomaterials is increasing exponentially along with their complexity, and so statistical and information technology will play a fundamental role in rationalizing nanomaterials HT data. We demonstrate that multivariate statistical analysis of heterogeneous ensembles can identify the truly significant nanoparticles and their most relevant properties. Virtual samples of diamond nanoparticles and graphene nanoflakes are characterized using clustering and archetypal analysis, where we find that saturated particles are defined by their geometry, while nonsaturated nanoparticles are defined by their carbon chemistry. At the complex hull of the nanostructure spaces, a combination of complex archetypes can efficiency describe a large number of members of the ensembles, whereas the regular shapes that are typically assumed to be representative can only describe a small set of the most regular morphologies. This approach provides a route toward the characterization of computationally intractable virtual nanomaterial spaces, which can aid nanomaterials discovery in the foreseen big data scenario.

BioPAX – A community standard for pathway data sharing

PubMed Central

Demir, Emek; Cary, Michael P.; Paley, Suzanne; Fukuda, Ken; Lemer, Christian; Vastrik, Imre; Wu, Guanming; D’Eustachio, Peter; Schaefer, Carl; Luciano, Joanne; Schacherer, Frank; Martinez-Flores, Irma; Hu, Zhenjun; Jimenez-Jacinto, Veronica; Joshi-Tope, Geeta; Kandasamy, Kumaran; Lopez-Fuentes, Alejandra C.; Mi, Huaiyu; Pichler, Elgar; Rodchenkov, Igor; Splendiani, Andrea; Tkachev, Sasha; Zucker, Jeremy; Gopinath, Gopal; Rajasimha, Harsha; Ramakrishnan, Ranjani; Shah, Imran; Syed, Mustafa; Anwar, Nadia; Babur, Ozgun; Blinov, Michael; Brauner, Erik; Corwin, Dan; Donaldson, Sylva; Gibbons, Frank; Goldberg, Robert; Hornbeck, Peter; Luna, Augustin; Murray-Rust, Peter; Neumann, Eric; Reubenacker, Oliver; Samwald, Matthias; van Iersel, Martijn; Wimalaratne, Sarala; Allen, Keith; Braun, Burk; Whirl-Carrillo, Michelle; Dahlquist, Kam; Finney, Andrew; Gillespie, Marc; Glass, Elizabeth; Gong, Li; Haw, Robin; Honig, Michael; Hubaut, Olivier; Kane, David; Krupa, Shiva; Kutmon, Martina; Leonard, Julie; Marks, Debbie; Merberg, David; Petri, Victoria; Pico, Alex; Ravenscroft, Dean; Ren, Liya; Shah, Nigam; Sunshine, Margot; Tang, Rebecca; Whaley, Ryan; Letovksy, Stan; Buetow, Kenneth H.; Rzhetsky, Andrey; Schachter, Vincent; Sobral, Bruno S.; Dogrusoz, Ugur; McWeeney, Shannon; Aladjem, Mirit; Birney, Ewan; Collado-Vides, Julio; Goto, Susumu; Hucka, Michael; Le Novère, Nicolas; Maltsev, Natalia; Pandey, Akhilesh; Thomas, Paul; Wingender, Edgar; Karp, Peter D.; Sander, Chris; Bader, Gary D.

2010-01-01

BioPAX (Biological Pathway Exchange) is a standard language to represent biological pathways at the molecular and cellular level. Its major use is to facilitate the exchange of pathway data (http://www.biopax.org). Pathway data captures our understanding of biological processes, but its rapid growth necessitates development of databases and computational tools to aid interpretation. However, the current fragmentation of pathway information across many databases with incompatible formats presents barriers to its effective use. BioPAX solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. BioPAX was created through a community process. Through BioPAX, millions of interactions organized into thousands of pathways across many organisms, from a growing number of sources, are available. Thus, large amounts of pathway data are available in a computable form to support visualization, analysis and biological discovery. PMID:20829833

Discovery of Spatio-Temporal Relationships in GRACE, GPS Time Series, and Groundwater Data Using Voronoi Visualizations

NASA Astrophysics Data System (ADS)

Rude, C. M.; Li, J. D.; Rongier, G.; Gowanlock, M.; Herring, T.; Pankratius, V.

2017-12-01

We introduce a data exploration and visualization tool to facilitate the discovery of correlations across geospatial data sets in a computer-aided discovery system. Our approach is based on adaptive Voronoi tessellation maps that can handle spotty data availability, varying sensor density, and resolution at different scales in the same visualization product. Successful applications exploring spatio-temporal relationships are demonstrated on data sets from the Gravity Recovery and Climate Experiment (GRACE), GPS time series from the Plate Boundary Observatory, and groundwater well depth data from USGS, with the objective of understanding the Earth's surface response to changes in terrestrial water storage. Our results reveal that vertical positions in the majority of GPS stations are negatively correlated with terrestrial water storage from GRACE. This is expected if the changes are due to terrestrial water loading deforming the ground. Our application also identifies outliers that warrant further investigation, such as sites with low correlation or positive correlation due to poroelastic expansion. Other analyses reveal that GRACE correlates positively with water levels from wells, but the removal of GRACE non-groundwater components (canopy water, soil moisture, and snow accumulation) using model data from the Global Land Data Assimilation System unexpectedly lowers the correlations, effects which may be related to modeling accuracy and measurement errors. We acknowledge support from NASA AISTNNX15AG84G (PI Pankratius) and NSF ACI1442997 (PI Pankratius).

Efficient discovery of responses of proteins to compounds using active learning

PubMed Central

2014-01-01

Background Drug discovery and development has been aided by high throughput screening methods that detect compound effects on a single target. However, when using focused initial screening, undesirable secondary effects are often detected late in the development process after significant investment has been made. An alternative approach would be to screen against undesired effects early in the process, but the number of possible secondary targets makes this prohibitively expensive. Results This paper describes methods for making this global approach practical by constructing predictive models for many target responses to many compounds and using them to guide experimentation. We demonstrate for the first time that by jointly modeling targets and compounds using descriptive features and using active machine learning methods, accurate models can be built by doing only a small fraction of possible experiments. The methods were evaluated by computational experiments using a dataset of 177 assays and 20,000 compounds constructed from the PubChem database. Conclusions An average of nearly 60% of all hits in the dataset were found after exploring only 3% of the experimental space which suggests that active learning can be used to enable more complete characterization of compound effects than otherwise affordable. The methods described are also likely to find widespread application outside drug discovery, such as for characterizing the effects of a large number of compounds or inhibitory RNAs on a large number of cell or tissue phenotypes. PMID:24884564

A new approach to the rationale discovery of polymeric biomaterials

PubMed Central

Kohn, Joachim; Welsh, William J.; Knight, Doyle

2007-01-01

This paper attempts to illustrate both the need for new approaches to biomaterials discovery as well as the significant promise inherent in the use of combinatorial and computational design strategies. The key observation of this Leading Opinion Paper is that the biomaterials community has been slow to embrace advanced biomaterials discovery tools such as combinatorial methods, high throughput experimentation, and computational modeling in spite of the significant promise shown by these discovery tools in materials science, medicinal chemistry and the pharmaceutical industry. It seems that the complexity of living cells and their interactions with biomaterials has been a conceptual as well as a practical barrier to the use of advanced discovery tools in biomaterials science. However, with the continued increase in computer power, the goal of predicting the biological response of cells in contact with biomaterials surfaces is within reach. Once combinatorial synthesis, high throughput experimentation, and computational modeling are integrated into the biomaterials discovery process, a significant acceleration is possible in the pace of development of improved medical implants, tissue regeneration scaffolds, and gene/drug delivery systems. PMID:17644176

The Discovery of Reverse Transcriptase.

PubMed

Coffin, John M; Fan, Hung

2016-09-29

In 1970 the independent and simultaneous discovery of reverse transcriptase in retroviruses (then RNA tumor viruses) by David Baltimore and Howard Temin revolutionized molecular biology and laid the foundations for retrovirology and cancer biology. In this historical review we describe the formulation of the controversial provirus hypothesis by Temin, which ultimately was proven by his discovery of reverse transcriptase in Rous sarcoma virus virions. Baltimore arrived at the same discovery through his studies on replication of RNA-containing viruses, starting with poliovirus and then moving to vesicular stomatitis virus, where he discovered a virion RNA polymerase. Subsequent studies of reverse transcriptase led to the elucidation of the mechanism of retrovirus replication, the discovery of oncogenes, the advent of molecular cloning, the search for human cancer viruses, and the discovery and treatment of HIV/AIDS.

Rubber airplane: Constraint-based component-modeling for knowledge representation in computer-aided conceptual design

NASA Technical Reports Server (NTRS)

Kolb, Mark A.

1990-01-01

Viewgraphs on Rubber Airplane: Constraint-based Component-Modeling for Knowledge Representation in Computer Aided Conceptual Design are presented. Topics covered include: computer aided design; object oriented programming; airfoil design; surveillance aircraft; commercial aircraft; aircraft design; and launch vehicles.

[Development of computer aided forming techniques in manufacturing scaffolds for bone tissue engineering].

PubMed

Wei, Xuelei; Dong, Fuhui

2011-12-01

To review recent advance in the research and application of computer aided forming techniques for constructing bone tissue engineering scaffolds. The literature concerning computer aided forming techniques for constructing bone tissue engineering scaffolds in recent years was reviewed extensively and summarized. Several studies over last decade have focused on computer aided forming techniques for bone scaffold construction using various scaffold materials, which is based on computer aided design (CAD) and bone scaffold rapid prototyping (RP). CAD include medical CAD, STL, and reverse design. Reverse design can fully simulate normal bone tissue and could be very useful for the CAD. RP techniques include fused deposition modeling, three dimensional printing, selected laser sintering, three dimensional bioplotting, and low-temperature deposition manufacturing. These techniques provide a new way to construct bone tissue engineering scaffolds with complex internal structures. With rapid development of molding and forming techniques, computer aided forming techniques are expected to provide ideal bone tissue engineering scaffolds.

The Impact of Machine Translation and Computer-aided Translation on Translators

NASA Astrophysics Data System (ADS)

Peng, Hao

2018-03-01

Under the context of globalization, communications between countries and cultures are becoming increasingly frequent, which make it imperative to use some techniques to help translate. This paper is to explore the influence of computer-aided translation on translators, which is derived from the field of the computer-aided translation (CAT) and machine translation (MT). Followed by an introduction to the development of machine and computer-aided translation, it then depicts the technologies practicable to translators, which are trying to analyze the demand of designing the computer-aided translation so far in translation practice, and optimize the designation of computer-aided translation techniques, and analyze its operability in translation. The findings underline the advantages and disadvantages of MT and CAT tools, and the serviceability and future development of MT and CAT technologies. Finally, this thesis probes into the impact of these new technologies on translators in hope that more translators and translation researchers can learn to use such tools to improve their productivity.

Using Just-in-Time Information to Support Scientific Discovery Learning in a Computer-Based Simulation

ERIC Educational Resources Information Center

Hulshof, Casper D.; de Jong, Ton

2006-01-01

Students encounter many obstacles during scientific discovery learning with computer-based simulations. It is hypothesized that an effective type of support, that does not interfere with the scientific discovery learning process, should be delivered on a "just-in-time" base. This study explores the effect of facilitating access to…

Computational biology for cardiovascular biomarker discovery.

PubMed

Azuaje, Francisco; Devaux, Yvan; Wagner, Daniel

2009-07-01

Computational biology is essential in the process of translating biological knowledge into clinical practice, as well as in the understanding of biological phenomena based on the resources and technologies originating from the clinical environment. One such key contribution of computational biology is the discovery of biomarkers for predicting clinical outcomes using 'omic' information. This process involves the predictive modelling and integration of different types of data and knowledge for screening, diagnostic or prognostic purposes. Moreover, this requires the design and combination of different methodologies based on statistical analysis and machine learning. This article introduces key computational approaches and applications to biomarker discovery based on different types of 'omic' data. Although we emphasize applications in cardiovascular research, the computational requirements and advances discussed here are also relevant to other domains. We will start by introducing some of the contributions of computational biology to translational research, followed by an overview of methods and technologies used for the identification of biomarkers with predictive or classification value. The main types of 'omic' approaches to biomarker discovery will be presented with specific examples from cardiovascular research. This will include a review of computational methodologies for single-source and integrative data applications. Major computational methods for model evaluation will be described together with recommendations for reporting models and results. We will present recent advances in cardiovascular biomarker discovery based on the combination of gene expression and functional network analyses. The review will conclude with a discussion of key challenges for computational biology, including perspectives from the biosciences and clinical areas.

Ribbon cutting opens new ELV offices

NASA Technical Reports Server (NTRS)

2000-01-01

Viewed from the side, orbiter Discovery, with its seven-member crew, touches down on the landing strip at Edwards Air Force Base, Calif., after an 11-day mission to the International Space Station. The orbiter's main landing gear touched down on EAFB runway 22 at 5 p.m. With the aid of its drag chute, Discovery came to a complete stop at 5:01 p.m. At the conclusion of mission STS-92, Discovery and crew had traveled about 5.3 million statute miles. Following vehicle safing and preliminary offloading efforts, workers will begin preparations for Discovery's transcontinental ferry flight back to KSC on the back of NASA's modified Boeing 747.

Attributes Affecting Computer-Aided Decision Making--A Literature Survey.

ERIC Educational Resources Information Center

Moldafsky, Neil I; Kwon, Ik-Whan

1994-01-01

Reviews current literature about personal, demographic, situational, and cognitive attributes that affect computer-aided decision making. The effectiveness of computer-aided decision making is explored in relation to decision quality, effectiveness, and confidence. Studies of the effects of age, anxiety, cognitive type, attitude, gender, and prior…

User-Centered Computer Aided Language Learning

ERIC Educational Resources Information Center

Zaphiris, Panayiotis, Ed.; Zacharia, Giorgos, Ed.

2006-01-01

In the field of computer aided language learning (CALL), there is a need for emphasizing the importance of the user. "User-Centered Computer Aided Language Learning" presents methodologies, strategies, and design approaches for building interfaces for a user-centered CALL environment, creating a deeper understanding of the opportunities and…

Hearing Impairments. Tech Use Guide: Using Computer Technology.

ERIC Educational Resources Information Center

Council for Exceptional Children, Reston, VA. Center for Special Education Technology.

One of nine brief guides for special educators on using computer technology, this guide focuses on advances in electronic aids, computers, telecommunications, and videodiscs to assist students with hearing impairments. Electronic aids include hearing aids, telephone devices for the deaf, teletypes, closed captioning systems for television, and…

Regulation of AID, the B-cell genome mutator

PubMed Central

Keim, Celia; Kazadi, David; Rothschild, Gerson; Basu, Uttiya

2013-01-01

The mechanisms by which B cells somatically engineer their genomes to generate the vast diversity of antibodies required to challenge the nearly infinite number of antigens that immune systems encounter are of tremendous clinical and academic interest. The DNA cytidine deaminase activation-induced deaminase (AID) catalyzes two of these mechanisms: class switch recombination (CSR) and somatic hypermutation (SHM). Recent discoveries indicate a significant promiscuous targeting of this B-cell mutator enzyme genome-wide. Here we discuss the various regulatory elements that control AID activity and prevent AID from inducing genomic instability and thereby initiating oncogenesis. PMID:23307864

Computer Aided Design in Engineering Education.

ERIC Educational Resources Information Center

Gobin, R.

1986-01-01

Discusses the use of Computer Aided Design (CAD) and Computer Aided Manufacturing (CAM) systems in an undergraduate engineering education program. Provides a rationale for CAD/CAM use in the already existing engineering program. Describes the methods used in choosing the systems, some initial results, and warnings for first-time users. (TW)

Prosthetic rehabilitation with an implant-supported fixed prosthesis using computer-aided design and computer-aided manufacturing dental technology for a patient with a mandibulectomy: A clinical report.

PubMed

Yoon, Hyung-In; Han, Jung-Suk

2016-02-01

The fabrication of dental prostheses with computer-aided design and computer-aided manufacturing shows acceptable marginal fits and favorable treatment outcomes. This clinical report describes the management of a patient who had undergone a mandibulectomy and received an implant-supported fixed prosthesis by using additive manufacturing for the framework and subtractive manufacturing for the monolithic zirconia restorations. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

The evolving HIV/AIDS response and the urgent tasks ahead.

PubMed

Bertozzi, Stefano M; Martz, Tyler E; Piot, Peter

2009-01-01

AIDS continues to outpace the science, financing, prevention, and treatment efforts of the past quarter-century. There have been different epochs along the evolutionary timeline of the global AIDS response, from the discovery of HIV to the threat posed by the current economic crisis. This timeline serves as a reference to how we have arrived where we are today, in the hope that understanding our past will help us set the course for a more efficient and effective future response.

25 Years of HIV/AIDS: a dermatologist epidemic watcher's perspective.

PubMed

Colven, Roy

2006-10-01

Though history will mark June 1981 as the birthday of the AIDS pandemic, the first true case of the syndrome and its cause originated years before in West-Central Africa. History also highlights the irony that the discovery of AIDS, the detection of its cause, and the development of drugs for its treatment, all occurred far from its origin, and now, 25 years later, the greatest burden of this disease is where it is believed to have started.

Computers in Manufacturing.

ERIC Educational Resources Information Center

Hudson, C. A.

1982-01-01

Advances in factory computerization (computer-aided design and computer-aided manufacturing) are reviewed, including discussions of robotics, human factors engineering, and the sociological impact of automation. (JN)

A novel in silico approach to drug discovery via computational intelligence.

PubMed

Hecht, David; Fogel, Gary B

2009-04-01

A computational intelligence drug discovery platform is introduced as an innovative technology designed to accelerate high-throughput drug screening for generalized protein-targeted drug discovery. This technology results in collections of novel small molecule compounds that bind to protein targets as well as details on predicted binding modes and molecular interactions. The approach was tested on dihydrofolate reductase (DHFR) for novel antimalarial drug discovery; however, the methods developed can be applied broadly in early stage drug discovery and development. For this purpose, an initial fragment library was defined, and an automated fragment assembly algorithm was generated. These were combined with a computational intelligence screening tool for prescreening of compounds relative to DHFR inhibition. The entire method was assayed relative to spaces of known DHFR inhibitors and with chemical feasibility in mind, leading to experimental validation in future studies.

View of the shuttle orbiter Discovery's payload bay during RMS checkout

NASA Image and Video Library

1997-02-12

S82-E-5014 (12 Feb. 1997) --- Space Shuttle Discovery's Remote Manipulator System (RMS) gets a preliminary workout in preparation for a busy work load later in the week. The crewmembers are preparing for a scheduled Extravehicular Activity (EVA) with the Hubble Space Telescope (HST), which will be pulled into the Space Shuttle Discovery's cargo bay with the aid of the Remote Manipulator System (RMS). A series of EVA's will be required to properly service the giant telescope. This view was taken with an Electronic Still Camera (ESC).

Novel opportunities for computational biology and sociology in drug discovery☆

PubMed Central

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

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

PubMed

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.

The Effects of Computer-Aided Design Software on Engineering Students' Spatial Visualisation Skills

ERIC Educational Resources Information Center

Kösa, Temel; Karakus, Fatih

2018-01-01

The purpose of this study was to determine the influence of computer-aided design (CAD) software-based instruction on the spatial visualisation skills of freshman engineering students in a computer-aided engineering drawing course. A quasi-experimental design was applied, using the Purdue Spatial Visualization Test-Visualization of Rotations…

Teaching Computer-Aided Design of Fluid Flow and Heat Transfer Engineering Equipment.

ERIC Educational Resources Information Center

Gosman, A. D.; And Others

1979-01-01

Describes a teaching program for fluid mechanics and heat transfer which contains both computer aided learning (CAL) and computer aided design (CAD) components and argues that the understanding of the physical and numerical modeling taught in the CAL course is essential to the proper implementation of CAD. (Author/CMV)

Computer-Presented Organizational/Memory Aids as Instruction for Solving Pico-Fomi Problems.

ERIC Educational Resources Information Center

Steinberg, Esther R.; And Others

1985-01-01

Describes investigation of effectiveness of computer-presented organizational/memory aids (matrix and verbal charts controlled by computer or learner) as instructional technique for solving Pico-Fomi problems, and the acquisition of deductive inference rules when such aids are present. Results indicate chart use control should be adapted to…

Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation

PubMed Central

Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.

2016-01-01

Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709

S-MART, a software toolbox to aid RNA-Seq data analysis.

PubMed

Zytnicki, Matthias; Quesneville, Hadi

2011-01-01

High-throughput sequencing is now routinely performed in many experiments. But the analysis of the millions of sequences generated, is often beyond the expertise of the wet labs who have no personnel specializing in bioinformatics. Whereas several tools are now available to map high-throughput sequencing data on a genome, few of these can extract biological knowledge from the mapped reads. We have developed a toolbox called S-MART, which handles mapped RNA-Seq data. S-MART is an intuitive and lightweight tool which performs many of the tasks usually required for the analysis of mapped RNA-Seq reads. S-MART does not require any computer science background and thus can be used by all of the biologist community through a graphical interface. S-MART can run on any personal computer, yielding results within an hour even for Gb of data for most queries. S-MART may perform the entire analysis of the mapped reads, without any need for other ad hoc scripts. With this tool, biologists can easily perform most of the analyses on their computer for their RNA-Seq data, from the mapped data to the discovery of important loci.

S-MART, A Software Toolbox to Aid RNA-seq Data Analysis

PubMed Central

Zytnicki, Matthias; Quesneville, Hadi

2011-01-01

High-throughput sequencing is now routinely performed in many experiments. But the analysis of the millions of sequences generated, is often beyond the expertise of the wet labs who have no personnel specializing in bioinformatics. Whereas several tools are now available to map high-throughput sequencing data on a genome, few of these can extract biological knowledge from the mapped reads. We have developed a toolbox called S-MART, which handles mapped RNA-Seq data. S-MART is an intuitive and lightweight tool which performs many of the tasks usually required for the analysis of mapped RNA-Seq reads. S-MART does not require any computer science background and thus can be used by all of the biologist community through a graphical interface. S-MART can run on any personal computer, yielding results within an hour even for Gb of data for most queries. S-MART may perform the entire analysis of the mapped reads, without any need for other ad hoc scripts. With this tool, biologists can easily perform most of the analyses on their computer for their RNA-Seq data, from the mapped data to the discovery of important loci. PMID:21998740

Addressing the coming radiology crisis-the Society for Computer Applications in Radiology transforming the radiological interpretation process (TRIP) initiative.

PubMed

Andriole, Katherine P; Morin, Richard L; Arenson, Ronald L; Carrino, John A; Erickson, Bradley J; Horii, Steven C; Piraino, David W; Reiner, Bruce I; Seibert, J Anthony; Siegel, Eliot

2004-12-01

The Society for Computer Applications in Radiology (SCAR) Transforming the Radiological Interpretation Process (TRIP) Initiative aims to spearhead research, education, and discovery of innovative solutions to address the problem of information and image data overload. The initiative will foster interdisciplinary research on technological, environmental and human factors to better manage and exploit the massive amounts of data. TRIP will focus on the following basic objectives: improving the efficiency of interpretation of large data sets, improving the timeliness and effectiveness of communication, and decreasing medical errors. The ultimate goal of the initiative is to improve the quality and safety of patient care. Interdisciplinary research into several broad areas will be necessary to make progress in managing the ever-increasing volume of data. The six concepts involved are human perception, image processing and computer-aided detection (CAD), visualization, navigation and usability, databases and integration, and evaluation and validation of methods and performance. The result of this transformation will affect several key processes in radiology, including image interpretation; communication of imaging results; workflow and efficiency within the health care enterprise; diagnostic accuracy and a reduction in medical errors; and, ultimately, the overall quality of care.

Benchmarking Ligand-Based Virtual High-Throughput Screening with the PubChem Database

PubMed Central

Butkiewicz, Mariusz; Lowe, Edward W.; Mueller, Ralf; Mendenhall, Jeffrey L.; Teixeira, Pedro L.; Weaver, C. David; Meiler, Jens

2013-01-01

With the rapidly increasing availability of High-Throughput Screening (HTS) data in the public domain, such as the PubChem database, methods for ligand-based computer-aided drug discovery (LB-CADD) have the potential to accelerate and reduce the cost of probe development and drug discovery efforts in academia. We assemble nine data sets from realistic HTS campaigns representing major families of drug target proteins for benchmarking LB-CADD methods. Each data set is public domain through PubChem and carefully collated through confirmation screens validating active compounds. These data sets provide the foundation for benchmarking a new cheminformatics framework BCL::ChemInfo, which is freely available for non-commercial use. Quantitative structure activity relationship (QSAR) models are built using Artificial Neural Networks (ANNs), Support Vector Machines (SVMs), Decision Trees (DTs), and Kohonen networks (KNs). Problem-specific descriptor optimization protocols are assessed including Sequential Feature Forward Selection (SFFS) and various information content measures. Measures of predictive power and confidence are evaluated through cross-validation, and a consensus prediction scheme is tested that combines orthogonal machine learning algorithms into a single predictor. Enrichments ranging from 15 to 101 for a TPR cutoff of 25% are observed. PMID:23299552

Stabilized helical peptides: overview of the technologies and its impact on drug discovery.

PubMed

Klein, Mark

2017-11-01

Protein-protein interactions are predominant in the workings of all cells. Until now, there have been a few successes in targeting protein-protein interactions with small molecules. Peptides may overcome some of the challenges of small molecules in disrupting protein-protein interactions. However, peptides present a new set of challenges in drug discovery. Thus, the study of the stabilization of helical peptides has been extensive. Areas covered: Several technological approaches to helical peptide stabilization have been studied. In this review, stapled peptides, foldamers, and hydrogen bond surrogates are discussed. Issues regarding design principles are also discussed. Furthermore, this review introduces select computational techniques used to aid peptide design and discusses clinical trials of peptides in a more advanced stage of development. Expert opinion: Stabilized helical peptides hold great promise in a wide array of diseases. However, the field is still relatively new and new design principles are emerging. The possibilities of peptide modification are quite extensive and expanding, so the design of stabilized peptides requires great attention to detail in order to avoid a large number of failed lead peptides. The start of clinical trials with stapled peptides is a promising sign for the future.

Enabling drug discovery project decisions with integrated computational chemistry and informatics

NASA Astrophysics Data System (ADS)

Tsui, Vickie; Ortwine, Daniel F.; Blaney, Jeffrey M.

2017-03-01

Computational chemistry/informatics scientists and software engineers in Genentech Small Molecule Drug Discovery collaborate with experimental scientists in a therapeutic project-centric environment. Our mission is to enable and improve pre-clinical drug discovery design and decisions. Our goal is to deliver timely data, analysis, and modeling to our therapeutic project teams using best-in-class software tools. We describe our strategy, the organization of our group, and our approaches to reach this goal. We conclude with a summary of the interdisciplinary skills required for computational scientists and recommendations for their training.

IDENTIFYING TOXIC LEADERSHIP BEHAVIORS AND TOOLS TO FACILITATE THEIR DISCOVERY

DTIC Science & Technology

2016-01-31

AIR WAR COLLEGE AIR UNIVERSITY IDENTIFYING TOXIC LEADERSHIP BEHAVIORS AND TOOLS TO FACILITATE THEIR DISCOVERY by Michael Boger, Lt Col...released investigations for specific, observable traits relating to toxic behavior . 3) Discuss indicators and concerns in steps one and two with...subordinates, which will aid in validating the specific observable behaviors from the lenses of each of these positions. The application of their input

Computer-aided design development transition for IPAD environment

NASA Technical Reports Server (NTRS)

Owens, H. G.; Mock, W. D.; Mitchell, J. C.

1980-01-01

The relationship of federally sponsored computer-aided design/computer-aided manufacturing (CAD/CAM) programs to the aircraft life cycle design process, an overview of NAAD'S CAD development program, an evaluation of the CAD design process, a discussion of the current computing environment within which NAAD is developing its CAD system, some of the advantages/disadvantages of the NAAD-IPAD approach, and CAD developments during transition into the IPAD system are discussed.

CAD/CAE Integration Enhanced by New CAD Services Standard

NASA Technical Reports Server (NTRS)

Claus, Russell W.

2002-01-01

A Government-industry team led by the NASA Glenn Research Center has developed a computer interface standard for accessing data from computer-aided design (CAD) systems. The Object Management Group, an international computer standards organization, has adopted this CAD services standard. The new standard allows software (e.g., computer-aided engineering (CAE) and computer-aided manufacturing software to access multiple CAD systems through one programming interface. The interface is built on top of a distributed computing system called the Common Object Request Broker Architecture (CORBA). CORBA allows the CAD services software to operate in a distributed, heterogeneous computing environment.

Investigations in Computer-Aided Instruction and Computer-Aided Controls. Final Report.

ERIC Educational Resources Information Center

Rosenberg, R.C.; And Others

These research projects, designed to delve into certain relationships between humans and computers, are focused on computer-assisted instruction and on man-computer interaction. One study demonstrates that within the limits of formal engineering theory, a computer simulated laboratory (Dynamic Systems Laboratory) can be built in which freshmen…

Computer Numerical Control: Instructional Manual. The North Dakota High Technology Mobile Laboratory Project.

ERIC Educational Resources Information Center

Sinn, John W.

This instructional manual contains five learning activity packets for use in a workshop on computer numerical control for computer-aided manufacturing. The lessons cover the following topics: introduction to computer-aided manufacturing, understanding the lathe, using the computer, computer numerically controlled part programming, and executing a…

[Key points for esthetic rehabilitation of anterior teeth using chair-side computer aided design and computer aided manufacture technique].

PubMed

Yang, J; Feng, H L

2018-04-09

With the rapid development of the chair-side computer aided design and computer aided manufacture (CAD/CAM) technology, its accuracy and operability of have been greatly improved in recent years. Chair-side CAD/CAM system may produce all kinds of indirect restorations, and has the advantages of rapid, accurate and stable production. It has become the future development direction of Stomatology. This paper describes the clinical application of the chair-side CAD/CAM technology for anterior aesthetic restorations from the aspects of shade and shape.

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

PubMed

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.

A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

PubMed

Li, Qian; Li, Xudong; Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-03-22

Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking.

A Network-Based Multi-Target Computational Estimation Scheme for Anticoagulant Activities of Compounds

PubMed Central

Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-01-01

Background Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. Methodology We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. Conclusions This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking. PMID:21445339

A resource management architecture based on complex network theory in cloud computing federation

NASA Astrophysics Data System (ADS)

Zhang, Zehua; Zhang, Xuejie

2011-10-01

Cloud Computing Federation is a main trend of Cloud Computing. Resource Management has significant effect on the design, realization, and efficiency of Cloud Computing Federation. Cloud Computing Federation has the typical characteristic of the Complex System, therefore, we propose a resource management architecture based on complex network theory for Cloud Computing Federation (abbreviated as RMABC) in this paper, with the detailed design of the resource discovery and resource announcement mechanisms. Compare with the existing resource management mechanisms in distributed computing systems, a Task Manager in RMABC can use the historical information and current state data get from other Task Managers for the evolution of the complex network which is composed of Task Managers, thus has the advantages in resource discovery speed, fault tolerance and adaptive ability. The result of the model experiment confirmed the advantage of RMABC in resource discovery performance.

A Perspective on the Role of Computational Models in Immunology.

PubMed

Chakraborty, Arup K

2017-04-26

This is an exciting time for immunology because the future promises to be replete with exciting new discoveries that can be translated to improve health and treat disease in novel ways. Immunologists are attempting to answer increasingly complex questions concerning phenomena that range from the genetic, molecular, and cellular scales to that of organs, whole animals or humans, and populations of humans and pathogens. An important goal is to understand how the many different components involved interact with each other within and across these scales for immune responses to emerge, and how aberrant regulation of these processes causes disease. To aid this quest, large amounts of data can be collected using high-throughput instrumentation. The nonlinear, cooperative, and stochastic character of the interactions between components of the immune system as well as the overwhelming amounts of data can make it difficult to intuit patterns in the data or a mechanistic understanding of the phenomena being studied. Computational models are increasingly important in confronting and overcoming these challenges. I first describe an iterative paradigm of research that integrates laboratory experiments, clinical data, computational inference, and mechanistic computational models. I then illustrate this paradigm with a few examples from the recent literature that make vivid the power of bringing together diverse types of computational models with experimental and clinical studies to fruitfully interrogate the immune system.

Strategies for the Creation, Design and Implementation of Effective Interactive Computer-Aided Learning Software in Numerate Business Subjects--The Byzantium Experience.

ERIC Educational Resources Information Center

Wilkinson-Riddle, G. J.; Patel, Ashok

1998-01-01

Discusses courseware development, including intelligent tutoring systems, under the Teaching and Learning Technology Programme and the Byzantium project that was designed to define computer-aided learning performance standards suitable for numerate business subjects; examine reasons to use computer-aided learning; and improve access to educational…

Enhancing Engineering Computer-Aided Design Education Using Lectures Recorded on the PC

ERIC Educational Resources Information Center

McGrann, Roy T. R.

2006-01-01

Computer-Aided Engineering (CAE) is a course that is required during the third year in the mechanical engineering curriculum at Binghamton University. The primary objective of the course is to educate students in the procedures of computer-aided engineering design. The solid modeling and analysis program Pro/Engineer[TM] (PTC[R]) is used as the…

Key Issues in Instructional Computer Graphics.

ERIC Educational Resources Information Center

Wozny, Michael J.

1981-01-01

Addresses key issues facing universities which plan to establish instructional computer graphics facilities, including computer-aided design/computer aided manufacturing systems, role in curriculum, hardware, software, writing instructional software, faculty involvement, operations, and research. Thirty-seven references and two appendices are…

Computer Programming Languages and Expertise Needed by Practicing Engineers.

ERIC Educational Resources Information Center

Doelling, Irvin

1980-01-01

Discussed is the present engineering computer environment of a large aerospace company recognized as a leader in the application and development of computer-aided design and computer-aided manufacturing techniques. A review is given of the exposure spectrum of engineers to the world of computing, the computer languages used, and the career impacts…

Computer-aided detection systems to improve lung cancer early diagnosis: state-of-the-art and challenges

NASA Astrophysics Data System (ADS)

Traverso, A.; Lopez Torres, E.; Fantacci, M. E.; Cerello, P.

2017-05-01

Lung cancer is one of the most lethal types of cancer, because its early diagnosis is not good enough. In fact, the detection of pulmonary nodule, potential lung cancers, in Computed Tomography scans is a very challenging and time-consuming task for radiologists. To support radiologists, researchers have developed Computer-Aided Diagnosis (CAD) systems for the automated detection of pulmonary nodules in chest Computed Tomography scans. Despite the high level of technological developments and the proved benefits on the overall detection performance, the usage of Computer-Aided Diagnosis in clinical practice is far from being a common procedure. In this paper we investigate the causes underlying this discrepancy and present a solution to tackle it: the M5L WEB- and Cloud-based on-demand Computer-Aided Diagnosis. In addition, we prove how the combination of traditional imaging processing techniques with state-of-art advanced classification algorithms allows to build a system whose performance could be much larger than any Computer-Aided Diagnosis developed so far. This outcome opens the possibility to use the CAD as clinical decision support for radiologists.

Nexus Between Protein–Ligand Affinity Rank-Ordering, Biophysical Approaches, and Drug Discovery

PubMed Central

2013-01-01

The confluence of computational and biophysical methods to accurately rank-order the binding affinities of small molecules and determine structures of macromolecular complexes is a potentially transformative advance in the work flow of drug discovery. This viewpoint explores the impact that advanced computational methods may have on the efficacy of small molecule drug discovery and optimization, particularly with respect to emerging fragment-based methods. PMID:24900579

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

ERIC Educational Resources Information Center

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…

Symposium on Biomedical Applications of Basic Research Held in Woods Hole, Massachusetts on 15 August 1988.

DTIC Science & Technology

1989-02-10

to the AIDS virus , in a presentation titled "Marine Invertebrate Immunity: The AIDS Cqnnectlon." Funding for "Biomedical Applications of Basic...ibl itY Codes iAv ~li anti/or Dist. Spoc al The February evening in 1975 after MV Islander hit the Gould are Alan G. Lunn, left, marine contractor...discovery 25 years ago in the mtnt, Dr. Kornberg pointed out. is that the AIDS virus is covea, they are abundant only where laboratory of Frederik B

A review of computer-aided oral and maxillofacial surgery: planning, simulation and navigation.

PubMed

Chen, Xiaojun; Xu, Lu; Sun, Yi; Politis, Constantinus

2016-11-01

Currently, oral and maxillofacial surgery (OMFS) still poses a significant challenge for surgeons due to the anatomic complexity and limited field of view of the oral cavity. With the great development of computer technologies, he computer-aided surgery has been widely used for minimizing the risks and improving the precision of surgery. Areas covered: The major goal of this paper is to provide a comprehensive reference source of current and future development of computer-aided OMFS including surgical planning, simulation and navigation for relevant researchers. Expert commentary: Compared with the traditional OMFS, computer-aided OMFS overcomes the disadvantage that the treatment on the region of anatomically complex maxillofacial depends almost exclusively on the experience of the surgeon.

Software For Computer-Aided Design Of Control Systems

NASA Technical Reports Server (NTRS)

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.

NREL Kicks Off Next Phase of Advanced Computer-Aided Battery Engineering |

Science.gov Websites

lithium-ion (Li-ion) batteries, known as a multi-scale multi-domain (GH-MSMD) model framework, was News | NREL Kicks Off Next Phase of Advanced Computer-Aided Battery Engineering NREL Kicks Off Next Phase of Advanced Computer-Aided Battery Engineering March 16, 2016 NREL researcher looks across

Defense Acquisitions Acronyms and Terms

DTIC Science & Technology

2012-12-01

Computer-Aided Design CADD Computer-Aided Design and Drafting CAE Component Acquisition Executive; Computer-Aided Engineering CAIV Cost As an...Radiation to Ordnance HFE Human Factors Engineering HHA Health Hazard Assessment HNA Host-Nation Approval HNS Host-Nation Support HOL High -Order...Engineering Change Proposal VHSIC Very High Speed Integrated Circuit VLSI Very Large Scale Integration VOC Volatile Organic Compound W WAN Wide

[The automatic iris map overlap technology in computer-aided iridiagnosis].

PubMed

He, Jia-feng; Ye, Hu-nian; Ye, Miao-yuan

2002-11-01

In the paper, iridology and computer-aided iridiagnosis technologies are briefly introduced and the extraction method of the collarette contour is then investigated. The iris map can be overlapped on the original iris image based on collarette contour extraction. The research on collarette contour extraction and iris map overlap is of great importance to computer-aided iridiagnosis technologies.

New Paradigms for Computer Aids to Invention.

ERIC Educational Resources Information Center

Langston, M. Diane

Many people are interested in computer aids to rhetorical invention and want to know how to evaluate an invention aid, what the criteria are for a good one, and how to assess the trade-offs involved in buying one product or another. The frame of reference for this evaluation is an "old paradigm," which treats the computer as if it were…

Multimedia Image Technology and Computer Aided Manufacturing Engineering Analysis

NASA Astrophysics Data System (ADS)

Nan, Song

2018-03-01

Since the reform and opening up, with the continuous development of science and technology in China, more and more advanced science and technology have emerged under the trend of diversification. Multimedia imaging technology, for example, has a significant and positive impact on computer aided manufacturing engineering in China. From the perspective of scientific and technological advancement and development, the multimedia image technology has a very positive influence on the application and development of computer-aided manufacturing engineering, whether in function or function play. Therefore, this paper mainly starts from the concept of multimedia image technology to analyze the application of multimedia image technology in computer aided manufacturing engineering.

Astrobiology, space and the future age of discovery.

PubMed

Blumberg, Baruch S

2011-02-13

Astrobiology is the study of the origins, evolution, distribution and future of life in the Universe, and specifically seeks to understand the origin of life and to test the hypothesis that life exists elsewhere than on Earth. There is a general mathematics, physics and chemistry; that is, scientific laws that obtain on Earth also do so elsewhere. Is there a general biology? Is the Universe life-rich or is Earth an isolated island of biology? Exploration in the Age of Enlightenment required the collection of data in unexplored regions and the use of induction and empiricism to derive models and natural laws. The current search for extra-terrestrial life has a similar goal, but with a much greater amount of data and with computers to help with management, correlations, pattern recognition and analysis. There are 60 active space missions, many of them aiding in the search for life. There is not a universally accepted definition of life, but there are a series of characteristics that can aid in the identification of life elsewhere. The study of locations on Earth with similarities to early Mars and other space objects could provide a model that can be used in the search for extra-terrestrial life.

Three-Dimensional Computational Fluid Dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haworth, D.C.; O'Rourke, P.J.; Ranganathan, R.

1998-09-01

Computational fluid dynamics (CFD) is one discipline falling under the broad heading of computer-aided engineering (CAE). CAE, together with computer-aided design (CAD) and computer-aided manufacturing (CAM), comprise a mathematical-based approach to engineering product and process design, analysis and fabrication. In this overview of CFD for the design engineer, our purposes are three-fold: (1) to define the scope of CFD and motivate its utility for engineering, (2) to provide a basic technical foundation for CFD, and (3) to convey how CFD is incorporated into engineering product and process design.

Teach-Discover-Treat (TDT): Collaborative Computational Drug Discovery for Neglected Diseases

PubMed Central

Jansen, Johanna M.; Cornell, Wendy; Tseng, Y. Jane; Amaro, Rommie E.

2012-01-01

Teach – Discover – Treat (TDT) is an initiative to promote the development and sharing of computational tools solicited through a competition with the aim to impact education and collaborative drug discovery for neglected diseases. Collaboration, multidisciplinary integration, and innovation are essential for successful drug discovery. This requires a workforce that is trained in state-of-the-art workflows and equipped with the ability to collaborate on platforms that are accessible and free. The TDT competition solicits high quality computational workflows for neglected disease targets, using freely available, open access tools. PMID:23085175

Computer Aided Manufacturing.

ERIC Educational Resources Information Center

Insolia, Gerard

This document contains course outlines in computer-aided manufacturing developed for a business-industry technology resource center for firms in eastern Pennsylvania by Northampton Community College. The four units of the course cover the following: (1) introduction to computer-assisted design (CAD)/computer-assisted manufacturing (CAM); (2) CAM…

Buying CAM.

ERIC Educational Resources Information Center

Meloy, Jim; And Others

1990-01-01

The relationship between computer-aided design (CAD), computer-aided manufacturing (CAM), and computer numerical control (CNC) computer applications is described. Tips for helping educate the CAM buyer on what to look for and what to avoid when searching for the most appropriate instructional CAM package are provided. (KR)

Computer-Aided Design and Computer-Aided Manufacturing Hydroxyapatite/Epoxide Acrylate Maleic Compound Construction for Craniomaxillofacial Bone Defects.

PubMed

Zhang, Lei; Shen, Shunyao; Yu, Hongbo; Shen, Steve Guofang; Wang, Xudong

2015-07-01

The aim of this study was to investigate the use of computer-aided design and computer-aided manufacturing hydroxyapatite (HA)/epoxide acrylate maleic (EAM) compound construction artificial implants for craniomaxillofacial bone defects. Computed tomography, computer-aided design/computer-aided manufacturing and three-dimensional reconstruction, as well as rapid prototyping were performed in 12 patients between 2008 and 2013. The customized HA/EAM compound artificial implants were manufactured through selective laser sintering using a rapid prototyping machine into the exact geometric shapes of the defect. The HA/EAM compound artificial implants were then implanted during surgical reconstruction. Color-coded superimpositions demonstrated the discrepancy between the virtual plan and achieved results using Geomagic Studio. As a result, the HA/EAM compound artificial bone implants were perfectly matched with the facial areas that needed reconstruction. The postoperative aesthetic and functional results were satisfactory. The color-coded superimpositions demonstrated good consistency between the virtual plan and achieved results. The three-dimensional maximum deviation is 2.12 ± 0.65  mm and the three-dimensional mean deviation is 0.27 ± 0.07  mm. No facial nerve weakness or pain was observed at the follow-up examinations. Only 1 implant had to be removed 2 months after the surgery owing to severe local infection. No other complication was noted during the follow-up period. In conclusion, computer-aided, individually fabricated HA/EAM compound construction artificial implant was a good craniomaxillofacial surgical technique that yielded improved aesthetic results and functional recovery after reconstruction.

Accuracy evaluation of metal copings fabricated by computer-aided milling and direct metal laser sintering systems

PubMed Central

Lee, Wan-Sun; Kim, Woong-Chul

2015-01-01

PURPOSE To assess the marginal and internal gaps of the copings fabricated by computer-aided milling and direct metal laser sintering (DMLS) systems in comparison to casting method. MATERIALS AND METHODS Ten metal copings were fabricated by casting, computer-aided milling, and DMLS. Seven mesiodistal and labiolingual positions were then measured, and each of these were divided into the categories; marginal gap (MG), cervical gap (CG), axial wall at internal gap (AG), and incisal edge at internal gap (IG). Evaluation was performed by a silicone replica technique. A digital microscope was used for measurement of silicone layer. Statistical analyses included one-way and repeated measure ANOVA to test the difference between the fabrication methods and categories of measured points (α=.05), respectively. RESULTS The mean gap differed significantly with fabrication methods (P<.001). Casting produced the narrowest gap in each of the four measured positions, whereas CG, AG, and IG proved narrower in computer-aided milling than in DMLS. Thus, with the exception of MG, all positions exhibited a significant difference between computer-aided milling and DMLS (P<.05). CONCLUSION Although the gap was found to vary with fabrication methods, the marginal and internal gaps of the copings fabricated by computer-aided milling and DMLS fell within the range of clinical acceptance (<120 µm). However, the statistically significant difference to conventional casting indicates that the gaps in computer-aided milling and DMLS fabricated restorations still need to be further reduced. PMID:25932310

Accuracy evaluation of metal copings fabricated by computer-aided milling and direct metal laser sintering systems.

PubMed

Park, Jong-Kyoung; Lee, Wan-Sun; Kim, Hae-Young; Kim, Woong-Chul; Kim, Ji-Hwan

2015-04-01

To assess the marginal and internal gaps of the copings fabricated by computer-aided milling and direct metal laser sintering (DMLS) systems in comparison to casting method. Ten metal copings were fabricated by casting, computer-aided milling, and DMLS. Seven mesiodistal and labiolingual positions were then measured, and each of these were divided into the categories; marginal gap (MG), cervical gap (CG), axial wall at internal gap (AG), and incisal edge at internal gap (IG). Evaluation was performed by a silicone replica technique. A digital microscope was used for measurement of silicone layer. Statistical analyses included one-way and repeated measure ANOVA to test the difference between the fabrication methods and categories of measured points (α=.05), respectively. The mean gap differed significantly with fabrication methods (P<.001). Casting produced the narrowest gap in each of the four measured positions, whereas CG, AG, and IG proved narrower in computer-aided milling than in DMLS. Thus, with the exception of MG, all positions exhibited a significant difference between computer-aided milling and DMLS (P<.05). Although the gap was found to vary with fabrication methods, the marginal and internal gaps of the copings fabricated by computer-aided milling and DMLS fell within the range of clinical acceptance (<120 µm). However, the statistically significant difference to conventional casting indicates that the gaps in computer-aided milling and DMLS fabricated restorations still need to be further reduced.

Content-Based Discovery for Web Map Service using Support Vector Machine and User Relevance Feedback

PubMed Central

Cheng, Xiaoqiang; Qi, Kunlun; Zheng, Jie; You, Lan; Wu, Huayi

2016-01-01

Many discovery methods for geographic information services have been proposed. There are approaches for finding and matching geographic information services, methods for constructing geographic information service classification schemes, and automatic geographic information discovery. Overall, the efficiency of the geographic information discovery keeps improving., There are however, still two problems in Web Map Service (WMS) discovery that must be solved. Mismatches between the graphic contents of a WMS and the semantic descriptions in the metadata make discovery difficult for human users. End-users and computers comprehend WMSs differently creating semantic gaps in human-computer interactions. To address these problems, we propose an improved query process for WMSs based on the graphic contents of WMS layers, combining Support Vector Machine (SVM) and user relevance feedback. Our experiments demonstrate that the proposed method can improve the accuracy and efficiency of WMS discovery. PMID:27861505

Content-Based Discovery for Web Map Service using Support Vector Machine and User Relevance Feedback.

PubMed

Hu, Kai; Gui, Zhipeng; Cheng, Xiaoqiang; Qi, Kunlun; Zheng, Jie; You, Lan; Wu, Huayi

2016-01-01

Many discovery methods for geographic information services have been proposed. There are approaches for finding and matching geographic information services, methods for constructing geographic information service classification schemes, and automatic geographic information discovery. Overall, the efficiency of the geographic information discovery keeps improving., There are however, still two problems in Web Map Service (WMS) discovery that must be solved. Mismatches between the graphic contents of a WMS and the semantic descriptions in the metadata make discovery difficult for human users. End-users and computers comprehend WMSs differently creating semantic gaps in human-computer interactions. To address these problems, we propose an improved query process for WMSs based on the graphic contents of WMS layers, combining Support Vector Machine (SVM) and user relevance feedback. Our experiments demonstrate that the proposed method can improve the accuracy and efficiency of WMS discovery.

The changing features of the body-mind problem.

PubMed

Agassi, Joseph

2007-01-01

The body-mind problem invites scientific study, since mental events are repeated and repeatable and invite testable explanations. They seemed troublesome because of the classical theory of substance that failed to solve its own central problems. These are soluble with the aid of the theory of the laws of nature, particularly in its emergentist version [Bunge, M., 1980. The Body-mind Problem, Pergamon, Oxford] that invites refutable explanations [Popper, K.R., 1959. The Logic of Scientific Discovery, Hutchinson, London]. The view of mental properties as emergent is a modification of the two chief classical views, materialism and dualism. As this view invites testable explanations of events of the inner world, it is better than the quasi-behaviorist view of self-awareness as computer-style self-monitoring [Minsky, M., Laske, O., 1992. A conversation with Marvin Minsky. AI Magazine 13 (3), 31-45].

CADD Modeling of Multi-Target Drugs Against Alzheimer's Disease.

PubMed

Ambure, Pravin; Roy, Kunal

2017-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder that is described by multiple factors linked with the progression of the disease. The currently approved drugs in the market are not capable of curing AD; instead, they merely provide symptomatic relief. Development of multi-target directed ligands (MTDLs) is an emerging strategy for improving the quality of the treatment against complex diseases like AD. Polypharmacology is a branch of pharmaceutical sciences that deals with the MTDL development. In this mini-review, we have summarized and discussed different strategies that are reported in the literature to design MTDLs for AD. Further, we have discussed the role of different in silico techniques and online resources in computer-aided drug discovery (CADD), for designing or identifying MTDLs against AD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Data Farming and Defense Applications

NASA Technical Reports Server (NTRS)

Horne, Gary; Meyer, Ted

2011-01-01

.Data farm,ing uses simulation modeling, high performance computing, experimental design and analysis to examine questions of interest with large possibility spaces. This methodology allows for the examination of whole landscapes of potential outcomes and provides the capability of executing enough experiments so that outliers might be captured and examined for insights. It can be used to conduct sensitivity studies, to support validation and verification of models, to iteratively optimize outputs using heuristic search and discovery, and as an aid to decision-makers in understanding complex relationships of factors. In this paper we describe efforts at the Naval Postgraduate School in developing these new and emerging tools. We also discuss data farming in the context of application to questions inherent in military decision-making. The particular application we illustrate here is social network modeling to support the countering of improvised explosive devices.

Support for Learning with Computer Simulations: Giving Hints, Supporting Learning Processes, and Providing Hypotheses.

ERIC Educational Resources Information Center

Njoo, Melanie; de Jong, Ton

This paper contains the results of a study on the importance of discovery learning using computer simulations. The purpose of the study was to identify what constitutes discovery learning and to assess the effects of instructional support measures. College students were observed working with an assignment and a computer simulation in the domain of…

Computationally driven drug discovery meeting-3 - Verona (Italy): 4 - 6th of March 2014.

PubMed

Costantino, Gabriele

2014-12-01

The following article reports on the results and the outcome of a meeting organised at the Aptuit Auditorium in Verona (Italy), which highlighted the current applications of state-of-the-art computational science to drug design in Italy. The meeting, which had > 100 people in attendance, consisted of over 40 presentations and included keynote lectures given by world-renowned speakers. The topics included in the meeting are areas related to ligand and structure-based ligand design and library design and screening; it also provided discussion pertaining to chemometrics. The meeting also stressed the importance of public-private collaboration and reviewed the different approaches to computationally driven drug discovery taken within academia and industry. The meeting helped define the current position of state-of-the-art computational drug discovery in Italy, pointing out criticalities and assets. This kind of focused meeting is important in the sense that it lends the opportunity of a restricted yet representative community of fellow professionals to deeply discuss the current methodological approaches and provide future perspectives for computationally driven drug discovery.

Discovery Systems

NASA Technical Reports Server (NTRS)

Pell, Barney

2003-01-01

A viewgraph presentation on NASA's Discovery Systems Project is given. The topics of discussion include: 1) NASA's Computing Information and Communications Technology Program; 2) Discovery Systems Program; and 3) Ideas for Information Integration Using the Web.

A Review of Developments in Computer-Based Systems to Image Teeth and Produce Dental Restorations

PubMed Central

Rekow, E. Dianne; Erdman, Arthur G.; Speidel, T. Michael

1987-01-01

Computer-aided design and manufacturing (CAD/CAM) make it possible to automate the creation of dental restorations. Currently practiced techniques are described. Three automated systems currently under development are described and compared. Advances in computer-aided design and computer-aided manufacturing (CAD/CAM) provide a new option for dentistry, creating an alternative technique for producing dental restorations. It is possible to create dental restorations that are automatically produced and meet or exceed current requirements for fit and occlusion.

Photogrammetry and computer-aided piping design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keneflick, J.F.; Chirillo, R.D.

1985-02-18

Three-dimensional measurements taken from photographs of a plant model can be digitized and linked with computer-aided piping design. This can short-cut the design and construction of new plants and expedite repair and retrofitting projects. Some designers bridge the gap between model and computer by digitizing from orthographic prints obtained via orthography or the laser scanning of model sections. Such valve or fitting then processed is described in this paper. The marriage of photogrammetry and computer-aided piping design can economically produce such numerical drawings.

Integration of the Execution Support System for the Computer-Aided Prototyping System (CAPS)

DTIC Science & Technology

1990-09-01

SUPPORT SYSTEM FOR THE COMPUTER -AIDED PROTOTYPING SYSTEM (CAPS) by Frank V. Palazzo September 1990 Thesis Advisor: Luq± Approved for public release...ZATON REPOR ,,.VBE (, 6a NAME OF PERPORMING ORGAN ZAT7ON 6b OFF:CE SYVBOL 7a NAME OF MONITORINC O0-CA’Za- ON Computer Science Department (if applicable...Include Security Classification) Integration of the Execution Support System for the Computer -Aided Prototyping System (C S) 12 PERSONAL AUTHOR(S) Frank V

Influence of Computer-Aided Detection on Performance of Screening Mammography

PubMed Central

Fenton, Joshua J.; Taplin, Stephen H.; Carney, Patricia A.; Abraham, Linn; Sickles, Edward A.; D'Orsi, Carl; Berns, Eric A.; Cutter, Gary; Hendrick, R. Edward; Barlow, William E.; Elmore, Joann G.

2011-01-01

Background Computer-aided detection identifies suspicious findings on mammograms to assist radiologists. Since the Food and Drug Administration approved the technology in 1998, it has been disseminated into practice, but its effect on the accuracy of interpretation is unclear. Methods We determined the association between the use of computer-aided detection at mammography facilities and the performance of screening mammography from 1998 through 2002 at 43 facilities in three states. We had complete data for 222,135 women (a total of 429,345 mammograms), including 2351 women who received a diagnosis of breast cancer within 1 year after screening. We calculated the specificity, sensitivity, and positive predictive value of screening mammography with and without computer-aided detection, as well as the rates of biopsy and breast-cancer detection and the overall accuracy, measured as the area under the receiver-operating-characteristic (ROC) curve. Results Seven facilities (16%) implemented computer-aided detection during the study period. Diagnostic specificity decreased from 90.2% before implementation to 87.2% after implementation (P<0.001), the positive predictive value decreased from 4.1% to 3.2% (P = 0.01), and the rate of biopsy increased by 19.7% (P<0.001). The increase in sensitivity from 80.4% before implementation of computer-aided detection to 84.0% after implementation was not significant (P = 0.32). The change in the cancer-detection rate (including invasive breast cancers and ductal carcinomas in situ) was not significant (4.15 cases per 1000 screening mammograms before implementation and 4.20 cases after implementation, P = 0.90). Analyses of data from all 43 facilities showed that the use of computer-aided detection was associated with significantly lower overall accuracy than was nonuse (area under the ROC curve, 0.871 vs. 0.919; P = 0.005). Conclusions The use of computer-aided detection is associated with reduced accuracy of interpretation of screening mammograms. The increased rate of biopsy with the use of computer-aided detection is not clearly associated with improved detection of invasive breast cancer. PMID:17409321

Discovery of HIV Type 1 Aspartic Protease Hit Compounds through Combined Computational Approaches.

PubMed

Xanthopoulos, Dimitrios; Kritsi, Eftichia; Supuran, Claudiu T; Papadopoulos, Manthos G; Leonis, Georgios; Zoumpoulakis, Panagiotis

2016-08-05

A combination of computational techniques and inhibition assay experiments was employed to identify hit compounds from commercial libraries with enhanced inhibitory potency against HIV type 1 aspartic protease (HIV PR). Extensive virtual screening with the aid of reliable pharmacophore models yielded five candidate protease inhibitors. Subsequent molecular dynamics and molecular mechanics Poisson-Boltzmann surface area free-energy calculations for the five ligand-HIV PR complexes suggested a high stability of the systems through hydrogen-bond interactions between the ligands and the protease's flaps (Ile50/50'), as well as interactions with residues of the active site (Asp25/25'/29/29'/30/30'). Binding-energy calculations for the three most promising compounds yielded values between -5 and -10 kcal mol(-1) and suggested that van der Waals interactions contribute most favorably to the total energy. The predicted binding-energy values were verified by in vitro inhibition assays, which showed promising results in the high nanomolar range. These results provide structural considerations that may guide further hit-to-lead optimization toward improved anti-HIV drugs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computer-aided Instructional System for Transmission Line Simulation.

ERIC Educational Resources Information Center

Reinhard, Erwin A.; Roth, Charles H., Jr.

A computer-aided instructional system has been developed which utilizes dynamic computer-controlled graphic displays and which requires student interaction with a computer simulation in an instructional mode. A numerical scheme has been developed for digital simulation of a uniform, distortionless transmission line with resistive terminations and…

Proceedings of the Workshop on Computational Aspects in the Control of Flexible Systems, part 1

NASA Technical Reports Server (NTRS)

Taylor, Lawrence W., Jr. (Compiler)

1989-01-01

Control/Structures Integration program software needs, computer aided control engineering for flexible spacecraft, computer aided design, computational efficiency and capability, modeling and parameter estimation, and control synthesis and optimization software for flexible structures and robots are among the topics discussed.

Computer aided field editing in the DHS context: the Turkey experiment.

PubMed

Cushing, J; Loaiza, E

1994-01-01

"In this study two types of field editing used during the Turkey Demographic and Health Survey are compared. These two types of editing are computer aided field editing and manual editing. It is known that manual editing by field editors is a tedious job in which errors especially on skip questions can be missed; however, with the aid of computers field editors could quickly find all occasions on which an interviewer incorrectly followed a skip instruction. At the end of the experiment it has been found...that the field editing done with the aid of a notebook computer was consistently better than that done in the standard manual manner." (SUMMARY IN TUR) excerpt

Contributions of computational chemistry and biophysical techniques to fragment-based drug discovery.

PubMed

Gozalbes, Rafael; Carbajo, Rodrigo J; Pineda-Lucena, Antonio

2010-01-01

In the last decade, fragment-based drug discovery (FBDD) has evolved from a novel approach in the search of new hits to a valuable alternative to the high-throughput screening (HTS) campaigns of many pharmaceutical companies. The increasing relevance of FBDD in the drug discovery universe has been concomitant with an implementation of the biophysical techniques used for the detection of weak inhibitors, e.g. NMR, X-ray crystallography or surface plasmon resonance (SPR). At the same time, computational approaches have also been progressively incorporated into the FBDD process and nowadays several computational tools are available. These stretch from the filtering of huge chemical databases in order to build fragment-focused libraries comprising compounds with adequate physicochemical properties, to more evolved models based on different in silico methods such as docking, pharmacophore modelling, QSAR and virtual screening. In this paper we will review the parallel evolution and complementarities of biophysical techniques and computational methods, providing some representative examples of drug discovery success stories by using FBDD.

Quality indexing with computer-aided lexicography

NASA Technical Reports Server (NTRS)

Buchan, Ronald L.

1992-01-01

Indexing with computers is a far cry from indexing with the first indexing tool, the manual card sorter. With the aid of computer-aided lexicography, both indexing and indexing tools can provide standardization, consistency, and accuracy, resulting in greater quality control than ever before. A brief survey of computer activity in indexing is presented with detailed illustrations from NASA activity. Applications from techniques mentioned, such as Retrospective Indexing (RI), can be made to many indexing systems. In addition to improving the quality of indexing with computers, the improved efficiency with which certain tasks can be done is demonstrated.

Barratt on middeck

NASA Image and Video Library

2011-02-25

S133-E-006036 (25 Feb. 2011) --- Astronaut Michael Barratt, STS-133 mission specialist, works with the Microbe Group Activation Pack containing eight Fluid Processing Apparatuses on the middeck of space shuttle Discovery while en route to a rendezvous with the International Space Station. A previous set of similar tests made a key discovery about the mechanism that makes salmonella more infectious, aiding the fight against food poisoning on Earth. Photo credit: NASA or National Aeronautics and Space Administration

COMPUTER-AIDED DATA ACQUISITION FOR COMBUSTION EXPERIMENTS

EPA Science Inventory

The article describes the use of computer-aided data acquisition techniques to aid the research program of the Combustion Research Branch (CRB) of the U.S. EPA's Air and Energy Engineering Research Laboratory (AEERL) in Research Triangle Park, NC, in particular on CRB's bench-sca...

Computer-aided decision support systems for endoscopy in the gastrointestinal tract: a review.

PubMed

Liedlgruber, Michael; Uhl, Andreas

2011-01-01

Today, medical endoscopy is a widely used procedure to inspect the inner cavities of the human body. The advent of endoscopic imaging techniques-allowing the acquisition of images or videos-created the possibility for the development of the whole new branch of computer-aided decision support systems. Such systems aim at helping physicians to identify possibly malignant abnormalities more accurately. At the beginning of this paper, we give a brief introduction to the history of endoscopy, followed by introducing the main types of endoscopes which emerged so far (flexible endoscope, wireless capsule endoscope, and confocal laser endomicroscope). We then give a brief introduction to computer-aided decision support systems specifically targeted at endoscopy in the gastrointestinal tract. Then we present general facts and figures concerning computer-aided decision support systems and summarize work specifically targeted at computer-aided decision support in the gastrointestinal tract. This summary is followed by a discussion of some common issues concerning the approaches reviewed and suggestions of possible ways to resolve them.

Manipulating the Geometric Computer-aided Design of the Operational Requirements-based Casualty Assessment Model within BRL-CAD

DTIC Science & Technology

2018-03-30

ARL-TR-8336 ● MAR 2018 US Army Research Laboratory Manipulating the Geometric Computer-aided Design of the Operational...so designated by other authorized documents. Citation of manufacturer’s or trade names does not constitute an official endorsement or approval of...Army Research Laboratory Manipulating the Geometric Computer-aided Design of the Operational Requirements-based Casualty Assessment Model within

Increasing productivity of the McAuto CAD/CAE system by user-specific applications programming

NASA Technical Reports Server (NTRS)

Plotrowski, S. M.; Vu, T. H.

1985-01-01

Significant improvements in the productivity of the McAuto Computer-Aided Design/Computer-Aided Engineering (CAD/CAE) system were achieved by applications programming using the system's own Graphics Interactive Programming language (GRIP) and the interface capabilities with the main computer on which the system resides. The GRIP programs for creating springs, bar charts, finite element model representations and aiding management planning are presented as examples.

Possible Computer Vision Systems and Automated or Computer-Aided Edging and Trimming

Treesearch

Philip A. Araman

1990-01-01

This paper discusses research which is underway to help our industry reduce costs, increase product volume and value recovery, and market more accurately graded and described products. The research is part of a team effort to help the hardwood sawmill industry automate with computer vision systems, and computer-aided or computer controlled processing. This paper...

Features of Computer-Based Decision Aids: Systematic Review, Thematic Synthesis, and Meta-Analyses.

PubMed

Syrowatka, Ania; Krömker, Dörthe; Meguerditchian, Ari N; Tamblyn, Robyn

2016-01-26

Patient information and education, such as decision aids, are gradually moving toward online, computer-based environments. Considerable research has been conducted to guide content and presentation of decision aids. However, given the relatively new shift to computer-based support, little attention has been given to how multimedia and interactivity can improve upon paper-based decision aids. The first objective of this review was to summarize published literature into a proposed classification of features that have been integrated into computer-based decision aids. Building on this classification, the second objective was to assess whether integration of specific features was associated with higher-quality decision making. Relevant studies were located by searching MEDLINE, Embase, CINAHL, and CENTRAL databases. The review identified studies that evaluated computer-based decision aids for adults faced with preference-sensitive medical decisions and reported quality of decision-making outcomes. A thematic synthesis was conducted to develop the classification of features. Subsequently, meta-analyses were conducted based on standardized mean differences (SMD) from randomized controlled trials (RCTs) that reported knowledge or decisional conflict. Further subgroup analyses compared pooled SMDs for decision aids that incorporated a specific feature to other computer-based decision aids that did not incorporate the feature, to assess whether specific features improved quality of decision making. Of 3541 unique publications, 58 studies met the target criteria and were included in the thematic synthesis. The synthesis identified six features: content control, tailoring, patient narratives, explicit values clarification, feedback, and social support. A subset of 26 RCTs from the thematic synthesis was used to conduct the meta-analyses. As expected, computer-based decision aids performed better than usual care or alternative aids; however, some features performed better than others. Integration of content control improved quality of decision making (SMD 0.59 vs 0.23 for knowledge; SMD 0.39 vs 0.29 for decisional conflict). In contrast, tailoring reduced quality of decision making (SMD 0.40 vs 0.71 for knowledge; SMD 0.25 vs 0.52 for decisional conflict). Similarly, patient narratives also reduced quality of decision making (SMD 0.43 vs 0.65 for knowledge; SMD 0.17 vs 0.46 for decisional conflict). Results were varied for different types of explicit values clarification, feedback, and social support. Integration of media rich or interactive features into computer-based decision aids can improve quality of preference-sensitive decision making. However, this is an emerging field with limited evidence to guide use. The systematic review and thematic synthesis identified features that have been integrated into available computer-based decision aids, in an effort to facilitate reporting of these features and to promote integration of such features into decision aids. The meta-analyses and associated subgroup analyses provide preliminary evidence to support integration of specific features into future decision aids. Further research can focus on clarifying independent contributions of specific features through experimental designs and refining the designs of features to improve effectiveness.

Computer Skill Acquisition and Retention: The Effects of Computer-Aided Self-Explanation

ERIC Educational Resources Information Center

Chi, Tai-Yin

2016-01-01

This research presents an experimental study to determine to what extent computer skill learners can benefit from generating self-explanation with the aid of different computer-based visualization technologies. Self-explanation was stimulated with dynamic visualization (Screencast), static visualization (Screenshot), or verbal instructions only,…

What's your relationship with computerized manufacturing technologies -- functional, dysfunctional or non-existent?

Treesearch

Jan Wiedenbeck; Jeff Parsons; Bruce Beeken

2009-01-01

Computer-aided manufacturing (CAM), in which computer-aided design (CAD) and computer numerically controlled (CNC) machining are integrated for the production of parts, became a viable option for the woodworking industry in the 1980s.

WINCADRE (COMPUTER-AIDED DATA REVIEW AND EVALUATION)

EPA Science Inventory

WinCADRE (Computer-Aided Data Review and Evaluation) is a Windows -based program designed for computer-assisted data validation. WinCADRE is a powerful tool which significantly decreases data validation turnaround time. The electronic-data-deliverable format has been designed ...

A View of the Science Education Research Literature: Scientific Discovery Learning with Computer Simulations.

ERIC Educational Resources Information Center

Robinson, William R.

2000-01-01

Describes a review of research that addresses the effectiveness of simulations in promoting scientific discovery learning and the problems that learners may encounter when using discovery learning. (WRM)

Structural Genomics and Drug Discovery for Infectious Diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, W.F.

The application of structural genomics methods and approaches to proteins from organisms causing infectious diseases is making available the three dimensional structures of many proteins that are potential drug targets and laying the groundwork for structure aided drug discovery efforts. There are a number of structural genomics projects with a focus on pathogens that have been initiated worldwide. The Center for Structural Genomics of Infectious Diseases (CSGID) was recently established to apply state-of-the-art high throughput structural biology technologies to the characterization of proteins from the National Institute for Allergy and Infectious Diseases (NIAID) category A-C pathogens and organisms causing emerging,more » or re-emerging infectious diseases. The target selection process emphasizes potential biomedical benefits. Selected proteins include known drug targets and their homologs, essential enzymes, virulence factors and vaccine candidates. The Center also provides a structure determination service for the infectious disease scientific community. The ultimate goal is to generate a library of structures that are available to the scientific community and can serve as a starting point for further research and structure aided drug discovery for infectious diseases. To achieve this goal, the CSGID will determine protein crystal structures of 400 proteins and protein-ligand complexes using proven, rapid, highly integrated, and cost-effective methods for such determination, primarily by X-ray crystallography. High throughput crystallographic structure determination is greatly aided by frequent, convenient access to high-performance beamlines at third-generation synchrotron X-ray sources.« less

Biomedical and development paradigms in AIDS prevention.

PubMed Central

Wolffers, I.

2000-01-01

In the fight against the HIV/AIDS pandemic different approaches can be distinguished, reflecting professional backgrounds, world views and political interests. One important distinction is between the biomedical and the development paradigms. The biomedical paradigm is characterized by individualization and the concept of "risk". This again is related to the concept of the market where health is a product of services and progress a series of new discoveries that can be marketed. The development paradigm is characterized by participation of the different stakeholders and by community work. The concept "vulnerability" is important in the development paradigm and emphasis is placed on efforts to decrease this vulnerability in a variety of sustainable ways. Biomedical technology is definitely one of the tools in these efforts. In the beginning of the pandemic the biomedical approach was important for the discovery of the virus and understanding its epidemiology. Later, stakeholders became involved. In the light of absence of treatment or vaccines, the development paradigm became more important and the two approaches were more in balance. However, since the reports about effective treatment of AIDS and hope of development of vaccines, the biomedical paradigm has become a leading principle in many HIV/AIDS prevention programmes. There is a need for a better balance between the two paradigms. Especially in developing countries, where it is not realistic to think that sustainable biomedical interventions can be organized on a short-term basis, it would be counterproductive to base our efforts to deal with HIV/AIDS exclusively on the biomedical approach. PMID:10743300

Helical gears with circular arc teeth: Generation, geometry, precision and adjustment to errors, computer aided simulation of conditions of meshing and bearing contact

NASA Technical Reports Server (NTRS)

Litvin, Faydor L.; Tsay, Chung-Biau

1987-01-01

The authors have proposed a method for the generation of circular arc helical gears which is based on the application of standard equipment, worked out all aspects of the geometry of the gears, proposed methods for the computer aided simulation of conditions of meshing and bearing contact, investigated the influence of manufacturing and assembly errors, and proposed methods for the adjustment of gears to these errors. The results of computer aided solutions are illustrated with computer graphics.

Reinforced Adversarial Neural Computer for de Novo Molecular Design.

PubMed

Putin, Evgeny; Asadulaev, Arip; Ivanenkov, Yan; Aladinskiy, Vladimir; Sanchez-Lengeling, Benjamin; Aspuru-Guzik, Alán; Zhavoronkov, Alex

2018-06-12

In silico modeling is a crucial milestone in modern drug design and development. Although computer-aided approaches in this field are well-studied, the application of deep learning methods in this research area is at the beginning. In this work, we present an original deep neural network (DNN) architecture named RANC (Reinforced Adversarial Neural Computer) for the de novo design of novel small-molecule organic structures based on the generative adversarial network (GAN) paradigm and reinforcement learning (RL). As a generator RANC uses a differentiable neural computer (DNC), a category of neural networks, with increased generation capabilities due to the addition of an explicit memory bank, which can mitigate common problems found in adversarial settings. The comparative results have shown that RANC trained on the SMILES string representation of the molecules outperforms its first DNN-based counterpart ORGANIC by several metrics relevant to drug discovery: the number of unique structures, passing medicinal chemistry filters (MCFs), Muegge criteria, and high QED scores. RANC is able to generate structures that match the distributions of the key chemical features/descriptors (e.g., MW, logP, TPSA) and lengths of the SMILES strings in the training data set. Therefore, RANC can be reasonably regarded as a promising starting point to develop novel molecules with activity against different biological targets or pathways. In addition, this approach allows scientists to save time and covers a broad chemical space populated with novel and diverse compounds.

Physics-based scoring of protein-ligand interactions: explicit polarizability, quantum mechanics and free energies.

PubMed

Bryce, Richard A

2011-04-01

The ability to accurately predict the interaction of a ligand with its receptor is a key limitation in computer-aided drug design approaches such as virtual screening and de novo design. In this article, we examine current strategies for a physics-based approach to scoring of protein-ligand affinity, as well as outlining recent developments in force fields and quantum chemical techniques. We also consider advances in the development and application of simulation-based free energy methods to study protein-ligand interactions. Fuelled by recent advances in computational algorithms and hardware, there is the opportunity for increased integration of physics-based scoring approaches at earlier stages in computationally guided drug discovery. Specifically, we envisage increased use of implicit solvent models and simulation-based scoring methods as tools for computing the affinities of large virtual ligand libraries. Approaches based on end point simulations and reference potentials allow the application of more advanced potential energy functions to prediction of protein-ligand binding affinities. Comprehensive evaluation of polarizable force fields and quantum mechanical (QM)/molecular mechanical and QM methods in scoring of protein-ligand interactions is required, particularly in their ability to address challenging targets such as metalloproteins and other proteins that make highly polar interactions. Finally, we anticipate increasingly quantitative free energy perturbation and thermodynamic integration methods that are practical for optimization of hits obtained from screened ligand libraries.

Computer-Aided Engineering Education at the K.U. Leuven.

ERIC Educational Resources Information Center

Snoeys, R.; Gobin, R.

1987-01-01

Describes some recent initiatives and developments in the computer-aided design program in the engineering faculty of the Katholieke Universiteit Leuven (Belgium). Provides a survey of the engineering curriculum, the computer facilities, and the main software packages available. (TW)

Software Tools for Shipbuilding Productivity

DTIC Science & Technology

1984-12-01

shipbuilding, is that design, manufacturing and robotic technology applications to shipbuilding have been proven. all aspects of shipbuilding is now a task...technical information about the process of Computer Aided Design (CAD) and Computer Aided Manufacturing (CAM) effectively has been a problem of serious and...Design (CAD) 3.4.1 CAD System Components 3.4.2 CAD System Benefits 3.4.3 New and Future CAD Technologies Computer Aided Manufacturing (CAM) 3.5.1 CAM

Digital data acquisition for a CAD/CAM-fabricated titanium framework and zirconium oxide restorations for an implant-supported fixed complete dental prosthesis.

PubMed

Lin, Wei-Shao; Metz, Michael J; Pollini, Adrien; Ntounis, Athanasios; Morton, Dean

2014-12-01

This dental technique report describes a digital workflow with digital data acquisition at the implant level, computer-aided design and computer-aided manufacturing fabricated, tissue-colored, anodized titanium framework, individually luted zirconium oxide restorations, and autopolymerizing injection-molded acrylic resin to fabricate an implant-supported, metal-ceramic-resin fixed complete dental prosthesis in an edentulous mandible. The 1-step computer-aided design and computer-aided manufacturing fabrication of titanium framework and zirconium oxide restorations can provide a cost-effective alternative to the conventional metal-resin fixed complete dental prosthesis. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Correction of facial and mandibular asymmetry using a computer aided design/computer aided manufacturing prefabricated titanium implant.

PubMed

Watson, Jason; Hatamleh, Muhanad; Alwahadni, Ahed; Srinivasan, Dilip

2014-05-01

Patients with significant craniofacial asymmetry may have functional problems associated with their occlusion and aesthetic concerns related to the imbalance in soft and hard tissue profiles. This report details a case of facial asymmetry secondary to left mandible angle deficiency due to undergoing previous radiotherapy. We describe the correction of the bony deformity using computer aided design/computer aided manufacturing custom-made titanium onlay using novel direct metal laser sintering. The direct metal laser sintering onlay proved a very accurate operative fit and showed a good aesthetic correction of the bony defect with no reported complications postoperatively. It is a useful low-morbidity technique, and there is no resorption or associated donor-site complications.

Classification of Computer-Aided Design-Computer-Aided Manufacturing Applications for the Reconstruction of Cranio-Maxillo-Facial Defects.

PubMed

Wauters, Lauri D J; Miguel-Moragas, Joan San; Mommaerts, Maurice Y

2015-11-01

To gain insight into the methodology of different computer-aided design-computer-aided manufacturing (CAD-CAM) applications for the reconstruction of cranio-maxillo-facial (CMF) defects. We reviewed and analyzed the available literature pertaining to CAD-CAM for use in CMF reconstruction. We proposed a classification system of the techniques of implant and cutting, drilling, and/or guiding template design and manufacturing. The system consisted of 4 classes (I-IV). These classes combine techniques used for both the implant and template to most accurately describe the methodology used. Our classification system can be widely applied. It should facilitate communication and immediate understanding of the methodology of CAD-CAM applications for the reconstruction of CMF defects.

Dual-scan technique for the customization of zirconia computer-aided design/computer-aided manufacturing frameworks.

PubMed

Andreiuolo, Rafael Ferrone; Sabrosa, Carlos Eduardo; Dias, Katia Regina H Cervantes

2013-09-01

The use of bi-layered all-ceramic crowns has continuously grown since the introduction of computer-aided design/computer-aided manufacturing (CAD/CAM) zirconia cores. Unfortunately, despite the outstanding mechanical properties of zirconia, problems related to porcelain cracking or chipping remain. One of the reasons for this is that ceramic copings are usually milled to uniform thicknesses of 0.3-0.6 mm around the whole tooth preparation. This may not provide uniform thickness or appropriate support for the veneering porcelain. To prevent these problems, the dual-scan technique demonstrates an alternative that allows the restorative team to customize zirconia CAD/CAM frameworks with adequate porcelain thickness and support in a simple manner.

KSC00pp1672

NASA Image and Video Library

2000-10-24

Viewed from the side, orbiter Discovery, with its seven-member crew, touches down on the landing strip at Edwards Air Force Base, Calif., after an 11-day mission to the International Space Station. The orbiter’s main landing gear touched down on EAFB runway 22 at 5 p.m. With the aid of its drag chute, Discovery came to a complete stop at 5:01 p.m. At the conclusion of mission STS-92, Discovery and crew had traveled about 5.3 million statute miles. Following vehicle safing and preliminary offloading efforts, workers will begin preparations for Discovery’s transcontinental ferry flight back to KSC on the back of NASA’s modified Boeing 747

KSC-00pp1671

NASA Image and Video Library

2000-10-24

Orbiter Discovery, with its seven-member crew, approaches the landing strip at Edwards Air Force Base, Calif., after an 11-day mission to the International Space Station. The orbiter’s main landing gear touched down on EAFB runway 22 at 5 p.m. With the aid of its drag chute, Discovery came to a complete stop at 5:01 p.m. At the conclusion of mission STS-92, Discovery and crew had traveled about 5.3 million statute miles. Following vehicle safing and preliminary offloading efforts, workers will begin preparations for Discovery’s transcontinental ferry flight back to KSC on the back of NASA’s modified Boeing 747

KSC00pp1671

NASA Image and Video Library

2000-10-24

Orbiter Discovery, with its seven-member crew, approaches the landing strip at Edwards Air Force Base, Calif., after an 11-day mission to the International Space Station. The orbiter’s main landing gear touched down on EAFB runway 22 at 5 p.m. With the aid of its drag chute, Discovery came to a complete stop at 5:01 p.m. At the conclusion of mission STS-92, Discovery and crew had traveled about 5.3 million statute miles. Following vehicle safing and preliminary offloading efforts, workers will begin preparations for Discovery’s transcontinental ferry flight back to KSC on the back of NASA’s modified Boeing 747

KSC00pp1669

NASA Image and Video Library

2000-10-24

With its drag chute deployed, orbiter Discovery and its seven-member crew roll toward a stop at Edwards Air Force Base, Calif., after an 11-day mission to the International Space Station. The orbiter’s main landing gear touched down on EAFB runway 22 at 5 p.m. With the aid of its drag chute, Discovery came to a complete stop at 5:01 p.m. At the conclusion of mission STS-92, Discovery and crew had traveled about 5.3 million statute miles. Following vehicle safing and preliminary offloading efforts, workers will begin preparations for Discovery’s transcontinental ferry flight back to KSC on the back of NASA’s modified Boeing 747

KSC-00pp1669

NASA Image and Video Library

2000-10-24

With its drag chute deployed, orbiter Discovery and its seven-member crew roll toward a stop at Edwards Air Force Base, Calif., after an 11-day mission to the International Space Station. The orbiter’s main landing gear touched down on EAFB runway 22 at 5 p.m. With the aid of its drag chute, Discovery came to a complete stop at 5:01 p.m. At the conclusion of mission STS-92, Discovery and crew had traveled about 5.3 million statute miles. Following vehicle safing and preliminary offloading efforts, workers will begin preparations for Discovery’s transcontinental ferry flight back to KSC on the back of NASA’s modified Boeing 747

KSC00pp1670

NASA Image and Video Library

2000-10-24

Orbiter Discovery, with its seven-member crew, touches down on the landing strip at Edwards Air Force Base, Calif., after an 11-day mission to the International Space Station. The orbiter’s main landing gear touched down on EAFB runway 22 at 5 p.m. With the aid of its drag chute, Discovery came to a complete stop at 5:01 p.m. At the conclusion of mission STS-92, Discovery and crew had traveled about 5.3 million statute miles. Following vehicle safing and preliminary offloading efforts, workers will begin preparations for Discovery’s transcontinental ferry flight back to KSC on the back of NASA’s modified Boeing 747

Computer Simulated Visual and Tactile Feedback as an Aid to Manipulator and Vehicle Control,

DTIC Science & Technology

1981-05-08

STATEMENT ........................ 8 Artificial Intellegence Versus Supervisory Control ....... 8 Computer Generation of Operator Feedback...operator. Artificial Intelligence Versus Supervisory Control The use of computers to aid human operators can be divided into two catagories: artificial ...operator. Artificial intelligence ( A. I. ) attempts to give the computer maximum intelligence and to replace all operator functions by the computer

Virtual Reality versus Computer-Aided Exposure Treatments for Fear of Flying

ERIC Educational Resources Information Center

Tortella-Feliu, Miquel; Botella, Cristina; Llabres, Jordi; Breton-Lopez, Juana Maria; del Amo, Antonio Riera; Banos, Rosa M.; Gelabert, Joan M.

2011-01-01

Evidence is growing that two modalities of computer-based exposure therapies--virtual reality and computer-aided psychotherapy--are effective in treating anxiety disorders, including fear of flying. However, they have not yet been directly compared. The aim of this study was to analyze the efficacy of three computer-based exposure treatments for…

The Implications of Cognitive Psychology for Computer-Based Learning Tools.

ERIC Educational Resources Information Center

Kozma, Robert B.

1987-01-01

Defines cognitive computer tools as software programs that use the control capabilities of computers to amplify, extend, or enhance human cognition; suggests seven ways in which computers can aid learning; and describes the "Learning Tool," a software package for the Apple Macintosh microcomputer that is designed to aid learning of…

Artificial Intelligence and Computer Assisted Instruction. CITE Report No. 4.

ERIC Educational Resources Information Center

Elsom-Cook, Mark

The purpose of the paper is to outline some of the major ways in which artificial intelligence research and techniques can affect usage of computers in an educational environment. The role of artificial intelligence is defined, and the difference between Computer Aided Instruction (CAI) and Intelligent Computer Aided Instruction (ICAI) is…

Electronic Circuit Analysis Language (ECAL)

NASA Astrophysics Data System (ADS)

Chenghang, C.

1983-03-01

The computer aided design technique is an important development in computer applications and it is an important component of computer science. The special language for electronic circuit analysis is the foundation of computer aided design or computer aided circuit analysis (abbreviated as CACD and CACA) of simulated circuits. Electronic circuit analysis language (ECAL) is a comparatively simple and easy to use circuit analysis special language which uses the FORTRAN language to carry out the explanatory executions. It is capable of conducting dc analysis, ac analysis, and transient analysis of a circuit. Futhermore, the results of the dc analysis can be used directly as the initial conditions for the ac and transient analyses.

Translational systems biology using an agent-based approach for dynamic knowledge representation: An evolutionary paradigm for biomedical research.

PubMed

An, Gary C

2010-01-01

The greatest challenge facing the biomedical research community is the effective translation of basic mechanistic knowledge into clinically effective therapeutics. This challenge is most evident in attempts to understand and modulate "systems" processes/disorders, such as sepsis, cancer, and wound healing. Formulating an investigatory strategy for these issues requires the recognition that these are dynamic processes. Representation of the dynamic behavior of biological systems can aid in the investigation of complex pathophysiological processes by augmenting existing discovery procedures by integrating disparate information sources and knowledge. This approach is termed Translational Systems Biology. Focusing on the development of computational models capturing the behavior of mechanistic hypotheses provides a tool that bridges gaps in the understanding of a disease process by visualizing "thought experiments" to fill those gaps. Agent-based modeling is a computational method particularly well suited to the translation of mechanistic knowledge into a computational framework. Utilizing agent-based models as a means of dynamic hypothesis representation will be a vital means of describing, communicating, and integrating community-wide knowledge. The transparent representation of hypotheses in this dynamic fashion can form the basis of "knowledge ecologies," where selection between competing hypotheses will apply an evolutionary paradigm to the development of community knowledge.

Virtual screening for development of new effective compounds against Staphylococcus aureus.

PubMed

Diniz, Roseane Costa; Soares, Lucas Weba; da Silva, Luis Claudio Nascimento

2018-03-26

Staphylococcus aureus is a notorious pathogenic bacterium causing a wide range of diseases from soft-tissue contamination, to more serious and deep-seated infections. This species is highlighted by its ability to express several kinds of virulence factors and to acquire genes related to drug resistance. Target this number of factors to design any drug is not an easy task. In this review we discuss the importance of computational methods to impulse the development of new drugs against S. aureus. The application of docking methods to screen large library of natural or synthetic compounds and to provide insights into action mechanisms is demonstrated. Particularly, highlighted the studies that validated in silico results with biochemical and microbiological assays. We also comment the computer-aided design of new molecules using some known inhibitors. The confirmation of in silico results with biochemical and microbiological assays allowed the identification of lead molecules that could be used for drug design such as rhodomyrtone, quinuclidine, berberine (and their derivative compounds). The fast development in the computational methods is essential to improve our ability to discovery new drugs, as well as to expand understanding about drug-target interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

PubMed Central

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

WINCADRE INORGANIC (WINDOWS COMPUTER-AIDED DATA REVIEW AND EVALUATION)

EPA Science Inventory

WinCADRE (Computer-Aided Data Review and Evaluation) is a Windows -based program designed for computer-assisted data validation. WinCADRE is a powerful tool which significantly decreases data validation turnaround time. The electronic-data-deliverable format has been designed in...

The path to producing pharmaceuticals from natural products uncovered by academia-from the perspective of a science coordinator.

PubMed

Fujie, Akihiko

2017-01-01

To actualize the invention of all-Japanese medicines, the Department of Innovative Drug Discovery and Development (iD3) in the Japan Agency for Medical Research and Development (AMED) serves as the headquarters for the Drug Discovery Support Network. iD3 assists with creating research strategies for the seeds of medicines discovered by academia and provides technological support, intellectual property management, and aid for applying the seeds through industry-led efforts. In this review, from the perspective of a science coordinator, I will describe the current activities of the drug discovery support network and iD3 as well as the challenges and future developments of pharmaceutical research and development using the natural product drug discovery method.

Collaborative drug discovery for More Medicines for Tuberculosis (MM4TB)

PubMed Central

Ekins, Sean; Spektor, Anna Coulon; Clark, Alex M.; Dole, Krishna; Bunin, Barry A.

2016-01-01

Neglected disease drug discovery is generally poorly funded compared with major diseases and hence there is an increasing focus on collaboration and precompetitive efforts such as public–private partnerships (PPPs). The More Medicines for Tuberculosis (MM4TB) project is one such collaboration funded by the EU with the goal of discovering new drugs for tuberculosis. Collaborative Drug Discovery has provided a commercial web-based platform called CDD Vault which is a hosted collaborative solution for securely sharing diverse chemistry and biology data. Using CDD Vault alongside other commercial and free cheminformatics tools has enabled support of this and other large collaborative projects, aiding drug discovery efforts and fostering collaboration. We will describe CDD's efforts in assisting with the MM4TB project. PMID:27884746

In silico fragment-based drug design.

PubMed

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.

Discovery and study of novel protein tyrosine phosphatase 1B inhibitors

NASA Astrophysics Data System (ADS)

Zhang, Qian; Chen, Xi; Feng, Changgen

2017-10-01

Protein tyrosine phosphatase 1B (PTP1B) is considered to be a target for therapy of type II diabetes and obesity. So it is of great significance to take advantage of a computer aided drug design protocol involving the structured-based virtual screening with docking simulations for fast searching small molecule PTP1B inhibitors. Based on optimized complex structure of PTP1B bound with specific inhibitor of IX1, structured-based virtual screening against a library of natural products containing 35308 molecules, which was constructed based on Traditional Chinese Medicine database@ Taiwan (TCM database@ Taiwan), was conducted to determine the occurrence of PTP1B inhibitors using the Lubbock module and CDOCKER module from Discovery Studio 3.1 software package. The results were further filtered by predictive ADME simulation and predictive toxic simulation. As a result, 2 good drug-like molecules, namely para-benzoquinone compound 1 and Clavepictine analogue 2 were identified ultimately with the dock score of original inhibitor (IX1) and the receptor as a threshold. Binding model analyses revealed that these two candidate compounds have good interactions with PTP1B. The PTP1B inhibitory activity of compound 2 hasn't been reported before. The optimized compound 2 has higher scores and deserves further study.

MPD3: a useful medicinal plants database for drug designing.

PubMed

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 .

Start-ups Bring AI to Pathology.

PubMed

2018-04-01

New startups are developing pattern-recognition algorithms that could one day help pathologists more accurately spot tumors on digitized tissue images, thereby aiding in diagnosis, treatment, drug discovery, and more. ©2018 American Association for Cancer Research.

Computer-aided US diagnosis of breast lesions by using cell-based contour grouping.

PubMed

Cheng, Jie-Zhi; Chou, Yi-Hong; Huang, Chiun-Sheng; Chang, Yeun-Chung; Tiu, Chui-Mei; Chen, Kuei-Wu; Chen, Chung-Ming

2010-06-01

To develop a computer-aided diagnostic algorithm with automatic boundary delineation for differential diagnosis of benign and malignant breast lesions at ultrasonography (US) and investigate the effect of boundary quality on the performance of a computer-aided diagnostic algorithm. This was an institutional review board-approved retrospective study with waiver of informed consent. A cell-based contour grouping (CBCG) segmentation algorithm was used to delineate the lesion boundaries automatically. Seven morphologic features were extracted. The classifier was a logistic regression function. Five hundred twenty breast US scans were obtained from 520 subjects (age range, 15-89 years), including 275 benign (mean size, 15 mm; range, 5-35 mm) and 245 malignant (mean size, 18 mm; range, 8-29 mm) lesions. The newly developed computer-aided diagnostic algorithm was evaluated on the basis of boundary quality and differentiation performance. The segmentation algorithms and features in two conventional computer-aided diagnostic algorithms were used for comparative study. The CBCG-generated boundaries were shown to be comparable with the manually delineated boundaries. The area under the receiver operating characteristic curve (AUC) and differentiation accuracy were 0.968 +/- 0.010 and 93.1% +/- 0.7, respectively, for all 520 breast lesions. At the 5% significance level, the newly developed algorithm was shown to be superior to the use of the boundaries and features of the two conventional computer-aided diagnostic algorithms in terms of AUC (0.974 +/- 0.007 versus 0.890 +/- 0.008 and 0.788 +/- 0.024, respectively). The newly developed computer-aided diagnostic algorithm that used a CBCG segmentation method to measure boundaries achieved a high differentiation performance. Copyright RSNA, 2010

Estimation of the failure risk of a maxillary premolar with different crack depths with endodontic treatment by computer-aided design/computer-aided manufacturing ceramic restorations.

PubMed

Lin, Chun-Li; Chang, Yen-Hsiang; Hsieh, Shih-Kai; Chang, Wen-Jen

2013-03-01

This study evaluated the risk of failure for an endodontically treated premolar with different crack depths, which was shearing toward the pulp chamber and was restored by using 3 different computer-aided design/computer-aided manufacturing ceramic restoration configurations. Three 3-dimensional finite element models designed with computer-aided design/computer-aided manufacturing ceramic onlay, endocrown, and conventional crown restorations were constructed to perform simulations. The Weibull function was incorporated with finite element analysis to calculate the long-term failure probability relative to different load conditions. The results indicated that the stress values on the enamel, dentin, and luting cement for endocrown restorations exhibited the lowest values relative to the other 2 restoration methods. Weibull analysis revealed that the overall failure probabilities in a shallow cracked premolar were 27%, 2%, and 1% for the onlay, endocrown, and conventional crown restorations, respectively, in the normal occlusal condition. The corresponding values were 70%, 10%, and 2% for the depth cracked premolar. This numeric investigation suggests that the endocrown provides sufficient fracture resistance only in a shallow cracked premolar with endodontic treatment. The conventional crown treatment can immobilize the premolar for different cracked depths with lower failure risk. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Advances in computer-aided well-test interpretation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horne, R.N.

1994-07-01

Despite the feeling expressed several times over the past 40 years that well-test analysis had reached it peak development, an examination of recent advances shows continuous expansion in capability, with future improvement likely. The expansion in interpretation capability over the past decade arose mainly from the development of computer-aided techniques, which, although introduced 20 years ago, have come into use only recently. The broad application of computer-aided interpretation originated with the improvement of the methodologies and continued with the expansion in computer access and capability that accompanied the explosive development of the microcomputer industry. This paper focuses on the differentmore » pieces of the methodology that combine to constitute a computer-aided interpretation and attempts to compare some of the approaches currently used. Future directions of the approach are also discussed. The separate areas discussed are deconvolution, pressure derivatives, model recognition, nonlinear regression, and confidence intervals.« less

Features of Computer-Based Decision Aids: Systematic Review, Thematic Synthesis, and Meta-Analyses

PubMed Central

Krömker, Dörthe; Meguerditchian, Ari N; Tamblyn, Robyn

2016-01-01

Background Patient information and education, such as decision aids, are gradually moving toward online, computer-based environments. Considerable research has been conducted to guide content and presentation of decision aids. However, given the relatively new shift to computer-based support, little attention has been given to how multimedia and interactivity can improve upon paper-based decision aids. Objective The first objective of this review was to summarize published literature into a proposed classification of features that have been integrated into computer-based decision aids. Building on this classification, the second objective was to assess whether integration of specific features was associated with higher-quality decision making. Methods Relevant studies were located by searching MEDLINE, Embase, CINAHL, and CENTRAL databases. The review identified studies that evaluated computer-based decision aids for adults faced with preference-sensitive medical decisions and reported quality of decision-making outcomes. A thematic synthesis was conducted to develop the classification of features. Subsequently, meta-analyses were conducted based on standardized mean differences (SMD) from randomized controlled trials (RCTs) that reported knowledge or decisional conflict. Further subgroup analyses compared pooled SMDs for decision aids that incorporated a specific feature to other computer-based decision aids that did not incorporate the feature, to assess whether specific features improved quality of decision making. Results Of 3541 unique publications, 58 studies met the target criteria and were included in the thematic synthesis. The synthesis identified six features: content control, tailoring, patient narratives, explicit values clarification, feedback, and social support. A subset of 26 RCTs from the thematic synthesis was used to conduct the meta-analyses. As expected, computer-based decision aids performed better than usual care or alternative aids; however, some features performed better than others. Integration of content control improved quality of decision making (SMD 0.59 vs 0.23 for knowledge; SMD 0.39 vs 0.29 for decisional conflict). In contrast, tailoring reduced quality of decision making (SMD 0.40 vs 0.71 for knowledge; SMD 0.25 vs 0.52 for decisional conflict). Similarly, patient narratives also reduced quality of decision making (SMD 0.43 vs 0.65 for knowledge; SMD 0.17 vs 0.46 for decisional conflict). Results were varied for different types of explicit values clarification, feedback, and social support. Conclusions Integration of media rich or interactive features into computer-based decision aids can improve quality of preference-sensitive decision making. However, this is an emerging field with limited evidence to guide use. The systematic review and thematic synthesis identified features that have been integrated into available computer-based decision aids, in an effort to facilitate reporting of these features and to promote integration of such features into decision aids. The meta-analyses and associated subgroup analyses provide preliminary evidence to support integration of specific features into future decision aids. Further research can focus on clarifying independent contributions of specific features through experimental designs and refining the designs of features to improve effectiveness. PMID:26813512

Evolving Relevance of Neuroproteomics in Alzheimer's Disease.

PubMed

Lista, Simone; Zetterberg, Henrik; O'Bryant, Sid E; Blennow, Kaj; Hampel, Harald

2017-01-01

Substantial progress in the understanding of the biology of Alzheimer's disease (AD) has been achieved over the past decades. The early detection and diagnosis of AD and other age-related neurodegenerative diseases, however, remain a challenging scientific frontier. Therefore, the comprehensive discovery (relating to all individual, converging or diverging biochemical disease mechanisms), development, validation, and qualification of standardized biological markers with diagnostic and prognostic functions with a precise performance profile regarding specificity, sensitivity, and positive and negative predictive value are warranted.Methodological innovations in the area of exploratory high-throughput technologies, such as sequencing, microarrays, and mass spectrometry-based analyses of proteins/peptides, have led to the generation of large global molecular datasets from a multiplicity of biological systems, such as biological fluids, cells, tissues, and organs. Such methodological progress has shifted the attention to the execution of hypothesis-independent comprehensive exploratory analyses (opposed to the classical hypothesis-driven candidate approach), with the aim of fully understanding the biological systems in physiology and disease as a whole. The systems biology paradigm integrates experimental biology with accurate and rigorous computational modelling to describe and foresee the dynamic features of biological systems. The use of dynamically evolving technological platforms, including mass spectrometry, in the area of proteomics has enabled to rush the process of biomarker discovery and validation for refining significantly the diagnosis of AD. Currently, proteomics-which is part of the systems biology paradigm-is designated as one of the dominant matured sciences needed for the effective exploratory discovery of prospective biomarker candidates expected to play an effective role in aiding the early detection, diagnosis, prognosis, and therapy development in AD.

Low-Cost Computer-Aided Instruction/Computer-Managed Instruction (CAI/CMI) System: Feasibility Study. Final Report.

ERIC Educational Resources Information Center

Lintz, Larry M.; And Others

This study investigated the feasibility of a low cost computer-aided instruction/computer-managed instruction (CAI/CMI) system. Air Force instructors and training supervisors were surveyed to determine the potential payoffs of various CAI and CMI functions. Results indicated that a wide range of capabilities had potential for resident technical…

Computer Aided Drafting Packages for Secondary Education. Edition 1. Apple II and Macintosh. A MicroSIFT Quarterly Report.

ERIC Educational Resources Information Center

Pollard, Jim

This report reviews software packages for Apple Macintosh and Apple II computers available to secondary schools to teach computer-aided drafting (CAD). Products for the report were gathered through reviews of CAD periodicals, computers in education periodicals, advertisements, and teacher recommendations. The first section lists the primary…

Mechanistic insights into chemical and photochemical transformations of bismuth vanadate photoanodes

PubMed Central

Toma, Francesca M.; Cooper, Jason K.; Kunzelmann, Viktoria; McDowell, Matthew T.; Yu, Jie; Larson, David M.; Borys, Nicholas J.; Abelyan, Christine; Beeman, Jeffrey W.; Yu, Kin Man; Yang, Jinhui; Chen, Le; Shaner, Matthew R.; Spurgeon, Joshua; Houle, Frances A.; Persson, Kristin A.; Sharp, Ian D.

2016-01-01

Artificial photosynthesis relies on the availability of semiconductors that are chemically stable and can efficiently capture solar energy. Although metal oxide semiconductors have been investigated for their promise to resist oxidative attack, materials in this class can suffer from chemical and photochemical instability. Here we present a methodology for evaluating corrosion mechanisms and apply it to bismuth vanadate, a state-of-the-art photoanode. Analysis of changing morphology and composition under solar water splitting conditions reveals chemical instabilities that are not predicted from thermodynamic considerations of stable solid oxide phases, as represented by the Pourbaix diagram for the system. Computational modelling indicates that photoexcited charge carriers accumulated at the surface destabilize the lattice, and that self-passivation by formation of a chemically stable surface phase is kinetically hindered. Although chemical stability of metal oxides cannot be assumed, insight into corrosion mechanisms aids development of protection strategies and discovery of semiconductors with improved stability. PMID:27377305

Hypoxia inducible factor (HIF) as a model for studying inhibition of protein–protein interactions

PubMed Central

Burslem, George M.; Kyle, Hannah F.; Nelson, Adam; Edwards, Thomas A.

2017-01-01

The modulation of protein–protein interactions (PPIs) represents a major challenge in modern chemical biology. Current approaches (e.g. high-throughput screening, computer aided ligand design) are recognised as having limitations in terms of identification of hit matter. Considerable success has been achieved in terms of developing new approaches to PPI modulator discovery using the p53/hDM2 and Bcl-2 family of PPIs. However these important targets in oncology might be considered as “low-hanging-fruit”. Hypoxia inducible factor (HIF) is an emerging, but not yet fully validated target for cancer chemotherapy. Its role is to regulate the hypoxic response and it does so through a plethora of protein–protein interactions of varying topology, topography and complexity: its modulation represents an attractive approach to prevent development of new vasculature by hypoxic tumours. PMID:28878873

From tissue to silicon to plastic: three-dimensional printing in comparative anatomy and physiology

PubMed Central

Lauridsen, Henrik; Hansen, Kasper; Nørgård, Mathias Ørum; Wang, Tobias; Pedersen, Michael

2016-01-01

Comparative anatomy and physiology are disciplines related to structures and mechanisms in three-dimensional (3D) space. For the past centuries, scientific reports in these fields have relied on written descriptions and two-dimensional (2D) illustrations, but in recent years 3D virtual modelling has entered the scene. However, comprehending complex anatomical structures is hampered by reproduction on flat inherently 2D screens. One way to circumvent this problem is in the production of 3D-printed scale models. We have applied computed tomography and magnetic resonance imaging to produce digital models of animal anatomy well suited to be printed on low-cost 3D printers. In this communication, we report how to apply such technology in comparative anatomy and physiology to aid discovery, description, comprehension and communication, and we seek to inspire fellow researchers in these fields to embrace this emerging technology. PMID:27069653

Use of historic metabolic biotransformation data as a means of anticipating metabolic sites using MetaPrint2D and Bioclipse.

PubMed

Carlsson, Lars; Spjuth, Ola; Adams, Samuel; Glen, Robert C; Boyer, Scott

2010-07-01

Predicting metabolic sites is important in the drug discovery process to aid in rapid compound optimisation. No interactive tool exists and most of the useful tools are quite expensive. Here a fast and reliable method to analyse ligands and visualise potential metabolic sites is presented which is based on annotated metabolic data, described by circular fingerprints. The method is available via the graphical workbench Bioclipse, which is equipped with advanced features in cheminformatics. Due to the speed of predictions (less than 50 ms per molecule), scientists can get real time decision support when editing chemical structures. Bioclipse is a rich client, which means that all calculations are performed on the local computer and do not require network connection. Bioclipse and MetaPrint2D are free for all users, released under open source licenses, and available from http://www.bioclipse.net.

Component architecture in drug discovery informatics.

PubMed

Smith, Peter M

2002-05-01

This paper reviews the characteristics of a new model of computing that has been spurred on by the Internet, known as Netcentric computing. Developments in this model led to distributed component architectures, which, although not new ideas, are now realizable with modern tools such as Enterprise Java. The application of this approach to scientific computing, particularly in pharmaceutical discovery research, is discussed and highlighted by a particular case involving the management of biological assay data.

Computer Aided Drug Design: Success and Limitations.

PubMed

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.

Removal of Supernumerary Teeth Utilizing a Computer-Aided Design/Computer-Aided Manufacturing Surgical Guide.

PubMed

Jo, Chanwoo; Bae, Doohwan; Choi, Byungho; Kim, Jihun

2017-05-01

Supernumerary teeth need to be removed because they can cause various complications. Caution is needed because their removal can cause damage to permanent teeth or tooth germs in the local vicinity. Surgical guides have recently been used in maxillofacial surgery. Because surgical guides are designed through preoperative analysis by computer-aided design software and fabricated using a 3-dimensional printer applying computer-aided manufacturing technology, they increase the accuracy and predictability of surgery. This report describes 2 cases of removal of a mesiodens-1 from a child and 1 from an adolescent-using a surgical guide; these would have been difficult to remove with conventional surgical methods. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Web-Based Learning in the Computer-Aided Design Curriculum.

ERIC Educational Resources Information Center

Sung, Wen-Tsai; Ou, S. C.

2002-01-01

Applies principles of constructivism and virtual reality (VR) to computer-aided design (CAD) curriculum, particularly engineering, by integrating network, VR and CAD technologies into a Web-based learning environment that expands traditional two-dimensional computer graphics into a three-dimensional real-time simulation that enhances user…

Integrated Computer-Aided Drafting Instruction (ICADI).

ERIC Educational Resources Information Center

Chen, C. Y.; McCampbell, David H.

Until recently, computer-aided drafting and design (CAD) systems were almost exclusively operated on mainframes or minicomputers and their cost prohibited many schools from offering CAD instruction. Today, many powerful personal computers are capable of performing the high-speed calculation and analysis required by the CAD application; however,…

A Computer-Aided Diagnosis System for Breast Cancer Combining Digital Mammography and Genomics

DTIC Science & Technology

2006-05-01

Huang, "Breast cancer diagnosis using self-organizing map for sonography." Ultrasound Med. Biol. 26, 405 (2000). 20 K. Horsch, M.L. Giger, L.A. Venta ...L.A. Venta , "Performance of computer-aided diagnosis in the interpretation of lesions on breast sonography." Acad Radiol 11, 272 (2004). 22 W. Chen...418. 27. Horsch K, Giger ML, Vyborny CJ, Venta LA. Performance of computer-aided diagnosis in the interpretation of lesions on breast sonography

Computer-aided design of the RF-cavity for a high-power S-band klystron

NASA Astrophysics Data System (ADS)

Kant, D.; Bandyopadhyay, A. K.; Pal, D.; Meena, R.; Nangru, S. C.; Joshi, L. M.

2012-08-01

This article describes the computer-aided design of the RF-cavity for a S-band klystron operating at 2856 MHz. State-of-the-art electromagnetic simulation tools SUPERFISH, CST Microwave studio, HFSS and MAGIC have been used for cavity design. After finalising the geometrical details of the cavity through simulation, it has been fabricated and characterised through cold testing. Detailed results of the computer-aided simulation and cold measurements are presented in this article.

Computer aided design of monolithic microwave and millimeter wave integrated circuits and subsystems

NASA Astrophysics Data System (ADS)

Ku, Walter H.; Gang, Guan-Wan; He, J. Q.; Ichitsubo, I.

1988-05-01

This final technical report presents results on the computer aided design of monolithic microwave and millimeter wave integrated circuits and subsystems. New results include analytical and computer aided device models of GaAs MESFETs and HEMTs or MODFETs, new synthesis techniques for monolithic feedback and distributed amplifiers and a new nonlinear CAD program for MIMIC called CADNON. This program incorporates the new MESFET and HEMT model and has been successfully applied to the design of monolithic millimeter-wave mixers.

An Interactive Computer Aided Design and Analysis Package.

DTIC Science & Technology

1986-03-01

Al-A167 114 AN INTERACTIVE COMPUTER AIDED DESIGN MUD ANAILYSIS 1/𔃼 PACKAGE(U) NAVAL POSTGRADUATE SCHOOL NONTEREY CA T L EUALD "AR 86 UNCLSSIFIED F... SCHOOL Monterey, California DTIC .LECTE MAYOS THESIS AN INTERACTIVE COMPUTER AIDED DESIGN AND ANALYSIS PACKAGE by Terrence L. Ewald March 1986 jThesis...ORGANIZATION Naval Postgraduate School (if dAp90h81111) Naval Postgraduate School . 62A 6C. ADDRESS (0ty. State, and ZIP Code) 7b. ADDRESS (City State. and

Genalogical approaches to ethical implications of informational assimilative integrated discovery systems (AIDS) in business

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pharhizgar, K.D.; Lunce, S.E.

1994-12-31

Development of knowledge-based technological acquisition techniques and customers` information profiles are known as assimilative integrated discovery systems (AIDS) in modern organizations. These systems have access through processing to both deep and broad domains of information in modern societies. Through these systems organizations and individuals can predict future trend probabilities and events concerning their customers. AIDSs are new techniques which produce new information which informants can use without the help of the knowledge sources because of the existence of highly sophisticated computerized networks. This paper has analyzed the danger and side effects of misuse of information through the illegal, unethical andmore » immoral access to the data-base in an integrated and assimilative information system as described above. Cognivistic mapping, pragmatistic informational design gathering, and holistic classifiable and distributive techniques are potentially abusive systems whose outputs can be easily misused by businesses when researching the firm`s customers.« less

Computer Aided Creativity.

ERIC Educational Resources Information Center

Proctor, Tony

1988-01-01

Explores the conceptual components of a computer program designed to enhance creative thinking and reviews software that aims to stimulate creative thinking. Discusses BRAIN and ORACLE, programs intended to aid in creative problem solving. (JOW)

Prerequisites for Computer-Aided Cognitive Rehabilitation.

ERIC Educational Resources Information Center

Legrand, Colette

1989-01-01

This paper describes computer-aided cognitive rehabilitation for mentally deficient persons. It lists motor, cognitive, emotional, and educational prerequisites to such rehabilitation and states advantages and disadvantages in using the prerequisites. (JDD)

Micro and Mainframe Computer Models for Improved Planning in Awarding Financial Aid to Disadvantaged Students.

ERIC Educational Resources Information Center

Attinasi, Louis C., Jr.; Fenske, Robert H.

1988-01-01

Two computer models used at Arizona State University recognize the tendency of students from low-income and minority backgrounds to apply for assistance late in the funding cycle. They permit administrators to project the amount of aid needed by such students. The Financial Aid Computerized Tracking System is described. (Author/MLW)

A Computer-Based, Interactive Videodisc Job Aid and Expert System for Electron Beam Lithography Integration and Diagnostic Procedures.

ERIC Educational Resources Information Center

Stevenson, Kimberly

This master's thesis describes the development of an expert system and interactive videodisc computer-based instructional job aid used for assisting in the integration of electron beam lithography devices. Comparable to all comprehensive training, expert system and job aid development require a criterion-referenced systems approach treatment to…

Incorporation of CAD/CAM Restoration Into Navy Dentistry

DTIC Science & Technology

2017-09-26

CAD/CAM Computer-aided design /Computer-assisted manufacturing CDT Common Dental Terminology DENCAS Dental Common Access System DTF Dental...to reduce avoidable dental emergencies for deployed sailors and marines. Dental Computer-aided design /Computer-assisted manufacturing (CAD/CAM...report will review and evaluate the placement rate by Navy dentists of digitally fabricated in-office ceramic restorations compared to traditional direct

The Role of Computer-Aided Instruction in Science Courses and the Relevant Misconceptions of Pre-Service Teachers

ERIC Educational Resources Information Center

Aksakalli, Ayhan; Turgut, Umit; Salar, Riza

2016-01-01

This research aims to investigate the ways in which pre-service physics teachers interact with computers, which, as an indispensable means of today's technology, are of major value in education and training, and to identify any misconceptions said teachers may have about computer-aided instruction. As part of the study, computer-based physics…

Student Performance in Computer-Assisted Instruction in Programming.

ERIC Educational Resources Information Center

Friend, Jamesine E.; And Others

A computer-assisted instructional system to teach college students the computer language, AID (Algebraic Interpretive Dialogue), two control programs, and data collected by the two control programs are described. It was found that although first response errors were often those of AID syntax, such errors were easily corrected. Secondly, while…

Cooperation Support in Computer-Aided Authoring and Learning.

ERIC Educational Resources Information Center

Muhlhauser, Max; Rudebusch, Tom

This paper discusses the use of Computer Supported Cooperative Work (CSCW) techniques for computer-aided learning (CAL); the work was started in the context of project Nestor, a joint effort of German universities about cooperative multimedia authoring/learning environments. There are four major categories of cooperation for CAL: author/author,…

Computer-Assisted Instruction: One Aid for Teachers of Reading.

ERIC Educational Resources Information Center

Rauch, Margaret; Samojeden, Elizabeth

Computer assisted instruction (CAI), an instructional system with direct interaction between the student and the computer, can be a valuable aid for presenting new concepts, for reinforcing of selective skills, and for individualizing instruction. The advantages CAI provides include self-paced learning, more efficient allocation of classroom time,…

Computational methods for 2D materials: discovery, property characterization, and application design.

PubMed

Paul, J T; Singh, A K; Dong, Z; Zhuang, H; Revard, B C; Rijal, B; Ashton, M; Linscheid, A; Blonsky, M; Gluhovic, D; Guo, J; Hennig, R G

2017-11-29

The discovery of two-dimensional (2D) materials comes at a time when computational methods are mature and can predict novel 2D materials, characterize their properties, and guide the design of 2D materials for applications. This article reviews the recent progress in computational approaches for 2D materials research. We discuss the computational techniques and provide an overview of the ongoing research in the field. We begin with an overview of known 2D materials, common computational methods, and available cyber infrastructures. We then move onto the discovery of novel 2D materials, discussing the stability criteria for 2D materials, computational methods for structure prediction, and interactions of monolayers with electrochemical and gaseous environments. Next, we describe the computational characterization of the 2D materials' electronic, optical, magnetic, and superconducting properties and the response of the properties under applied mechanical strain and electrical fields. From there, we move on to discuss the structure and properties of defects in 2D materials, and describe methods for 2D materials device simulations. We conclude by providing an outlook on the needs and challenges for future developments in the field of computational research for 2D materials.

Computational methods for 2D materials: discovery, property characterization, and application design

NASA Astrophysics Data System (ADS)

Paul, J. T.; Singh, A. K.; Dong, Z.; Zhuang, H.; Revard, B. C.; Rijal, B.; Ashton, M.; Linscheid, A.; Blonsky, M.; Gluhovic, D.; Guo, J.; Hennig, R. G.

2017-11-01

The discovery of two-dimensional (2D) materials comes at a time when computational methods are mature and can predict novel 2D materials, characterize their properties, and guide the design of 2D materials for applications. This article reviews the recent progress in computational approaches for 2D materials research. We discuss the computational techniques and provide an overview of the ongoing research in the field. We begin with an overview of known 2D materials, common computational methods, and available cyber infrastructures. We then move onto the discovery of novel 2D materials, discussing the stability criteria for 2D materials, computational methods for structure prediction, and interactions of monolayers with electrochemical and gaseous environments. Next, we describe the computational characterization of the 2D materials’ electronic, optical, magnetic, and superconducting properties and the response of the properties under applied mechanical strain and electrical fields. From there, we move on to discuss the structure and properties of defects in 2D materials, and describe methods for 2D materials device simulations. We conclude by providing an outlook on the needs and challenges for future developments in the field of computational research for 2D materials.

KSC-2012-2116

NASA Image and Video Library

2012-04-14

CAPE CANAVERAL, Fla. – At the Shuttle Landing Facility, or SLF, at NASA’s Kennedy Space Center in Florida, space shuttle Discovery rolls past the Shuttle Carrier Aircraft with which it will be mated. Discovery will be hoisted onto the SCA with the aid of a mate-demate device. The SCA, a modified Boeing 747 jet airliner, is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on permanent public display in the Smithsonian's National Air and Space Museum Steven F. Udvar-Hazy Center. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Jim Grossmann

Corpus of High School Academic Texts (COHAT): Data-Driven, Computer Assisted Discovery in Learning Academic English

ERIC Educational Resources Information Center

Bohát, Róbert; Rödlingová, Beata; Horáková, Nina

2015-01-01

Corpus of High School Academic Texts (COHAT), currently of 150,000+ words, aims to make academic language instruction a more data-driven and student-centered discovery learning as a special type of Computer-Assisted Language Learning (CALL), emphasizing students' critical thinking and metacognition. Since 2013, high school English as an additional…

The Goal Specificity Effect on Strategy Use and Instructional Efficiency during Computer-Based Scientific Discovery Learning

ERIC Educational Resources Information Center

Kunsting, Josef; Wirth, Joachim; Paas, Fred

2011-01-01

Using a computer-based scientific discovery learning environment on buoyancy in fluids we investigated the "effects of goal specificity" (nonspecific goals vs. specific goals) for two goal types (problem solving goals vs. learning goals) on "strategy use" and "instructional efficiency". Our empirical findings close an important research gap,…

KSC-2012-2060

NASA Image and Video Library

2012-04-14

CAPE CANAVERAL, Fla. – Preparations are under way to tow space shuttle Discovery to the Shuttle Landing Facility, or SLF, at NASA’s Kennedy Space Center in Florida. Discovery was in storage in the Vehicle Assembly Building’s high bay 4 awaiting departure from Kennedy’s Launch Complex 39 area for the final time. At the SLF, Discovery will be hoisted onto a Shuttle Carrier Aircraft, or SCA, with the aid of a mate-demate device. The SCA, a modified Boeing 747 jet airliner, is scheduled to transport Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on permanent public display in the Smithsonian's National Air and Space Museum Steven F. Udvar-Hazy Center. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Kim Shiflett

Computer-aided design of high-frequency transistor amplifiers.

NASA Technical Reports Server (NTRS)

Hsieh, C.-C.; Chan, S.-P.

1972-01-01

A systematic step-by-step computer-aided procedure for designing high-frequency transistor amplifiers is described. The technique makes it possible to determine the optimum source impedance which gives a minimum noise figure.

A bioinformatics knowledge discovery in text application for grid computing

PubMed Central

Castellano, Marcello; Mastronardi, Giuseppe; Bellotti, Roberto; Tarricone, Gianfranco

2009-01-01

Background A fundamental activity in biomedical research is Knowledge Discovery which has the ability to search through large amounts of biomedical information such as documents and data. High performance computational infrastructures, such as Grid technologies, are emerging as a possible infrastructure to tackle the intensive use of Information and Communication resources in life science. The goal of this work was to develop a software middleware solution in order to exploit the many knowledge discovery applications on scalable and distributed computing systems to achieve intensive use of ICT resources. Methods The development of a grid application for Knowledge Discovery in Text using a middleware solution based methodology is presented. The system must be able to: perform a user application model, process the jobs with the aim of creating many parallel jobs to distribute on the computational nodes. Finally, the system must be aware of the computational resources available, their status and must be able to monitor the execution of parallel jobs. These operative requirements lead to design a middleware to be specialized using user application modules. It included a graphical user interface in order to access to a node search system, a load balancing system and a transfer optimizer to reduce communication costs. Results A middleware solution prototype and the performance evaluation of it in terms of the speed-up factor is shown. It was written in JAVA on Globus Toolkit 4 to build the grid infrastructure based on GNU/Linux computer grid nodes. A test was carried out and the results are shown for the named entity recognition search of symptoms and pathologies. The search was applied to a collection of 5,000 scientific documents taken from PubMed. Conclusion In this paper we discuss the development of a grid application based on a middleware solution. It has been tested on a knowledge discovery in text process to extract new and useful information about symptoms and pathologies from a large collection of unstructured scientific documents. As an example a computation of Knowledge Discovery in Database was applied on the output produced by the KDT user module to extract new knowledge about symptom and pathology bio-entities. PMID:19534749

A bioinformatics knowledge discovery in text application for grid computing.

PubMed

Castellano, Marcello; Mastronardi, Giuseppe; Bellotti, Roberto; Tarricone, Gianfranco

2009-06-16

A fundamental activity in biomedical research is Knowledge Discovery which has the ability to search through large amounts of biomedical information such as documents and data. High performance computational infrastructures, such as Grid technologies, are emerging as a possible infrastructure to tackle the intensive use of Information and Communication resources in life science. The goal of this work was to develop a software middleware solution in order to exploit the many knowledge discovery applications on scalable and distributed computing systems to achieve intensive use of ICT resources. The development of a grid application for Knowledge Discovery in Text using a middleware solution based methodology is presented. The system must be able to: perform a user application model, process the jobs with the aim of creating many parallel jobs to distribute on the computational nodes. Finally, the system must be aware of the computational resources available, their status and must be able to monitor the execution of parallel jobs. These operative requirements lead to design a middleware to be specialized using user application modules. It included a graphical user interface in order to access to a node search system, a load balancing system and a transfer optimizer to reduce communication costs. A middleware solution prototype and the performance evaluation of it in terms of the speed-up factor is shown. It was written in JAVA on Globus Toolkit 4 to build the grid infrastructure based on GNU/Linux computer grid nodes. A test was carried out and the results are shown for the named entity recognition search of symptoms and pathologies. The search was applied to a collection of 5,000 scientific documents taken from PubMed. In this paper we discuss the development of a grid application based on a middleware solution. It has been tested on a knowledge discovery in text process to extract new and useful information about symptoms and pathologies from a large collection of unstructured scientific documents. As an example a computation of Knowledge Discovery in Database was applied on the output produced by the KDT user module to extract new knowledge about symptom and pathology bio-entities.

From GRID to gridlock: the relationship between scientific biomedical breakthroughs and HIV/AIDS policy in the US Congress.

PubMed

Platt, Matthew B; Platt, Manu O

2013-11-27

From the travel ban on people living with HIV (PLHIV) to resistance to needle exchange programmes, there are many examples where policy responses to HIV/AIDS in the United States seem divorced from behavioural, public health and sociological evidence. At its root, however, the unknowns about HIV/AIDS lie at biomedical science, and scientific researchers have made tremendous progress over the past 30 years of the epidemic by using antiretroviral therapy to increase the life expectancy of PLHIV almost to the same level as non-infected individuals; but a relationship between biomedical science discoveries and congressional responses to HIV/AIDS has not been studied. Using quantitative approaches, we directly examine the hypothesis that progress in HIV/AIDS biomedical science discoveries would have a correlative relationship with congressional response to HIV/AIDS from 1981 to 2010. This study used original data on every bill introduced, hearing held and law passed by the US Congress relating to HIV/AIDS over 30 years (1981-2010). We combined congressional data with the most cited and impactful biomedical research scientific publications over the same time period as a metric of biomedical science breakthroughs. Correlations between congressional policy and biomedical research were then analyzed at the aggregate and individual levels. Biomedical research advancements helped shape both the level and content of bill sponsorship on HIV/AIDS, but they had no effect on other stages of the legislative process. Examination of the content of bills and biomedical research indicated that science helped transform HIV/AIDS bill sponsorship from a niche concern of liberal Democrats to a bipartisan coalition when Republicans became the majority party. The trade-off for that expansion has been an emphasis on the global epidemic to the detriment of domestic policies and programmes. Breakthroughs in biomedical science did associate with the number and types of HIV/AIDS bills introduced in Congress, but that relationship did not extend to the passage of laws or to hearings. When science matters, it cannot be separated from political considerations. An important implication of our work has been the depoliticizing role that science can play. Scientific breakthroughs helped to transform HIV/AIDS policy from a niche of liberal Democrats into bipartisan support for the global fight against the disease.

From GRID to gridlock: the relationship between scientific biomedical breakthroughs and HIV/AIDS policy in the US Congress

PubMed Central

Platt, Matthew B; Platt, Manu O

2013-01-01

Introduction From the travel ban on people living with HIV (PLHIV) to resistance to needle exchange programmes, there are many examples where policy responses to HIV/AIDS in the United States seem divorced from behavioural, public health and sociological evidence. At its root, however, the unknowns about HIV/AIDS lie at biomedical science, and scientific researchers have made tremendous progress over the past 30 years of the epidemic by using antiretroviral therapy to increase the life expectancy of PLHIV almost to the same level as non-infected individuals; but a relationship between biomedical science discoveries and congressional responses to HIV/AIDS has not been studied. Using quantitative approaches, we directly examine the hypothesis that progress in HIV/AIDS biomedical science discoveries would have a correlative relationship with congressional response to HIV/AIDS from 1981 to 2010. Methods This study used original data on every bill introduced, hearing held and law passed by the US Congress relating to HIV/AIDS over 30 years (1981–2010). We combined congressional data with the most cited and impactful biomedical research scientific publications over the same time period as a metric of biomedical science breakthroughs. Correlations between congressional policy and biomedical research were then analyzed at the aggregate and individual levels. Results Biomedical research advancements helped shape both the level and content of bill sponsorship on HIV/AIDS, but they had no effect on other stages of the legislative process. Examination of the content of bills and biomedical research indicated that science helped transform HIV/AIDS bill sponsorship from a niche concern of liberal Democrats to a bipartisan coalition when Republicans became the majority party. The trade-off for that expansion has been an emphasis on the global epidemic to the detriment of domestic policies and programmes. Conclusions Breakthroughs in biomedical science did associate with the number and types of HIV/AIDS bills introduced in Congress, but that relationship did not extend to the passage of laws or to hearings. When science matters, it cannot be separated from political considerations. An important implication of our work has been the depoliticizing role that science can play. Scientific breakthroughs helped to transform HIV/AIDS policy from a niche of liberal Democrats into bipartisan support for the global fight against the disease. PMID:24286556

Three-dimensional surgical simulation.

PubMed

Cevidanes, Lucia H C; Tucker, Scott; Styner, Martin; Kim, Hyungmin; Chapuis, Jonas; Reyes, Mauricio; Proffit, William; Turvey, Timothy; Jaskolka, Michael

2010-09-01

In this article, we discuss the development of methods for computer-aided jaw surgery, which allows us to incorporate the high level of precision necessary for transferring virtual plans into the operating room. We also present a complete computer-aided surgery system developed in close collaboration with surgeons. Surgery planning and simulation include construction of 3-dimensional surface models from cone-beam computed tomography, dynamic cephalometry, semiautomatic mirroring, interactive cutting of bone, and bony segment repositioning. A virtual setup can be used to manufacture positioning splints for intraoperative guidance. The system provides further intraoperative assistance with a computer display showing jaw positions and 3-dimensional positioning guides updated in real time during the surgical procedure. The computer-aided surgery system aids in dealing with complex cases with benefits for the patient, with surgical practice, and for orthodontic finishing. Advanced software tools for diagnosis and treatment planning allow preparation of detailed operative plans, osteotomy repositioning, bone reconstructions, surgical resident training, and assessing the difficulties of the surgical procedures before the surgery. Computer-aided surgery can make the elaboration of the surgical plan a more flexible process, increase the level of detail and accuracy of the plan, yield higher operative precision and control, and enhance documentation of cases. 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Sustainable design and manufacturing of multifunctional polymer nanocomposite coatings: A multiscale systems approach

NASA Astrophysics Data System (ADS)

Xiao, Jie

Polymer nanocomposites have a great potential to be a dominant coating material in a wide range of applications in the automotive, aerospace, ship-making, construction, and pharmaceutical industries. However, how to realize design sustainability of this type of nanostructured materials and how to ensure the true optimality of the product quality and process performance in coating manufacturing remain as a mountaintop area. The major challenges arise from the intrinsic multiscale nature of the material-process-product system and the need to manipulate the high levels of complexity and uncertainty in design and manufacturing processes. This research centers on the development of a comprehensive multiscale computational methodology and a computer-aided tool set that can facilitate multifunctional nanocoating design and application from novel function envisioning and idea refinement, to knowledge discovery and design solution derivation, and further to performance testing in industrial applications and life cycle analysis. The principal idea is to achieve exceptional system performance through concurrent characterization and optimization of materials, product and associated manufacturing processes covering a wide range of length and time scales. Multiscale modeling and simulation techniques ranging from microscopic molecular modeling to classical continuum modeling are seamlessly coupled. The tight integration of different methods and theories at individual scales allows the prediction of macroscopic coating performance from the fundamental molecular behavior. Goal-oriented design is also pursued by integrating additional methods for bio-inspired dynamic optimization and computational task management that can be implemented in a hierarchical computing architecture. Furthermore, multiscale systems methodologies are developed to achieve the best possible material application towards sustainable manufacturing. Automotive coating manufacturing, that involves paint spay and curing, is specifically discussed in this dissertation. Nevertheless, the multiscale considerations for sustainable manufacturing, the novel concept of IPP control, and the new PPDE-based optimization method are applicable to other types of manufacturing, e.g., metal coating development through electroplating. It is demonstrated that the methodological development in this dissertation can greatly facilitate experimentalists in novel material invention and new knowledge discovery. At the same time, they can provide scientific guidance and reveal various new opportunities and effective strategies for sustainable manufacturing.

A sexually transmitted disease: History of AIDS through philately.

PubMed

Vatanoğlu, Emine Elif; Ataman, Ahmet Doğan

2011-01-01

AIDS has become the new plague; a disease that is not only physically and psychologically debilitating, but culturally and socially devastating as well. Like the plague, AIDS has caused fear, prejudice and even panic in society. Although there are remarkable improvements in the diagnosis and treatment of the disease, AIDS continues its grim passage around the globe. After a slight downturn in the early 1990's, it then returned with a vengeance. By the end of the 20(th) century, AIDS was reliably estimated to have caused over 20 million deaths throughout the world. At the same time, 40 million people were estimated to be HIV positive. This paper provides an overview of the history of AIDS, including the discovery and its progress in the world through philately. Philately is the study of stamps and postal history and other related items. Philately involves more than just stamp collecting, it contains the study of the design and educational impact of a philatelic material. We have presented AIDS stamps produced world-wide to emphasize the history of AIDS.

Space Spurred Computer Graphics

NASA Technical Reports Server (NTRS)

1983-01-01

Dicomed Corporation was asked by NASA in the early 1970s to develop processing capabilities for recording images sent from Mars by Viking spacecraft. The company produced a film recorder which increased the intensity levels and the capability for color recording. This development led to a strong technology base resulting in sophisticated computer graphics equipment. Dicomed systems are used to record CAD (computer aided design) and CAM (computer aided manufacturing) equipment, to update maps and produce computer generated animation.

A Novel Computer-Aided Design/Computer-Assisted Manufacture Method for One-Piece Removable Partial Denture and Evaluation of Fit.

PubMed

Ye, Hongqiang; Li, Xinxin; Wang, Guanbo; Kang, Jing; Liu, Yushu; Sun, Yuchun; Zhou, Yongsheng

2018-02-15

To investigate a computer-aided design/computer-aided manufacturing (CAD/CAM) process for producing one-piece removable partial dentures (RPDs) and to evaluate their fits in vitro. A total of 15 one-piece RPDs were designed using dental CAD and reverse engineering software and then fabricated with polyetheretherketone (PEEK) using CAM. The gaps between RPDs and casts were measured and compared with traditional cast framework RPDs. Gaps were lower for one-piece PEEK RPDs compared to traditional RPDs. One-piece RPDs can be manufactured by CAD/CAM, and their fits were better than those of traditional RPDs.

STS-103 Crew Training

NASA Technical Reports Server (NTRS)

1999-01-01

The Hubble Space Telescope (HST) team is preparing for NASA's third scheduled service call to Hubble. This mission, STS-103, will launch from Kennedy Space Center aboard the Space Shuttle Discovery. The seven flight crew members are Commander Curtis L. Brown, Pilot Scott J. Kelly, European Space Agency (ESA) astronaut Jean-Francois Clervoy who will join space walkers Steven L. Smith, C. Michael Foale, John M. Grunsfeld, and ESA astronaut Claude Nicollier. The objectives of the HST Third Servicing Mission (SM3A) are to replace the telescope's six gyroscopes, a Fine-Guidance Sensor, an S-Band Single Access Transmitter, a spare solid-state recorder and a high-voltage/temperature kit for protecting the batteries from overheating. In addition, the crew plans to install an advanced computer that is 20 times faster and has six times the memory of the current Hubble Space Telescope computer. To prepare for these extravehicular activities (EVAs), the SM3A astronauts participated in Crew Familiarization sessions with the actual SM3A flight hardware. During these sessions the crew spent long hours rehearsing their space walks in the Guidance Navigation Simulator and NBL (Neutral Buoyancy Laboratory). Using space gloves, flight Space Support Equipment (SSE), and Crew Aids and Tools (CATs), the astronauts trained with and verified flight orbital replacement unit (ORU) hardware. The crew worked with a number of trainers and simulators, such as the High Fidelity Mechanical Simulator, Guidance Navigation Simulator, System Engineering Simulator, the Aft Shroud Door Trainer, the Forward Shell/Light Shield Simulator, and the Support Systems Module Bay Doors Simulator. They also trained and verified the flight Orbital Replacement Unit Carrier (ORUC) and its ancillary hardware. Discovery's planned 10-day flight is scheduled to end with a night landing at Kennedy.

Discovering chemistry with an ab initio nanoreactor

DOE PAGES

Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert; ...

2014-11-02

Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provides detailed physical insight. While theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor – a highly accelerated, first-principles molecular dynamics simulation of chemical reactions that discovers new molecules and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor we show new pathways for glycine synthesis frommore » primitive compounds proposed to exist on the early Earth, providing new insight into the classic Urey-Miller experiment. Ultimately, these results highlight the emergence of theoretical and computational chemistry as a tool for discovery in addition to its traditional role of interpreting experimental findings.« less

Discovering chemistry with an ab initio nanoreactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert

Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provides detailed physical insight. While theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor – a highly accelerated, first-principles molecular dynamics simulation of chemical reactions that discovers new molecules and mechanisms without preordained reaction coordinates or elementary steps. Using the nanoreactor we show new pathways for glycine synthesis frommore » primitive compounds proposed to exist on the early Earth, providing new insight into the classic Urey-Miller experiment. Ultimately, these results highlight the emergence of theoretical and computational chemistry as a tool for discovery in addition to its traditional role of interpreting experimental findings.« less

Effect of Computer-Presented Organizational/Memory Aids on Problem Solving Behavior.

ERIC Educational Resources Information Center

Steinberg, Esther R.; And Others

This research studied the effects of computer-presented organizational/memory aids on problem solving behavior. The aids were either matrix or verbal charts shown on the display screen next to the problem. The 104 college student subjects were randomly assigned to one of the four conditions: type of chart (matrix or verbal chart) and use of charts…

Programming Design Guide for Computer Implementation of Job Aid for Selecting Instructional Setting. Final Report.

ERIC Educational Resources Information Center

Schulz, Russel E.; And Others

This Programming Design Guide (PDG) was developed to permit the offline Job Aid for Selecting Instructional Setting, which is one of 13 job aids presently available for use with the Instructional Systems Development (ISD) model, to be available in an inquiry-type, online version. It is intended to provide computer programmers with all of the…

Teaching Advance Care Planning to Medical Students with a Computer-Based Decision Aid

PubMed Central

Levi, Benjamin H.

2013-01-01

Discussing end-of-life decisions with cancer patients is a crucial skill for physicians. This article reports findings from a pilot study evaluating the effectiveness of a computer-based decision aid for teaching medical students about advance care planning. Second-year medical students at a single medical school were randomized to use a standard advance directive or a computer-based decision aid to help patients with advance care planning. Students' knowledge, skills, and satisfaction were measured by self-report; their performance was rated by patients. 121/133 (91%) of students participated. The Decision-Aid Group (n=60) outperformed the Standard Group (n=61) in terms of students´ knowledge (p<0.01), confidence in helping patients with advance care planning (p<0.01), knowledge of what matters to patients (p=0.05), and satisfaction with their learning experience (p<0.01). Likewise, patients in the Decision Aid Group were more satisfied with the advance care planning method (p<0.01) and with several aspects of student performance. Use of a computer-based decision aid may be an effective way to teach medical students how to discuss advance care planning with cancer patients. PMID:20632222

Evaluation of direct and indirect additive manufacture of maxillofacial prostheses.

PubMed

Eggbeer, Dominic; Bibb, Richard; Evans, Peter; Ji, Lu

2012-09-01

The efficacy of computer-aided technologies in the design and manufacture of maxillofacial prostheses has not been fully proven. This paper presents research into the evaluation of direct and indirect additive manufacture of a maxillofacial prosthesis against conventional laboratory-based techniques. An implant/magnet-retained nasal prosthesis case from a UK maxillofacial unit was selected as a case study. A benchmark prosthesis was fabricated using conventional laboratory-based techniques for comparison against additive manufactured prostheses. For the computer-aided workflow, photogrammetry, computer-aided design and additive manufacture (AM) methods were evaluated in direct prosthesis body fabrication and indirect production using an additively manufactured mould. Qualitative analysis of position, shape, colour and edge quality was undertaken. Mechanical testing to ISO standards was also used to compare the silicone rubber used in the conventional prosthesis with the AM material. Critical evaluation has shown that utilising a computer-aided work-flow can produce a prosthesis body that is comparable to that produced using existing best practice. Technical limitations currently prevent the direct fabrication method demonstrated in this paper from being clinically viable. This research helps prosthesis providers understand the application of a computer-aided approach and guides technology developers and researchers to address the limitations identified.

Computational modelling of the impact of AIDS on business.

PubMed

Matthews, Alan P

2007-07-01

An overview of computational modelling of the impact of AIDS on business in South Africa, with a detailed description of the AIDS Projection Model (APM) for companies, developed by the author, and suggestions for further work. Computational modelling of the impact of AIDS on business in South Africa requires modelling of the epidemic as a whole, and of its impact on a company. This paper gives an overview of epidemiological modelling, with an introduction to the Actuarial Society of South Africa (ASSA) model, the most widely used such model for South Africa. The APM produces projections of HIV prevalence, new infections, and AIDS mortality on a company, based on the anonymous HIV testing of company employees, and projections from the ASSA model. A smoothed statistical model of the prevalence test data is computed, and then the ASSA model projection for each category of employees is adjusted so that it matches the measured prevalence in the year of testing. FURTHER WORK: Further techniques that could be developed are microsimulation (representing individuals in the computer), scenario planning for testing strategies, and models for the business environment, such as models of entire sectors, and mapping of HIV prevalence in time and space, based on workplace and community data.

Exploration of a physiologically-inspired hearing-aid algorithm using a computer model mimicking impaired hearing.

PubMed

Jürgens, Tim; Clark, Nicholas R; Lecluyse, Wendy; Meddis, Ray

2016-01-01

To use a computer model of impaired hearing to explore the effects of a physiologically-inspired hearing-aid algorithm on a range of psychoacoustic measures. A computer model of a hypothetical impaired listener's hearing was constructed by adjusting parameters of a computer model of normal hearing. Absolute thresholds, estimates of compression, and frequency selectivity (summarized to a hearing profile) were assessed using this model with and without pre-processing the stimuli by a hearing-aid algorithm. The influence of different settings of the algorithm on the impaired profile was investigated. To validate the model predictions, the effect of the algorithm on hearing profiles of human impaired listeners was measured. A computer model simulating impaired hearing (total absence of basilar membrane compression) was used, and three hearing-impaired listeners participated. The hearing profiles of the model and the listeners showed substantial changes when the test stimuli were pre-processed by the hearing-aid algorithm. These changes consisted of lower absolute thresholds, steeper temporal masking curves, and sharper psychophysical tuning curves. The hearing-aid algorithm affected the impaired hearing profile of the model to approximate a normal hearing profile. Qualitatively similar results were found with the impaired listeners' hearing profiles.

Program Aids Specification Of Multiple-Block Grids

NASA Technical Reports Server (NTRS)

Sorenson, R. L.; Mccann, K. M.

1993-01-01

3DPREP computer program aids specification of multiple-block computational grids. Highly interactive graphical preprocessing program designed for use on powerful graphical scientific computer workstation. Divided into three main parts, each corresponding to principal graphical-and-alphanumerical display. Relieves user of some burden of collecting and formatting many data needed to specify blocks and grids, and prepares input data for NASA's 3DGRAPE grid-generating computer program.

Computer Aided Phenomenography: The Role of Leximancer Computer Software in Phenomenographic Investigation

ERIC Educational Resources Information Center

Penn-Edwards, Sorrel

2010-01-01

The qualitative research methodology of phenomenography has traditionally required a manual sorting and analysis of interview data. In this paper I explore a potential means of streamlining this procedure by considering a computer aided process not previously reported upon. Two methods of lexicological analysis, manual and automatic, were examined…

Computer-Aided College Algebra: Learning Components that Students Find Beneficial

ERIC Educational Resources Information Center

Aichele, Douglas B.; Francisco, Cynthia; Utley, Juliana; Wescoatt, Benjamin

2011-01-01

A mixed-method study was conducted during the Fall 2008 semester to better understand the experiences of students participating in computer-aided instruction of College Algebra using the software MyMathLab. The learning environment included a computer learning system for the majority of the instruction, a support system via focus groups (weekly…

Computer Aided Instruction: A Study of Student Evaluations and Academic Performance

ERIC Educational Resources Information Center

Collins, David; Deck, Alan; McCrickard, Myra

2008-01-01

Computer aided instruction (CAI) encompasses a broad range of computer technologies that supplement the classroom learning environment and can dramatically increase a student's access to information. Criticism of CAI generally focuses on two issues: it lacks an adequate foundation in educational theory and the software is difficult to implement…

Using Computer Graphics in the 90's.

ERIC Educational Resources Information Center

Towne, Violet A.

Computer-Aided Design, a hands-on program for public school teachers, was first offered in the summer of 1987 as an outgrowth of a 1986 robotics training program. Area technology teachers needed computer-aided design (CAD) training because of a New York State Education system transition from the industrial arts curriculum to a new curriculum in…

Using Computer-Aided Instruction to Support the Systematic Practice of Phonological Skills in Beginning Readers

ERIC Educational Resources Information Center

Wild, Mary

2009-01-01

The paper reports the results of a randomised control trial investigating the use of computer-aided instruction (CAI) for practising phonological awareness skills with beginning readers. Two intervention groups followed the same phonological awareness programme: one group undertook practice exercises using a computer and the other group undertook…

The Impact of Software on Associate Degree Programs in Electronic Engineering Technology.

ERIC Educational Resources Information Center

Hata, David M.

1986-01-01

Assesses the range and extent of computer assisted instruction software available in electronic engineering technology education. Examines the need for software skills in four areas: (1) high-level languages; (2) assembly language; (3) computer-aided engineering; and (4) computer-aided instruction. Outlines strategies for the future in three…

Computer Code Aids Design Of Wings

NASA Technical Reports Server (NTRS)

Carlson, Harry W.; Darden, Christine M.

1993-01-01

AERO2S computer code developed to aid design engineers in selection and evaluation of aerodynamically efficient wing/canard and wing/horizontal-tail configurations that includes simple hinged-flap systems. Code rapidly estimates longitudinal aerodynamic characteristics of conceptual airplane lifting-surface arrangements. Developed in FORTRAN V on CDC 6000 computer system, and ported to MS-DOS environment.

Computer Aided Grid Interface: An Interactive CFD Pre-Processor

NASA Technical Reports Server (NTRS)

Soni, Bharat K.

1997-01-01

NASA maintains an applications oriented computational fluid dynamics (CFD) efforts complementary to and in support of the aerodynamic-propulsion design and test activities. This is especially true at NASA/MSFC where the goal is to advance and optimize present and future liquid-fueled rocket engines. Numerical grid generation plays a significant role in the fluid flow simulations utilizing CFD. An overall goal of the current project was to develop a geometry-grid generation tool that will help engineers, scientists and CFD practitioners to analyze design problems involving complex geometries in a timely fashion. This goal is accomplished by developing the CAGI: Computer Aided Grid Interface system. The CAGI system is developed by integrating CAD/CAM (Computer Aided Design/Computer Aided Manufacturing) geometric system output and/or Initial Graphics Exchange Specification (IGES) files (including all the NASA-IGES entities), geometry manipulations and generations associated with grid constructions, and robust grid generation methodologies. This report describes the development process of the CAGI system.

Computer Aided Grid Interface: An Interactive CFD Pre-Processor

NASA Technical Reports Server (NTRS)

Soni, Bharat K.

1996-01-01

NASA maintains an applications oriented computational fluid dynamics (CFD) efforts complementary to and in support of the aerodynamic-propulsion design and test activities. This is especially true at NASA/MSFC where the goal is to advance and optimize present and future liquid-fueled rocket engines. Numerical grid generation plays a significant role in the fluid flow simulations utilizing CFD. An overall goal of the current project was to develop a geometry-grid generation tool that will help engineers, scientists and CFD practitioners to analyze design problems involving complex geometries in a timely fashion. This goal is accomplished by developing the Computer Aided Grid Interface system (CAGI). The CAGI system is developed by integrating CAD/CAM (Computer Aided Design/Computer Aided Manufacturing) geometric system output and / or Initial Graphics Exchange Specification (IGES) files (including all the NASA-IGES entities), geometry manipulations and generations associated with grid constructions, and robust grid generation methodologies. This report describes the development process of the CAGI system.

Meta Data Mining in Earth Remote Sensing Data Archives

NASA Astrophysics Data System (ADS)

Davis, B.; Steinwand, D.

2014-12-01

Modern search and discovery tools for satellite based remote sensing data are often catalog based and rely on query systems which use scene- (or granule-) based meta data for those queries. While these traditional catalog systems are often robust, very little has been done in the way of meta data mining to aid in the search and discovery process. The recently coined term "Big Data" can be applied in the remote sensing world's efforts to derive information from the vast data holdings of satellite based land remote sensing data. Large catalog-based search and discovery systems such as the United States Geological Survey's Earth Explorer system and the NASA Earth Observing System Data and Information System's Reverb-ECHO system provide comprehensive access to these data holdings, but do little to expose the underlying scene-based meta data. These catalog-based systems are extremely flexible, but are manually intensive and often require a high level of user expertise. Exposing scene-based meta data to external, web-based services can enable machine-driven queries to aid in the search and discovery process. Furthermore, services which expose additional scene-based content data (such as product quality information) are now available and can provide a "deeper look" into remote sensing data archives too large for efficient manual search methods. This presentation shows examples of the mining of Landsat and Aster scene-based meta data, and an experimental service using OPeNDAP to extract information from quality band from multiple granules in the MODIS archive.

Computer aided detection in prostate cancer diagnostics: A promising alternative to biopsy? A retrospective study from 104 lesions with histological ground truth.

PubMed

Thon, Anika; Teichgräber, Ulf; Tennstedt-Schenk, Cornelia; Hadjidemetriou, Stathis; Winzler, Sven; Malich, Ansgar; Papageorgiou, Ismini

2017-01-01

Prostate cancer (PCa) diagnosis by means of multiparametric magnetic resonance imaging (mpMRI) is a current challenge for the development of computer-aided detection (CAD) tools. An innovative CAD-software (Watson Elementary™) was proposed to achieve high sensitivity and specificity, as well as to allege a correlate to Gleason grade. To assess the performance of Watson Elementary™ in automated PCa diagnosis in our hospital´s database of MRI-guided prostate biopsies. The evaluation was retrospective for 104 lesions (47 PCa, 57 benign) from 79, 64.61±6.64 year old patients using 3T T2-weighted imaging, Apparent Diffusion Coefficient (ADC) maps and dynamic contrast enhancement series. Watson Elementary™ utilizes signal intensity, diffusion properties and kinetic profile to compute a proportional Gleason grade predictor, termed Malignancy Attention Index (MAI). The analysis focused on (i) the CAD sensitivity and specificity to classify suspect lesions and (ii) the MAI correlation with the histopathological ground truth. The software revealed a sensitivity of 46.80% for PCa classification. The specificity for PCa was found to be 75.43% with a positive predictive value of 61.11%, a negative predictive value of 63.23% and a false discovery rate of 38.89%. CAD classified PCa and benign lesions with equal probability (P 0.06, χ2 test). Accordingly, receiver operating characteristic analysis suggests a poor predictive value for MAI with an area under curve of 0.65 (P 0.02), which is not superior to the performance of board certified observers. Moreover, MAI revealed no significant correlation with Gleason grade (P 0.60, Pearson´s correlation). The tested CAD software for mpMRI analysis was a weak PCa biomarker in this dataset. Targeted prostate biopsy and histology remains the gold standard for prostate cancer diagnosis.

Computer aided detection in prostate cancer diagnostics: A promising alternative to biopsy? A retrospective study from 104 lesions with histological ground truth

PubMed Central

Thon, Anika; Teichgräber, Ulf; Tennstedt-Schenk, Cornelia; Hadjidemetriou, Stathis; Winzler, Sven; Malich, Ansgar

2017-01-01

Background Prostate cancer (PCa) diagnosis by means of multiparametric magnetic resonance imaging (mpMRI) is a current challenge for the development of computer-aided detection (CAD) tools. An innovative CAD-software (Watson Elementary™) was proposed to achieve high sensitivity and specificity, as well as to allege a correlate to Gleason grade. Aim/Objective To assess the performance of Watson Elementary™ in automated PCa diagnosis in our hospital´s database of MRI-guided prostate biopsies. Methods The evaluation was retrospective for 104 lesions (47 PCa, 57 benign) from 79, 64.61±6.64 year old patients using 3T T2-weighted imaging, Apparent Diffusion Coefficient (ADC) maps and dynamic contrast enhancement series. Watson Elementary™ utilizes signal intensity, diffusion properties and kinetic profile to compute a proportional Gleason grade predictor, termed Malignancy Attention Index (MAI). The analysis focused on (i) the CAD sensitivity and specificity to classify suspect lesions and (ii) the MAI correlation with the histopathological ground truth. Results The software revealed a sensitivity of 46.80% for PCa classification. The specificity for PCa was found to be 75.43% with a positive predictive value of 61.11%, a negative predictive value of 63.23% and a false discovery rate of 38.89%. CAD classified PCa and benign lesions with equal probability (P 0.06, χ2 test). Accordingly, receiver operating characteristic analysis suggests a poor predictive value for MAI with an area under curve of 0.65 (P 0.02), which is not superior to the performance of board certified observers. Moreover, MAI revealed no significant correlation with Gleason grade (P 0.60, Pearson´s correlation). Conclusion The tested CAD software for mpMRI analysis was a weak PCa biomarker in this dataset. Targeted prostate biopsy and histology remains the gold standard for prostate cancer diagnosis. PMID:29023572

Integration of lyoplate based flow cytometry and computational analysis for standardized immunological biomarker discovery.

PubMed

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R; Nestle, Frank O

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases.

Integration of Lyoplate Based Flow Cytometry and Computational Analysis for Standardized Immunological Biomarker Discovery

PubMed Central

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A. Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R.; Nestle, Frank O.

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases. PMID:23843942

Computational functional genomics-based approaches in analgesic drug discovery and repurposing.

PubMed

Lippmann, Catharina; Kringel, Dario; Ultsch, Alfred; Lötsch, Jörn

2018-06-01

Persistent pain is a major healthcare problem affecting a fifth of adults worldwide with still limited treatment options. The search for new analgesics increasingly includes the novel research area of functional genomics, which combines data derived from various processes related to DNA sequence, gene expression or protein function and uses advanced methods of data mining and knowledge discovery with the goal of understanding the relationship between the genome and the phenotype. Its use in drug discovery and repurposing for analgesic indications has so far been performed using knowledge discovery in gene function and drug target-related databases; next-generation sequencing; and functional proteomics-based approaches. Here, we discuss recent efforts in functional genomics-based approaches to analgesic drug discovery and repurposing and highlight the potential of computational functional genomics in this field including a demonstration of the workflow using a novel R library 'dbtORA'.

Manufacturing engineering: Principles for optimization

NASA Astrophysics Data System (ADS)

Koenig, Daniel T.

Various subjects in the area of manufacturing engineering are addressed. The topics considered include: manufacturing engineering organization concepts and management techniques, factory capacity and loading techniques, capital equipment programs, machine tool and equipment selection and implementation, producibility engineering, methods, planning and work management, and process control engineering in job shops. Also discussed are: maintenance engineering, numerical control of machine tools, fundamentals of computer-aided design/computer-aided manufacture, computer-aided process planning and data collection, group technology basis for plant layout, environmental control and safety, and the Integrated Productivity Improvement Program.

The Impact of Students' Exploration Strategies on Discovery Learning Using Computer-Based Simulations

ERIC Educational Resources Information Center

Dalgarno, Barney; Kennedy, Gregor; Bennett, Sue

2014-01-01

Discovery-based learning designs incorporating active exploration are common within instructional software. However, researchers have highlighted empirical evidence showing that "pure" discovery learning is of limited value and strategies which reduce complexity and provide guidance to learners are important if potential learning…

Recent advances in automated protein design and its future challenges.

PubMed

Setiawan, Dani; Brender, Jeffrey; Zhang, Yang

2018-04-25

Protein function is determined by protein structure which is in turn determined by the corresponding protein sequence. If the rules that cause a protein to adopt a particular structure are understood, it should be possible to refine or even redefine the function of a protein by working backwards from the desired structure to the sequence. Automated protein design attempts to calculate the effects of mutations computationally with the goal of more radical or complex transformations than are accessible by experimental techniques. Areas covered: The authors give a brief overview of the recent methodological advances in computer-aided protein design, showing how methodological choices affect final design and how automated protein design can be used to address problems considered beyond traditional protein engineering, including the creation of novel protein scaffolds for drug development. Also, the authors address specifically the future challenges in the development of automated protein design. Expert opinion: Automated protein design holds potential as a protein engineering technique, particularly in cases where screening by combinatorial mutagenesis is problematic. Considering solubility and immunogenicity issues, automated protein design is initially more likely to make an impact as a research tool for exploring basic biology in drug discovery than in the design of protein biologics.

Analyzing Language in Suicide Notes and Legacy Tokens.

PubMed

Egnoto, Michael J; Griffin, Darrin J

2016-03-01

Identifying precursors that will aid in the discovery of individuals who may harm themselves or others has long been a focus of scholarly research. This work set out to determine if it is possible to use the legacy tokens of active shooters and notes left from individuals who completed suicide to uncover signals that foreshadow their behavior. A total of 25 suicide notes and 21 legacy tokens were compared with a sample of over 20,000 student writings for a preliminary computer-assisted text analysis to determine what differences can be coded with existing computer software to better identify students who may commit self-harm or harm to others. The results support that text analysis techniques with the Linguistic Inquiry and Word Count (LIWC) tool are effective for identifying suicidal or homicidal writings as distinct from each other and from a variety of student writings in an automated fashion. Findings indicate support for automated identification of writings that were associated with harm to self, harm to others, and various other student writing products. This work begins to uncover the viability or larger scale, low cost methods of automatic detection for individuals suffering from harmful ideation.

Grid-based Molecular Footprint Comparison Method for Docking and De Novo Design: Application to HIVgp41

PubMed Central

Mukherjee, Sudipto; Rizzo, Robert C.

2014-01-01

Scoring functions are a critically important component of computer-aided screening methods for the identification of lead compounds during early stages of drug discovery. Here, we present a new multi-grid implementation of the footprint similarity (FPS) scoring function that was recently developed in our laboratory which has proven useful for identification of compounds which bind to a protein on a per-residue basis in a way that resembles a known reference. The grid-based FPS method is much faster than its Cartesian-space counterpart which makes it computationally tractable for on-the-fly docking, virtual screening, or de novo design. In this work, we establish that: (i) relatively few grids can be used to accurately approximate Cartesian space footprint similarity, (ii) the method yields improved success over the standard DOCK energy function for pose identification across a large test set of experimental co-crystal structures, for crossdocking, and for database enrichment, and (iii) grid-based FPS scoring can be used to tailor construction of new molecules to have specific properties, as demonstrated in a series of test cases targeting the viral protein HIVgp41. The method will be made available in the program DOCK6. PMID:23436713

Quantum-Mechanics Methodologies in Drug Discovery: Applications of Docking and Scoring in Lead Optimization.

PubMed

Crespo, Alejandro; Rodriguez-Granillo, Agustina; Lim, Victoria T

2017-01-01

The development and application of quantum mechanics (QM) methodologies in computer- aided drug design have flourished in the last 10 years. Despite the natural advantage of QM methods to predict binding affinities with a higher level of theory than those methods based on molecular mechanics (MM), there are only a few examples where diverse sets of protein-ligand targets have been evaluated simultaneously. In this work, we review recent advances in QM docking and scoring for those cases in which a systematic analysis has been performed. In addition, we introduce and validate a simplified QM/MM expression to compute protein-ligand binding energies. Overall, QMbased scoring functions are generally better to predict ligand affinities than those based on classical mechanics. However, the agreement between experimental activities and calculated binding energies is highly dependent on the specific chemical series considered. The advantage of more accurate QM methods is evident in cases where charge transfer and polarization effects are important, for example when metals are involved in the binding process or when dispersion forces play a significant role as in the case of hydrophobic or stacking interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Accounting for receptor flexibility and enhanced sampling methods in computer-aided drug design.

PubMed

Sinko, William; Lindert, Steffen; McCammon, J Andrew

2013-01-01

Protein flexibility plays a major role in biomolecular recognition. In many cases, it is not obvious how molecular structure will change upon association with other molecules. In proteins, these changes can be major, with large deviations in overall backbone structure, or they can be more subtle as in a side-chain rotation. Either way the algorithms that predict the favorability of biomolecular association require relatively accurate predictions of the bound structure to give an accurate assessment of the energy involved in association. Here, we review a number of techniques that have been proposed to accommodate receptor flexibility in the simulation of small molecules binding to protein receptors. We investigate modifications to standard rigid receptor docking algorithms and also explore enhanced sampling techniques, and the combination of free energy calculations and enhanced sampling techniques. The understanding and allowance for receptor flexibility are helping to make computer simulations of ligand protein binding more accurate. These developments may help improve the efficiency of drug discovery and development. Efficiency will be essential as we begin to see personalized medicine tailored to individual patients, which means specific drugs are needed for each patient's genetic makeup. © 2012 John Wiley & Sons A/S.

Band Gap Engineering of Titania Systems Purposed for Photocatalytic Activity

NASA Astrophysics Data System (ADS)

Thurston, Cameron

Ab initio computer aided design drastically increases candidate population for highly specified material discovery and selection. These simulations, carried out through a first-principles computational approach, accurately extrapolate material properties and behavior. Titanium Dioxide (TiO2 ) is one such material that stands to gain a great deal from the use of these simulations. In its anatase form, titania (TiO2 ) has been found to exhibit a band gap nearing 3.2 eV. If titania is to become a viable alternative to other contemporary photoactive materials exhibiting band gaps better suited for the solar spectrum, then the band gap must be subsequently reduced. To lower the energy needed for electronic excitation, both transition metals and non-metals have been extensively researched and are currently viable candidates for the continued reduction of titania's band gap. The introduction of multicomponent atomic doping introduces new energy bands which tend to both reduce the band gap and recombination loss. Ta-N, Nb-N, V-N, Cr-N, Mo-N, and W-N substitutions were studied in titania and subsequent energy and band gap calculations show a favorable band gap reduction in the case of passivated systems.

Overview: early history of crop growth and photosynthesis modeling.

PubMed

El-Sharkawy, Mabrouk A

2011-02-01

As in industrial and engineering systems, there is a need to quantitatively study and analyze the many constituents of complex natural biological systems as well as agro-ecosystems via research-based mechanistic modeling. This objective is normally addressed by developing mathematically built descriptions of multilevel biological processes to provide biologists a means to integrate quantitatively experimental research findings that might lead to a better understanding of the whole systems and their interactions with surrounding environments. Aided with the power of computational capacities associated with computer technology then available, pioneering cropping systems simulations took place in the second half of the 20th century by several research groups across continents. This overview summarizes that initial pioneering effort made to simulate plant growth and photosynthesis of crop canopies, focusing on the discovery of gaps that exist in the current scientific knowledge. Examples are given for those gaps where experimental research was needed to improve the validity and application of the constructed models, so that their benefit to mankind was enhanced. Such research necessitates close collaboration among experimentalists and model builders while adopting a multidisciplinary/inter-institutional approach. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Translational Research 2.0: a framework for accelerating collaborative discovery.

PubMed

Asakiewicz, Chris

2014-05-01

The world wide web has revolutionized the conduct of global, cross-disciplinary research. In the life sciences, interdisciplinary approaches to problem solving and collaboration are becoming increasingly important in facilitating knowledge discovery and integration. Web 2.0 technologies promise to have a profound impact - enabling reproducibility, aiding in discovery, and accelerating and transforming medical and healthcare research across the healthcare ecosystem. However, knowledge integration and discovery require a consistent foundation upon which to operate. A foundation should be capable of addressing some of the critical issues associated with how research is conducted within the ecosystem today and how it should be conducted for the future. This article will discuss a framework for enhancing collaborative knowledge discovery across the medical and healthcare research ecosystem. A framework that could serve as a foundation upon which ecosystem stakeholders can enhance the way data, information and knowledge is created, shared and used to accelerate the translation of knowledge from one area of the ecosystem to another.

Prosthetically guided maxillofacial surgery: evaluation of the accuracy of a surgical guide and custom-made bone plate in oncology patients after mandibular reconstruction.

PubMed

Mazzoni, Simona; Marchetti, Claudio; Sgarzani, Rossella; Cipriani, Riccardo; Scotti, Roberto; Ciocca, Leonardo

2013-06-01

The aim of the present study was to evaluate the accuracy of prosthetically guided maxillofacial surgery in reconstructing the mandible with a free vascularized flap using custom-made bone plates and a surgical guide to cut the mandible and fibula. The surgical protocol was applied in a study group of seven consecutive mandibular-reconstructed patients who were compared with a control group treated using the standard preplating technique on stereolithographic models (indirect computer-aided design/computer-aided manufacturing method). The precision of both surgical techniques (prosthetically guided maxillofacial surgery and indirect computer-aided design/computer-aided manufacturing procedure) was evaluated by comparing preoperative and postoperative computed tomographic data and assessment of specific landmarks. With regard to midline deviation, no significant difference was documented between the test and control groups. With regard to mandibular angle shift, only one left angle shift on the lateral plane showed a statistically significant difference between the groups. With regard to angular deviation of the body axis, the data showed a significant difference in the arch deviation. All patients in the control group registered greater than 8 degrees of deviation, determining a facial contracture of the external profile at the lower margin of the mandible. With regard to condylar position, the postoperative condylar position was better in the test group than in the control group, although no significant difference was detected. The new protocol for mandibular reconstruction using computer-aided design/computer-aided manufacturing prosthetically guided maxillofacial surgery to construct custom-made guides and plates may represent a viable method of reproducing the patient's anatomical contour, giving the surgeon better procedural control and reducing procedure time. Therapeutic, III.

CCR Careers | Center for Cancer Research

Cancer.gov

Be part of our mission to make breakthrough scientific discoveries to find cures and treatments for cancer. Our principal investigators lead teams of laboratory scientists, trainees, clinicians, and administrators to unlock scientific knowledge to advance the fight against cancer and HIV/AIDS.

Teachers' Pets.

ERIC Educational Resources Information Center

Broderick, Patricia; Raymond, Allen

1994-01-01

Reviews nine teaching aids: (1) "Our World" (Troll); (2) "Comprehensive School Health Education" (Meeks Heit Publishing); (3) "America at School" (Pleasant Company); (4) "Tomie, Tomie, Tomie" (Val Hornburg); (5) "Frog Pondering" (Frog Publications); (6) "TalentEd" (Teacher Ideas Press); (7) "Scholastic Voyages of Discovery" (Scholastic); (8) "Nose…

Computer-Aided Reliability Estimation

NASA Technical Reports Server (NTRS)

Bavuso, S. J.; Stiffler, J. J.; Bryant, L. A.; Petersen, P. L.

1986-01-01

CARE III (Computer-Aided Reliability Estimation, Third Generation) helps estimate reliability of complex, redundant, fault-tolerant systems. Program specifically designed for evaluation of fault-tolerant avionics systems. However, CARE III general enough for use in evaluation of other systems as well.

Effectiveness of educational technology to improve patient care in pharmacy curricula.

PubMed

Smith, Michael A; Benedict, Neal

2015-02-17

A review of the literature on the effectiveness of educational technologies to teach patient care skills to pharmacy students was conducted. Nineteen articles met inclusion criteria for the review. Seven of the articles included computer-aided instruction, 4 utilized human-patient simulation, 1 used both computer-aided instruction and human-patient simulation, and 7 utilized virtual patients. Educational technology was employed with more than 2700 students at 12 colleges and schools of pharmacy in courses including pharmacotherapeutics, skills and patient care laboratories, drug diversion, and advanced pharmacy practice experience (APPE) orientation. Students who learned by means of human-patient simulation and virtual patients reported enjoying the learning activity, whereas the results with computer-aided instruction were mixed. Moreover, the effect on learning was significant in the human-patient simulation and virtual patient studies, while conflicting data emerged on the effectiveness of computer-aided instruction.

Assessment of Chair-side Computer-Aided Design and Computer-Aided Manufacturing Restorations: A Review of the Literature

PubMed Central

Baroudi, Kusai; Ibraheem, Shukran Nasser

2015-01-01

Background: This paper aimed to evaluate the application of computer-aided design and computer-aided manufacturing (CAD-CAM) technology and the factors that affect the survival of restorations. Materials and Methods: A thorough literature search using PubMed, Medline, Embase, Science Direct, Wiley Online Library and Grey literature were performed from the year 2004 up to June 2014. Only relevant research was considered. Results: The use of chair-side CAD/CAM systems is promising in all dental branches in terms of minimizing time and effort made by dentists, technicians and patients for restoring and maintaining patient oral function and aesthetic, while providing high quality outcome. Conclusion: The way of producing and placing the restorations made with the chair-side CAD/CAM (CEREC and E4D) devices is better than restorations made by conventional laboratory procedures. PMID:25954082

Computer-aided design/computer-aided manufacturing skull base drill.

PubMed

Couldwell, William T; MacDonald, Joel D; Thomas, Charles L; Hansen, Bradley C; Lapalikar, Aniruddha; Thakkar, Bharat; Balaji, Alagar K

2017-05-01

The authors have developed a simple device for computer-aided design/computer-aided manufacturing (CAD-CAM) that uses an image-guided system to define a cutting tool path that is shared with a surgical machining system for drilling bone. Information from 2D images (obtained via CT and MRI) is transmitted to a processor that produces a 3D image. The processor generates code defining an optimized cutting tool path, which is sent to a surgical machining system that can drill the desired portion of bone. This tool has applications for bone removal in both cranial and spine neurosurgical approaches. Such applications have the potential to reduce surgical time and associated complications such as infection or blood loss. The device enables rapid removal of bone within 1 mm of vital structures. The validity of such a machining tool is exemplified in the rapid (< 3 minutes machining time) and accurate removal of bone for transtemporal (for example, translabyrinthine) approaches.

The Research of Computer Aided Farm Machinery Designing Method Based on Ergonomics

NASA Astrophysics Data System (ADS)

Gao, Xiyin; Li, Xinling; Song, Qiang; Zheng, Ying

Along with agricultural economy development, the farm machinery product type Increases gradually, the ergonomics question is also getting more and more prominent. The widespread application of computer aided machinery design makes it possible that farm machinery design is intuitive, flexible and convenient. At present, because the developed computer aided ergonomics software has not suitable human body database, which is needed in view of farm machinery design in China, the farm machinery design have deviation in ergonomics analysis. This article puts forward that using the open database interface procedure in CATIA to establish human body database which aims at the farm machinery design, and reading the human body data to ergonomics module of CATIA can product practical application virtual body, using human posture analysis and human activity analysis module to analysis the ergonomics in farm machinery, thus computer aided farm machinery designing method based on engineering can be realized.

An esthetics rehabilitation with computer-aided design/ computer-aided manufacturing technology.

PubMed

Mazaro, Josá Vitor Quinelli; de Mello, Caroline Cantieri; Zavanelli, Adriana Cristina; Santiago, Joel Ferreira; Amoroso, Andressa Paschoal; Pellizzer, Eduardo Piza

2014-07-01

This paper describes a case of a rehabilitation involving Computer Aided Design/Computer Aided Manufacturing (CAD-CAM) system in implant supported and dental supported prostheses using zirconia as framework. The CAD-CAM technology has developed considerably over last few years, becoming a reality in dental practice. Among the widely used systems are the systems based on zirconia which demonstrate important physical and mechanical properties of high strength, adequate fracture toughness, biocompatibility and esthetics, and are indicated for unitary prosthetic restorations and posterior and anterior framework. All the modeling was performed by using CAD-CAM system and prostheses were cemented using resin cement best suited for each situation. The rehabilitation of the maxillary arch using zirconia framework demonstrated satisfactory esthetic and functional results after a 12-month control and revealed no biological and technical complications. This article shows the important of use technology CAD/CAM in the manufacture of dental prosthesis and implant-supported.

Computer-aided detection and quantification of endolymphatic hydrops within the mouse cochlea in vivo using optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, George S.; Kim, Jinkyung; Applegate, Brian E.; Oghalai, John S.

2017-07-01

Diseases that cause hearing loss and/or vertigo in humans such as Meniere's disease are often studied using animal models. The volume of endolymph within the inner ear varies with these diseases. Here, we used a mouse model of increased endolymph volume, endolymphatic hydrops, to develop a computer-aided objective approach to measure endolymph volume from images collected in vivo using optical coherence tomography. The displacement of Reissner's membrane from its normal position was measured in cochlear cross sections. We validated our computer-aided measurements with manual measurements and with trained observer labels. This approach allows for computer-aided detection of endolymphatic hydrops in mice, with test performance showing sensitivity of 91% and specificity of 87% using a running average of five measurements. These findings indicate that this approach is accurate and reliable for classifying endolymphatic hydrops and quantifying endolymph volume.

Modeling covalent-modifier drugs.

PubMed

Awoonor-Williams, Ernest; Walsh, Andrew G; Rowley, Christopher N

2017-11-01

In this review, we present a summary of how computer modeling has been used in the development of covalent-modifier drugs. Covalent-modifier drugs bind by forming a chemical bond with their target. This covalent binding can improve the selectivity of the drug for a target with complementary reactivity and result in increased binding affinities due to the strength of the covalent bond formed. In some cases, this results in irreversible inhibition of the target, but some targeted covalent inhibitor (TCI) drugs bind covalently but reversibly. Computer modeling is widely used in drug discovery, but different computational methods must be used to model covalent modifiers because of the chemical bonds formed. Structural and bioinformatic analysis has identified sites of modification that could yield selectivity for a chosen target. Docking methods, which are used to rank binding poses of large sets of inhibitors, have been augmented to support the formation of protein-ligand bonds and are now capable of predicting the binding pose of covalent modifiers accurately. The pK a 's of amino acids can be calculated in order to assess their reactivity towards electrophiles. QM/MM methods have been used to model the reaction mechanisms of covalent modification. The continued development of these tools will allow computation to aid in the development of new covalent-modifier drugs. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

The next scientific revolution.

PubMed

Hey, Tony

2010-11-01

For decades, computer scientists have tried to teach computers to think like human experts. Until recently, most of those efforts have failed to come close to generating the creative insights and solutions that seem to come naturally to the best researchers, doctors, and engineers. But now, Tony Hey, a VP of Microsoft Research, says we're witnessing the dawn of a new generation of powerful computer tools that can "mash up" vast quantities of data from many sources, analyze them, and help produce revolutionary scientific discoveries. Hey and his colleagues call this new method of scientific exploration "machine learning." At Microsoft, a team has already used it to innovate a method of predicting with impressive accuracy whether a patient with congestive heart failure who is released from the hospital will be readmitted within 30 days. It was developed by directing a computer program to pore through hundreds of thousands of data points on 300,000 patients and "learn" the profiles of patients most likely to be rehospitalized. The economic impact of this prediction tool could be huge: If a hospital understands the likelihood that a patient will "bounce back," it can design programs to keep him stable and save thousands of dollars in health care costs. Similar efforts to uncover important correlations that could lead to scientific breakthroughs are under way in oceanography, conservation, and AIDS research. And in business, deep data exploration has the potential to unearth critical insights about customers, supply chains, advertising effectiveness, and more.

Computer Aided Dosimetry and Verification of Exposure to Radiation

DTIC Science & Technology

2002-06-01

Event matrix 2. Hematopoietic * Absolute blood counts * Relative blood counts 3. Dosimetry * TLD * EPDQuantitative * Radiation survey * Whole body...EI1 Defence Research and Recherche et developpement Development Canada pour la d6fense Canada DEFENCE •mI•DEFENSE Computer Aided Dosimetry and...Aided Dosimetry and Verification of Exposure to Radiation Edward Waller SAIC Canada Robert Z Stodilka Radiation Effects Group, Space Systems and

Distributed Drug Discovery: Advancing Chemical Education through Contextualized Combinatorial Solid-Phase Organic Laboratories

ERIC Educational Resources Information Center

Scott, William L.; Denton, Ryan E.; Marrs, Kathleen A.; Durrant, Jacob D.; Samaritoni, J. Geno; Abraham, Milata M.; Brown, Stephen P.; Carnahan, Jon M.; Fischer, Lindsey G.; Glos, Courtney E.; Sempsrott, Peter J.; O'Donnell, Martin J.

2015-01-01

The Distributed Drug Discovery (D3) program trains students in three drug discovery disciplines (synthesis, computational analysis, and biological screening) while addressing the important challenge of discovering drug leads for neglected diseases. This article focuses on implementation of the synthesis component in the second-semester…

Scenario Educational Software: Design and Development of Discovery Learning.

ERIC Educational Resources Information Center

Keegan, Mark

This book shows how and why the computer is so well suited to producing discovery learning environments. An examination of the literature outlines four basic modes of instruction: didactic, Socratic, inquiry, and discovery. Research from the fields of education, psychology, and physiology is presented to demonstrate the many strengths of…

A Metric for Reducing False Positives in the Computer-Aided Detection of Breast Cancer from Dynamic Contrast-Enhanced Magnetic Resonance Imaging Based Screening Examinations of High-Risk Women.

PubMed

Levman, Jacob E D; Gallego-Ortiz, Cristina; Warner, Ellen; Causer, Petrina; Martel, Anne L

2016-02-01

Magnetic resonance imaging (MRI)-enabled cancer screening has been shown to be a highly sensitive method for the early detection of breast cancer. Computer-aided detection systems have the potential to improve the screening process by standardizing radiologists to a high level of diagnostic accuracy. This retrospective study was approved by the institutional review board of Sunnybrook Health Sciences Centre. This study compares the performance of a proposed method for computer-aided detection (based on the second-order spatial derivative of the relative signal intensity) with the signal enhancement ratio (SER) on MRI-based breast screening examinations. Comparison is performed using receiver operating characteristic (ROC) curve analysis as well as free-response receiver operating characteristic (FROC) curve analysis. A modified computer-aided detection system combining the proposed approach with the SER method is also presented. The proposed method provides improvements in the rates of false positive markings over the SER method in the detection of breast cancer (as assessed by FROC analysis). The modified computer-aided detection system that incorporates both the proposed method and the SER method yields ROC results equal to that produced by SER while simultaneously providing improvements over the SER method in terms of false positives per noncancerous exam. The proposed method for identifying malignancies outperforms the SER method in terms of false positives on a challenging dataset containing many small lesions and may play a useful role in breast cancer screening by MRI as part of a computer-aided detection system.

Computer Aided Drafting Packages for Secondary Education. Edition 2. PC DOS Compatible Programs. A MicroSIFT Quarterly Report.

ERIC Educational Resources Information Center

Pollard, Jim

This report reviews eight IBM-compatible software packages that are available to secondary schools to teach computer-aided drafting (CAD). Software packages to be considered were selected following reviews of CAD periodicals, computers in education periodicals, advertisements, and recommendations of teachers. The packages were then rated by…

Siren Songs and a Skeptic.

ERIC Educational Resources Information Center

O'Brien, George M.

This paper reports on an on-going experiment in computer-aided language instruction. In 1972, a class of beginning German students at the Duluth campus of the University of Minnesota volunteered to test two pedagogic theories: (1) Could a computer-aided course be used by a class and an instructor who knew nothing of computers and who had to rely…

PEO Integration Acronym Book

DTIC Science & Technology

2011-02-01

Command CASE Computer Aided Software Engineering CASEVAC Casualty Evacuation CASTFOREM Combined Arms And Support Task Force Evaluation Model CAT Center For...Advanced Technologies CAT Civil Affairs Team CAT Combined Arms Training CAT Crew Integration CAT Crisis Action Team CATIA Computer-Aided Three...Dimensional Interactive Application CATOX Catalytic Oxidation CATS Combined Arms Training Strategy CATT Combined Arms Tactical Trainer CATT Computer

XVis: Visualization for the Extreme-Scale Scientific-Computation Ecosystem: Mid-year report FY17 Q2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreland, Kenneth D.; Pugmire, David; Rogers, David

The XVis project brings together the key elements of research to enable scientific discovery at extreme scale. Scientific computing will no longer be purely about how fast computations can be performed. Energy constraints, processor changes, and I/O limitations necessitate significant changes in both the software applications used in scientific computation and the ways in which scientists use them. Components for modeling, simulation, analysis, and visualization must work together in a computational ecosystem, rather than working independently as they have in the past. This project provides the necessary research and infrastructure for scientific discovery in this new computational ecosystem by addressingmore » four interlocking challenges: emerging processor technology, in situ integration, usability, and proxy analysis.« less

XVis: Visualization for the Extreme-Scale Scientific-Computation Ecosystem: Year-end report FY17.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreland, Kenneth D.; Pugmire, David; Rogers, David

The XVis project brings together the key elements of research to enable scientific discovery at extreme scale. Scientific computing will no longer be purely about how fast computations can be performed. Energy constraints, processor changes, and I/O limitations necessitate significant changes in both the software applications used in scientific computation and the ways in which scientists use them. Components for modeling, simulation, analysis, and visualization must work together in a computational ecosystem, rather than working independently as they have in the past. This project provides the necessary research and infrastructure for scientific discovery in this new computational ecosystem by addressingmore » four interlocking challenges: emerging processor technology, in situ integration, usability, and proxy analysis.« less

XVis: Visualization for the Extreme-Scale Scientific-Computation Ecosystem. Mid-year report FY16 Q2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreland, Kenneth D.; Sewell, Christopher; Childs, Hank

The XVis project brings together the key elements of research to enable scientific discovery at extreme scale. Scientific computing will no longer be purely about how fast computations can be performed. Energy constraints, processor changes, and I/O limitations necessitate significant changes in both the software applications used in scientific computation and the ways in which scientists use them. Components for modeling, simulation, analysis, and visualization must work together in a computational ecosystem, rather than working independently as they have in the past. This project provides the necessary research and infrastructure for scientific discovery in this new computational ecosystem by addressingmore » four interlocking challenges: emerging processor technology, in situ integration, usability, and proxy analysis.« less

XVis: Visualization for the Extreme-Scale Scientific-Computation Ecosystem: Year-end report FY15 Q4.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreland, Kenneth D.; Sewell, Christopher; Childs, Hank

The XVis project brings together the key elements of research to enable scientific discovery at extreme scale. Scientific computing will no longer be purely about how fast computations can be performed. Energy constraints, processor changes, and I/O limitations necessitate significant changes in both the software applications used in scientific computation and the ways in which scientists use them. Components for modeling, simulation, analysis, and visualization must work together in a computational ecosystem, rather than working independently as they have in the past. This project provides the necessary research and infrastructure for scientific discovery in this new computational ecosystem by addressingmore » four interlocking challenges: emerging processor technology, in situ integration, usability, and proxy analysis.« less

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

PubMed

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug discovery and play an important role in optimizing multi-target drug discovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Miscellaneous Topics in Computer-Aided Drug Design: Synthetic Accessibility and GPU Computing, and Other Topics.

PubMed

Fukunishi, Yoshifumi; Mashimo, Tadaaki; Misoo, Kiyotaka; Wakabayashi, Yoshinori; Miyaki, Toshiaki; Ohta, Seiji; Nakamura, Mayu; Ikeda, Kazuyoshi

2016-01-01

Computer-aided drug design is still a state-of-the-art process in medicinal chemistry, and the main topics in this field have been extensively studied and well reviewed. These topics include compound databases, ligand-binding pocket prediction, protein-compound docking, virtual screening, target/off-target prediction, physical property prediction, molecular simulation and pharmacokinetics/pharmacodynamics (PK/PD) prediction. Message and Conclusion: However, there are also a number of secondary or miscellaneous topics that have been less well covered. For example, methods for synthesizing and predicting the synthetic accessibility (SA) of designed compounds are important in practical drug development, and hardware/software resources for performing the computations in computer-aided drug design are crucial. Cloud computing and general purpose graphics processing unit (GPGPU) computing have been used in virtual screening and molecular dynamics simulations. Not surprisingly, there is a growing demand for computer systems which combine these resources. In the present review, we summarize and discuss these various topics of drug design.

Miscellaneous Topics in Computer-Aided Drug Design: Synthetic Accessibility and GPU Computing, and Other Topics

PubMed Central

Fukunishi, Yoshifumi; Mashimo, Tadaaki; Misoo, Kiyotaka; Wakabayashi, Yoshinori; Miyaki, Toshiaki; Ohta, Seiji; Nakamura, Mayu; Ikeda, Kazuyoshi

2016-01-01

Abstract: Background Computer-aided drug design is still a state-of-the-art process in medicinal chemistry, and the main topics in this field have been extensively studied and well reviewed. These topics include compound databases, ligand-binding pocket prediction, protein-compound docking, virtual screening, target/off-target prediction, physical property prediction, molecular simulation and pharmacokinetics/pharmacodynamics (PK/PD) prediction. Message and Conclusion: However, there are also a number of secondary or miscellaneous topics that have been less well covered. For example, methods for synthesizing and predicting the synthetic accessibility (SA) of designed compounds are important in practical drug development, and hardware/software resources for performing the computations in computer-aided drug design are crucial. Cloud computing and general purpose graphics processing unit (GPGPU) computing have been used in virtual screening and molecular dynamics simulations. Not surprisingly, there is a growing demand for computer systems which combine these resources. In the present review, we summarize and discuss these various topics of drug design. PMID:27075578

Semi-automated surface mapping via unsupervised classification

NASA Astrophysics Data System (ADS)

D'Amore, M.; Le Scaon, R.; Helbert, J.; Maturilli, A.

2017-09-01

Due to the increasing volume of the returned data from space mission, the human search for correlation and identification of interesting features becomes more and more unfeasible. Statistical extraction of features via machine learning methods will increase the scientific output of remote sensing missions and aid the discovery of yet unknown feature hidden in dataset. Those methods exploit algorithm trained on features from multiple instrument, returning classification maps that explore intra-dataset correlation, allowing for the discovery of unknown features. We present two applications, one for Mercury and one for Vesta.

False Discovery Control in Large-Scale Spatial Multiple Testing

PubMed Central

Sun, Wenguang; Reich, Brian J.; Cai, T. Tony; Guindani, Michele; Schwartzman, Armin

2014-01-01

Summary This article develops a unified theoretical and computational framework for false discovery control in multiple testing of spatial signals. We consider both point-wise and cluster-wise spatial analyses, and derive oracle procedures which optimally control the false discovery rate, false discovery exceedance and false cluster rate, respectively. A data-driven finite approximation strategy is developed to mimic the oracle procedures on a continuous spatial domain. Our multiple testing procedures are asymptotically valid and can be effectively implemented using Bayesian computational algorithms for analysis of large spatial data sets. Numerical results show that the proposed procedures lead to more accurate error control and better power performance than conventional methods. We demonstrate our methods for analyzing the time trends in tropospheric ozone in eastern US. PMID:25642138

Using Innovative Tools to Teach Computer Application to Business Students--A Hawthorne Effect or Successful Implementation Here to Stay

ERIC Educational Resources Information Center

Khan, Zeenath Reza

2014-01-01

A year after the primary study that tested the impact of introducing blended learning and guided discovery to help teach computer application to business students, this paper looks into the continued success of using guided discovery and blended learning with learning management system in and out of classrooms to enhance student learning.…

Shaded-Color Picture Generation of Computer-Defined Arbitrary Shapes

NASA Technical Reports Server (NTRS)

Cozzolongo, J. V.; Hermstad, D. L.; Mccoy, D. S.; Clark, J.

1986-01-01

SHADE computer program generates realistic color-shaded pictures from computer-defined arbitrary shapes. Objects defined for computer representation displayed as smooth, color-shaded surfaces, including varying degrees of transparency. Results also used for presentation of computational results. By performing color mapping, SHADE colors model surface to display analysis results as pressures, stresses, and temperatures. NASA has used SHADE extensively in sign and analysis of high-performance aircraft. Industry should find applications for SHADE in computer-aided design and computer-aided manufacturing. SHADE written in VAX FORTRAN and MACRO Assembler for either interactive or batch execution.

Computer-aided dispatch--traffic management center field operational test final detailed test plan : WSDOT deployment

DOT National Transportation Integrated Search

2003-10-01

The purpose of this document is to expand upon the evaluation components presented in "Computer-aided dispatch--traffic management center field operational test final evaluation plan : WSDOT deployment". This document defines the objective, approach,...

Computer-aided dispatch--traffic management center field operational test : Washington State final report

DOT National Transportation Integrated Search

2006-05-01

This document provides the final report for the evaluation of the USDOT-sponsored Computer-Aided Dispatch - Traffic Management Center Integration Field Operations Test in the State of Washington. The document discusses evaluation findings in the foll...

Denver RTD's computer aided dispatch/automatic vehicle location system : the human factors consequences

DOT National Transportation Integrated Search

1999-09-01

This report documents what happened to employees' work procedures when their employer when their employer installed Computer Aided Disptach/Automatic Vehicle Locator (CAD/AVL) technology to provide real-time surveillance of vehicles and to upgrade ra...

The University of Michigan's Computer-Aided Engineering Network.

ERIC Educational Resources Information Center

Atkins, D. E.; Olsen, Leslie A.

1986-01-01

Presents an overview of the Computer-Aided Engineering Network (CAEN) of the University of Michigan. Describes its arrangement of workstations, communication networks, and servers. Outlines the factors considered in hardware and software decision making. Reviews the program's impact on students. (ML)

Computer-aided engineering of semiconductor integrated circuits

NASA Astrophysics Data System (ADS)

Meindl, J. D.; Dutton, R. W.; Gibbons, J. F.; Helms, C. R.; Plummer, J. D.; Tiller, W. A.; Ho, C. P.; Saraswat, K. C.; Deal, B. E.; Kamins, T. I.

1980-07-01

Economical procurement of small quantities of high performance custom integrated circuits for military systems is impeded by inadequate process, device and circuit models that handicap low cost computer aided design. The principal objective of this program is to formulate physical models of fabrication processes, devices and circuits to allow total computer-aided design of custom large-scale integrated circuits. The basic areas under investigation are (1) thermal oxidation, (2) ion implantation and diffusion, (3) chemical vapor deposition of silicon and refractory metal silicides, (4) device simulation and analytic measurements. This report discusses the fourth year of the program.

CAD system for footwear design based on whole real 3D data of last surface

NASA Astrophysics Data System (ADS)

Song, Wanzhong; Su, Xianyu

2000-10-01

Two major parts of application of CAD in footwear design are studied: the development of last surface; computer-aided design of planar shoe-template. A new quasi-experiential development algorithm of last surface based on triangulation approximation is presented. This development algorithm consumes less time and does not need any interactive operation for precisely development compared with other development algorithm of last surface. Based on this algorithm, a software, SHOEMAKERTM, which contains computer aided automatic measurement, automatic development of last surface and computer aide design of shoe-template has been developed.

Training Aids for Online Instruction: An Analysis.

ERIC Educational Resources Information Center

Guy, Robin Frederick

This paper describes a number of different types of training aids currently employed in online training: non-interactive audiovisual presentations; interactive computer-based aids; partially interactive aids based on recorded searches; print-based materials; and kits. The advantages and disadvantages of each type of aid are noted, and a table…

Financial Aid for Full-Time Undergraduates. Higher Education Panel Report Number 60.

ERIC Educational Resources Information Center

Andersen, Charles J.

The level and composition of student financial aid for undergraduate students were estimated, with attention to estimated number of aid recipients, the total amount they received, the distribution of aided students by their families' income level, the composition of their aid packages, and the use of computers in the administration of aid. In…

Terminology for Neuroscience Data Discovery: Multi-tree Syntax and Investigator-Derived Semantics

PubMed Central

Goldberg, David H.; Grafstein, Bernice; Robert, Adrian; Gardner, Esther P.

2009-01-01

The Neuroscience Information Framework (NIF), developed for the NIH Blueprint for Neuroscience Research and available at http://nif.nih.gov and http://neurogateway.org, is built upon a set of coordinated terminology components enabling data and web-resource description and selection. Core NIF terminologies use a straightforward syntax designed for ease of use and for navigation by familiar web interfaces, and readily exportable to aid development of relational-model databases for neuroscience data sharing. Datasets, data analysis tools, web resources, and other entities are characterized by multiple descriptors, each addressing core concepts, including data type, acquisition technique, neuroanatomy, and cell class. Terms for each concept are organized in a tree structure, providing is-a and has-a relations. Broad general terms near each root span the category or concept and spawn more detailed entries for specificity. Related but distinct concepts (e.g., brain area and depth) are specified by separate trees, for easier navigation than would be required by graph representation. Semantics enabling NIF data discovery were selected at one or more workshops by investigators expert in particular systems (vision, olfaction, behavioral neuroscience, neurodevelopment), brain areas (cerebellum, thalamus, hippocampus), preparations (molluscs, fly), diseases (neurodegenerative disease), or techniques (microscopy, computation and modeling, neurogenetics). Workshop-derived integrated term lists are available Open Source at http://brainml.org; a complete list of participants is at http://brainml.org/workshops. PMID:18958630

Computationally guided discovery of thermoelectric materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorai, Prashun; Stevanović, Vladan; Toberer, Eric S.

The potential for advances in thermoelectric materials, and thus solid-state refrigeration and power generation, is immense. Progress so far has been limited by both the breadth and diversity of the chemical space and the serial nature of experimental work. In this Review, we discuss how recent computational advances are revolutionizing our ability to predict electron and phonon transport and scattering, as well as materials dopability, and we examine efficient approaches to calculating critical transport properties across large chemical spaces. When coupled with experimental feedback, these high-throughput approaches can stimulate the discovery of new classes of thermoelectric materials. Within smaller materialsmore » subsets, computations can guide the optimal chemical and structural tailoring to enhance materials performance and provide insight into the underlying transport physics. Beyond perfect materials, computations can be used for the rational design of structural and chemical modifications (such as defects, interfaces, dopants and alloys) to provide additional control on transport properties to optimize performance. Through computational predictions for both materials searches and design, a new paradigm in thermoelectric materials discovery is emerging.« less

Computational Discovery of Materials Using the Firefly Algorithm

NASA Astrophysics Data System (ADS)

Avendaño-Franco, Guillermo; Romero, Aldo

Our current ability to model physical phenomena accurately, the increase computational power and better algorithms are the driving forces behind the computational discovery and design of novel materials, allowing for virtual characterization before their realization in the laboratory. We present the implementation of a novel firefly algorithm, a population-based algorithm for global optimization for searching the structure/composition space. This novel computation-intensive approach naturally take advantage of concurrency, targeted exploration and still keeping enough diversity. We apply the new method in both periodic and non-periodic structures and we present the implementation challenges and solutions to improve efficiency. The implementation makes use of computational materials databases and network analysis to optimize the search and get insights about the geometric structure of local minima on the energy landscape. The method has been implemented in our software PyChemia, an open-source package for materials discovery. We acknowledge the support of DMREF-NSF 1434897 and the Donors of the American Chemical Society Petroleum Research Fund for partial support of this research under Contract 54075-ND10.

Computationally guided discovery of thermoelectric materials

DOE PAGES

Gorai, Prashun; Stevanović, Vladan; Toberer, Eric S.

2017-08-22

The potential for advances in thermoelectric materials, and thus solid-state refrigeration and power generation, is immense. Progress so far has been limited by both the breadth and diversity of the chemical space and the serial nature of experimental work. In this Review, we discuss how recent computational advances are revolutionizing our ability to predict electron and phonon transport and scattering, as well as materials dopability, and we examine efficient approaches to calculating critical transport properties across large chemical spaces. When coupled with experimental feedback, these high-throughput approaches can stimulate the discovery of new classes of thermoelectric materials. Within smaller materialsmore » subsets, computations can guide the optimal chemical and structural tailoring to enhance materials performance and provide insight into the underlying transport physics. Beyond perfect materials, computations can be used for the rational design of structural and chemical modifications (such as defects, interfaces, dopants and alloys) to provide additional control on transport properties to optimize performance. Through computational predictions for both materials searches and design, a new paradigm in thermoelectric materials discovery is emerging.« less

Usability Studies in Virtual and Traditional Computer Aided Design Environments for Fault Identification

DTIC Science & Technology

2017-08-08

Usability Studies In Virtual And Traditional Computer Aided Design Environments For Fault Identification Dr. Syed Adeel Ahmed, Xavier University...virtual environment with wand interfaces compared directly with a workstation non-stereoscopic traditional CAD interface with keyboard and mouse. In...the differences in interaction when compared with traditional human computer interfaces. This paper provides analysis via usability study methods

A State-of-the-Art Review of the Real-Time Computer-Aided Study of the Writing Process

ERIC Educational Resources Information Center

Abdel Latif, Muhammad M.

2008-01-01

Writing researchers have developed various methods for investigating the writing process since the 1970s. The early 1980s saw the occurrence of the real-time computer-aided study of the writing process that relies on the protocols generated by recording the computer screen activities as writers compose using the word processor. This article…

Computer-Aided Transcription in the Courts. Executive Summary. National Center Publication No. R-0058.

ERIC Educational Resources Information Center

National Center for State Courts, Williamsburg, VA.

This report summarizes the findings of the Computer-Aided Transcription (CAT) Project, which conducted a 14-month study of the technology and use of computer systems for translating into English the shorthand notes taken by court reporters on stenotype machines. Included are the state of the art of CAT at the end of 1980 and anticipated future…

Wusor II: A Computer Aided Instruction Program with Student Modelling Capabilities. AI Memo 417.

ERIC Educational Resources Information Center

Carr, Brian

Wusor II is the second intelligent computer aided instruction (ICAI) program that has been developed to monitor the progress of, and offer suggestions to, students playing Wumpus, a computer game designed to teach logical thinking and problem solving. From the earlier efforts with Wusor I, it was possible to produce a rule-based expert which…

Pulsar discovery by global volunteer computing.

PubMed

Knispel, B; Allen, B; Cordes, J M; Deneva, J S; Anderson, D; Aulbert, C; Bhat, N D R; Bock, O; Bogdanov, S; Brazier, A; Camilo, F; Champion, D J; Chatterjee, S; Crawford, F; Demorest, P B; Fehrmann, H; Freire, P C C; Gonzalez, M E; Hammer, D; Hessels, J W T; Jenet, F A; Kasian, L; Kaspi, V M; Kramer, M; Lazarus, P; van Leeuwen, J; Lorimer, D R; Lyne, A G; Machenschalk, B; McLaughlin, M A; Messenger, C; Nice, D J; Papa, M A; Pletsch, H J; Prix, R; Ransom, S M; Siemens, X; Stairs, I H; Stappers, B W; Stovall, K; Venkataraman, A

2010-09-10

Einstein@Home aggregates the computer power of hundreds of thousands of volunteers from 192 countries to mine large data sets. It has now found a 40.8-hertz isolated pulsar in radio survey data from the Arecibo Observatory taken in February 2007. Additional timing observations indicate that this pulsar is likely a disrupted recycled pulsar. PSR J2007+2722's pulse profile is remarkably wide with emission over almost the entire spin period; the pulsar likely has closely aligned magnetic and spin axes. The massive computing power provided by volunteers should enable many more such discoveries.

Computational System For Rapid CFD Analysis In Engineering

NASA Technical Reports Server (NTRS)

Barson, Steven L.; Ascoli, Edward P.; Decroix, Michelle E.; Sindir, Munir M.

1995-01-01

Computational system comprising modular hardware and software sub-systems developed to accelerate and facilitate use of techniques of computational fluid dynamics (CFD) in engineering environment. Addresses integration of all aspects of CFD analysis process, including definition of hardware surfaces, generation of computational grids, CFD flow solution, and postprocessing. Incorporates interfaces for integration of all hardware and software tools needed to perform complete CFD analysis. Includes tools for efficient definition of flow geometry, generation of computational grids, computation of flows on grids, and postprocessing of flow data. System accepts geometric input from any of three basic sources: computer-aided design (CAD), computer-aided engineering (CAE), or definition by user.

Unit cell-based computer-aided manufacturing system for tissue engineering.

PubMed

Kang, Hyun-Wook; Park, Jeong Hun; Kang, Tae-Yun; Seol, Young-Joon; Cho, Dong-Woo

2012-03-01

Scaffolds play an important role in the regeneration of artificial tissues or organs. A scaffold is a porous structure with a micro-scale inner architecture in the range of several to several hundreds of micrometers. Therefore, computer-aided construction of scaffolds should provide sophisticated functionality for porous structure design and a tool path generation strategy that can achieve micro-scale architecture. In this study, a new unit cell-based computer-aided manufacturing (CAM) system was developed for the automated design and fabrication of a porous structure with micro-scale inner architecture that can be applied to composite tissue regeneration. The CAM system was developed by first defining a data structure for the computing process of a unit cell representing a single pore structure. Next, an algorithm and software were developed and applied to construct porous structures with a single or multiple pore design using solid freeform fabrication technology and a 3D tooth/spine computer-aided design model. We showed that this system is quite feasible for the design and fabrication of a scaffold for tissue engineering.

Computer-aided dispatch--traffic management center field operational test : state of Utah final report

DOT National Transportation Integrated Search

2006-07-01

This document provides the final report for the evaluation of the USDOT-sponsored Computer-Aided Dispatch Traffic Management Center Integration Field Operations Test in the State of Utah. The document discusses evaluation findings in the followin...

USE OF COMPUTER-AIDED PROCESS ENGINEERING TOOL IN POLLUTION PREVENTION

EPA Science Inventory

Computer-Aided Process Engineering has become established in industry as a design tool. With the establishment of the CAPE-OPEN software specifications for process simulation environments. CAPE-OPEN provides a set of "middleware" standards that enable software developers to acces...

Using CAD Programs in CAL.

ERIC Educational Resources Information Center

Boardman, D.

1979-01-01

Practical experience has shown that computer aided design programs can provide an invaluable aid in the learning process when integrated into the syllabus in lecture and laboratory periods. This should be a major area of future development of computer assisted learning in engineering education. (Author/CMV)

Computer-aided dispatch--traffic management center field operational test final test plans : state of Utah

DOT National Transportation Integrated Search

2004-01-01

The purpose of this document is to expand upon the evaluation components presented in "Computer-aided dispatch--traffic management center field operational test final evaluation plan : state of Utah". This document defines the objective, approach, an...

Computer-Aided Geometry Modeling

NASA Technical Reports Server (NTRS)

Shoosmith, J. N. (Compiler); Fulton, R. E. (Compiler)

1984-01-01

Techniques in computer-aided geometry modeling and their application are addressed. Mathematical modeling, solid geometry models, management of geometric data, development of geometry standards, and interactive and graphic procedures are discussed. The applications include aeronautical and aerospace structures design, fluid flow modeling, and gas turbine design.

APPLICATION OF COMPUTER AIDED TOMOGRAPHY (CAT) TO THE STUDY OF MARINE BENTIC COMMUNITIES

EPA Science Inventory

Sediment cores were imaged using a Computer-Aided Tomography (CT) scanner at Massachusetts General Hospital, Boston, Massachusetts, United States. Procedures were developed, using the attenuation of X-rays, to differentiate between sediment and the water contained in macrobenthic...

Materials discovery guided by data-driven insights

NASA Astrophysics Data System (ADS)

Klintenberg, Mattias

As the computational power continues to grow systematic computational exploration has become an important tool for materials discovery. In this presentation the Electronic Structure Project (ESP/ELSA) will be discussed and a number of examples presented that show some of the capabilities of a data-driven methodology for guiding materials discovery. These examples include topological insulators, detector materials and 2D materials. ESP/ELSA is an initiative that dates back to 2001 and today contain many tens of thousands of materials that have been investigated using a robust and high accuracy electronic structure method (all-electron FP-LMTO) thus providing basic materials first-principles data for most inorganic compounds that have been structurally characterized. The web-site containing the ESP/ELSA data has as of today been accessed from more than 4,000 unique computers from all around the world.

Orthogonal Chip Based Electronic Sensors for Chemical Agents

DTIC Science & Technology

2012-04-06

operation with ultralow power requirements. This work has been carried out with the aid of substrate wafers provided by Qualcomm . The initial...produced by Qualcomm as a less expensive OTFT platform for sensors. 8. New Discoveries Air-stable organic thin-film transistor (OTFT) sensors

Locate, Plan, Develop, Use An Outdoor Classroom.

ERIC Educational Resources Information Center

Soil Conservation Service (USDA), Upper Darby, PA.

Designed to aid educational institutions and community organizations in selecting, planning, developing and using outdoor learning areas as outdoor classrooms, this guide includes: (1) Learning by Discovery (scientific, cultural, and recreational goals); (2) The Initial Planning Effort (use of: a planning committee including teachers,…

Use of model organism and disease databases to support matchmaking for human disease gene discovery.

PubMed

Mungall, Christopher J; Washington, Nicole L; Nguyen-Xuan, Jeremy; Condit, Christopher; Smedley, Damian; Köhler, Sebastian; Groza, Tudor; Shefchek, Kent; Hochheiser, Harry; Robinson, Peter N; Lewis, Suzanna E; Haendel, Melissa A

2015-10-01

The Matchmaker Exchange application programming interface (API) allows searching a patient's genotypic or phenotypic profiles across clinical sites, for the purposes of cohort discovery and variant disease causal validation. This API can be used not only to search for matching patients, but also to match against public disease and model organism data. This public disease data enable matching known diseases and variant-phenotype associations using phenotype semantic similarity algorithms developed by the Monarch Initiative. The model data can provide additional evidence to aid diagnosis, suggest relevant models for disease mechanism and treatment exploration, and identify collaborators across the translational divide. The Monarch Initiative provides an implementation of this API for searching multiple integrated sources of data that contextualize the knowledge about any given patient or patient family into the greater biomedical knowledge landscape. While this corpus of data can aid diagnosis, it is also the beginning of research to improve understanding of rare human diseases. © 2015 WILEY PERIODICALS, INC.

Strategies for identifying new prions in yeast

PubMed Central

MacLea, Kyle S

2011-01-01

The unexpected discovery of two prions, [URE3] and [PSI+], in Saccharomyces cerevisiae led to questions about how many other proteins could undergo similar prion-based structural conversions. However, [URE3] and [PSI+] were discovered by serendipity in genetic screens. Cataloging the full range of prions in yeast or in other organisms will therefore require more systematic search methods. Taking advantage of some of the unique features of prions, various researchers have developed bioinformatic and experimental methods for identifying novel prion proteins. These methods have generated long lists of prion candidates. The systematic testing of some of these prion candidates has led to notable successes; however, even in yeast, where rapid growth rate and ease of genetic manipulation aid in testing for prion activity, such candidate testing is laborious. Development of better methods to winnow the field of prion candidates will greatly aid in the discovery of new prions, both in yeast and in other organisms, and help us to better understand the role of prions in biology. PMID:22052351

Early nucleoside reverse transcriptase inhibitors for the treatment of HIV: a brief history of stavudine (D4T) and its comparison with other dideoxynucleosides.

PubMed

Martin, John C; Hitchcock, Michael J M; De Clercq, Erik; Prusoff, William H

2010-01-01

The occasion of this 25th anniversary issue encouraged us to reminisce about the important history of the discovery of the dideoxynucleoside analogues for the treatment of HIV/AIDS and to chronicle our thoughts about a particular exciting and rewarding period of our scientific careers. Following the identification of the anti-HIV activity of zidovudine (AZT), we participated in the urgent quest to discover optimal treatments of HIV infection and AIDS. A number of previously synthesized nucleoside analogues were comparatively evaluated, and stavudine (D4T) emerged as a promising candidate for development. Following clinical evaluation, D4T became a mainstay of the initial antiretroviral combination therapy, prolonging and saving numerous lives. It has only recently been supplanted by better-tolerated treatments. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010. Copyright 2009 Elsevier B.V. All rights reserved.

A tutorial on the use of ROC analysis for computer-aided diagnostic systems.

PubMed

Scheipers, Ulrich; Perrey, Christian; Siebers, Stefan; Hansen, Christian; Ermert, Helmut

2005-07-01

The application of the receiver operating characteristic (ROC) curve for computer-aided diagnostic systems is reviewed. A statistical framework is presented and different methods of evaluating the classification performance of computer-aided diagnostic systems, and, in particular, systems for ultrasonic tissue characterization, are derived. Most classifiers that are used today are dependent on a separation threshold, which can be chosen freely in many cases. The separation threshold separates the range of output values of the classification system into different target groups, thus conducting the actual classification process. In the first part of this paper, threshold specific performance measures, e.g., sensitivity and specificity, are presented. In the second part, a threshold-independent performance measure, the area under the ROC curve, is reviewed. Only the use of separation threshold-independent performance measures provides classification results that are overall representative for computer-aided diagnostic systems. The following text was motivated by the lack of a complete and definite discussion of the underlying subject in available textbooks, references and publications. Most manuscripts published so far address the theme of performance evaluation using ROC analysis in a manner too general to be practical for everyday use in the development of computer-aided diagnostic systems. Nowadays, the user of computer-aided diagnostic systems typically handles huge amounts of numerical data, not always distributed normally. Many assumptions made in more or less theoretical works on ROC analysis are no longer valid for real-life data. The paper aims at closing the gap between theoretical works and real-life data. The review provides the interested scientist with information needed to conduct ROC analysis and to integrate algorithms performing ROC analysis into classification systems while understanding the basic principles of classification.

The importance of employing computational resources for the automation of drug discovery.

PubMed

Rosales-Hernández, Martha Cecilia; Correa-Basurto, José

2015-03-01

The application of computational tools to drug discovery helps researchers to design and evaluate new drugs swiftly with a reduce economic resources. To discover new potential drugs, computational chemistry incorporates automatization for obtaining biological data such as adsorption, distribution, metabolism, excretion and toxicity (ADMET), as well as drug mechanisms of action. This editorial looks at examples of these computational tools, including docking, molecular dynamics simulation, virtual screening, quantum chemistry, quantitative structural activity relationship, principal component analysis and drug screening workflow systems. The authors then provide their perspectives on the importance of these techniques for drug discovery. Computational tools help researchers to design and discover new drugs for the treatment of several human diseases without side effects, thus allowing for the evaluation of millions of compounds with a reduced cost in both time and economic resources. The problem is that operating each program is difficult; one is required to use several programs and understand each of the properties being tested. In the future, it is possible that a single computer and software program will be capable of evaluating the complete properties (mechanisms of action and ADMET properties) of ligands. It is also possible that after submitting one target, this computer-software will be capable of suggesting potential compounds along with ways to synthesize them, and presenting biological models for testing.

Using the iPlant collaborative discovery environment.

PubMed

Oliver, Shannon L; Lenards, Andrew J; Barthelson, Roger A; Merchant, Nirav; McKay, Sheldon J

2013-06-01

The iPlant Collaborative is an academic consortium whose mission is to develop an informatics and social infrastructure to address the "grand challenges" in plant biology. Its cyberinfrastructure supports the computational needs of the research community and facilitates solving major challenges in plant science. The Discovery Environment provides a powerful and rich graphical interface to the iPlant Collaborative cyberinfrastructure by creating an accessible virtual workbench that enables all levels of expertise, ranging from students to traditional biology researchers and computational experts, to explore, analyze, and share their data. By providing access to iPlant's robust data-management system and high-performance computing resources, the Discovery Environment also creates a unified space in which researchers can access scalable tools. Researchers can use available Applications (Apps) to execute analyses on their data, as well as customize or integrate their own tools to better meet the specific needs of their research. These Apps can also be used in workflows that automate more complicated analyses. This module describes how to use the main features of the Discovery Environment, using bioinformatics workflows for high-throughput sequence data as examples. © 2013 by John Wiley & Sons, Inc.

Computer-Aided Drug Design (CADD): Methodological Aspects and Practical Applications in Cancer Research

NASA Astrophysics Data System (ADS)

Gianti, Eleonora

Computer-Aided Drug Design (CADD) has deservedly gained increasing popularity in modern drug discovery (Schneider, G.; Fechner, U. 2005), whether applied to academic basic research or the pharmaceutical industry pipeline. In this work, after reviewing theoretical advancements in CADD, we integrated novel and stateof- the-art methods to assist in the design of small-molecule inhibitors of current cancer drug targets, specifically: Androgen Receptor (AR), a nuclear hormone receptor required for carcinogenesis of Prostate Cancer (PCa); Signal Transducer and Activator of Transcription 5 (STAT5), implicated in PCa progression; and Epstein-Barr Nuclear Antigen-1 (EBNA1), essential to the Epstein Barr Virus (EBV) during latent infections. Androgen Receptor. With the aim of generating binding mode hypotheses for a class (Handratta, V.D. et al. 2005) of dual AR/CYP17 inhibitors (CYP17 is a key enzyme for androgens biosynthesis and therefore implicated in PCa development), we successfully implemented a receptor-based computational strategy based on flexible receptor docking (Gianti, E.; Zauhar, R.J. 2012). Then, with the ultimate goal of identifying novel AR binders, we performed Virtual Screening (VS) by Fragment-Based Shape Signatures, an improved version of the original method developed in our Laboratory (Zauhar, R.J. et al. 2003), and we used the results to fully assess the high-level performance of this innovative tool in computational chemistry. STAT5. The SRC Homology 2 (SH2) domain of STAT5 is responsible for phospho-peptide recognition and activation. As a keystone of Structure-Based Drug Design (SBDD), we characterized key residues responsible for binding. We also generated a model of STAT5 receptor bound to a phospho-peptide ligand, which was validated by docking publicly known STAT5 inhibitors. Then, we performed Shape Signatures- and docking-based VS of the ZINC database (zinc.docking.org), followed by Molecular Mechanics Generalized Born Surface Area (MMGBSA) simulations, paired with Principal Component Analysis (PCA) of top-scoring hits to identify novel lead molecules likely to be active against STAT5. EBNA1 is the only viral protein consistently expressed in the many EBV-associated tumors, and is required for viral genome maintenance during latent infection. To immediately assist SBDD, we computationally identified "druggable" binding sites of EBNA1, and our predictions were later confirmed by experimental evidence (The Wistar Institute proprietary data).

Computational Tools for Allosteric Drug Discovery: Site Identification and Focus Library Design.

PubMed

Huang, Wenkang; Nussinov, Ruth; Zhang, Jian

2017-01-01

Allostery is an intrinsic phenomenon of biological macromolecules involving regulation and/or signal transduction induced by a ligand binding to an allosteric site distinct from a molecule's active site. Allosteric drugs are currently receiving increased attention in drug discovery because drugs that target allosteric sites can provide important advantages over the corresponding orthosteric drugs including specific subtype selectivity within receptor families. Consequently, targeting allosteric sites, instead of orthosteric sites, can reduce drug-related side effects and toxicity. On the down side, allosteric drug discovery can be more challenging than traditional orthosteric drug discovery due to difficulties associated with determining the locations of allosteric sites and designing drugs based on these sites and the need for the allosteric effects to propagate through the structure, reach the ligand binding site and elicit a conformational change. In this study, we present computational tools ranging from the identification of potential allosteric sites to the design of "allosteric-like" modulator libraries. These tools may be particularly useful for allosteric drug discovery.

[30 years since the first AIDS cases were reported: history and the present. Part I].

PubMed

Brůcková, Marie

2012-05-01

The 30-year natural history of AIDS disease is presented from the first clinical cases reported in 1981 to the identification of the HIV as the etiological agent of the disease. The priority dispute between Robert C. Gallo and Luc Montagnier over the discovery of the human immunodeficiency virus is briefly addressed. The final confirmation of the French priority was provided by the fact that the Nobel Prize in Medicine 2008 was awarded to Luc Montagnier and Francoise Barré--Sinoussi from the Pasteur Institute in Paris.

Some Workplace Effects of CAD and CAM.

ERIC Educational Resources Information Center

Ebel, Karl-H.; Ulrich, Erhard

1987-01-01

Examines the impact of computer-aided design (CAD) and computer-aided manufacturing (CAM) on employment, work organization, working conditions, job content, training, and industrial relations in several countries. Finds little evidence of negative employment effects since productivity gains are offset by various compensatory factors. (Author/CH)

Society for College Science Teachers: High Technology.

ERIC Educational Resources Information Center

Menefee, Robert

1983-01-01

Presents findings of a study group on high technology charged with determining a definition, assessing current educational response, and examining implications for the future. Topics addressed include: super-techs; computer-aided design/computer-aided manufacture (CAD/CAM); structural unemployment; a two-plus-two curriculum; and educational…

The Power of Computer-aided Tomography to Investigate Marine Benthic Communities

EPA Science Inventory

Utilization of Computer-aided-Tomography (CT) technology is a powerful tool to investigate benthic communities in aquatic systems. In this presentation, we will attempt to summarize our 15 years of experience in developing specific CT methods and applications to marine benthic co...

A comparison of detection efficiency on an air traffic control monitoring task with and without computer aiding.

DOT National Transportation Integrated Search

1989-01-01

Future levels of air traffic control automation plan to incorporate computer aiding features designed to alert the controller to upcoming problem situations by displaying information that will identify the situation and suggest possible solutions. Co...

Microwave processing of a dental ceramic used in computer-aided design/computer-aided manufacturing.

PubMed

Pendola, Martin; Saha, Subrata

2015-01-01

Because of their favorable mechanical properties and natural esthetics, ceramics are widely used in restorative dentistry. The conventional ceramic sintering process required for their use is usually slow, however, and the equipment has an elevated energy consumption. Sintering processes that use microwaves have several advantages compared to regular sintering: shorter processing times, lower energy consumption, and the capacity for volumetric heating. The objective of this study was to test the mechanical properties of a dental ceramic used in computer-aided design/computer-aided manufacturing (CAD/CAM) after the specimens were processed with microwave hybrid sintering. Density, hardness, and bending strength were measured. When ceramic specimens were sintered with microwaves, the processing times were reduced and protocols were simplified. Hardness was improved almost 20% compared to regular sintering, and flexural strength measurements suggested that specimens were approximately 50% stronger than specimens sintered in a conventional system. Microwave hybrid sintering may preserve or improve the mechanical properties of dental ceramics designed for CAD/CAM processing systems, reducing processing and waiting times.

The effects of computer-aided design software on engineering students' spatial visualisation skills

NASA Astrophysics Data System (ADS)

Kösa, Temel; Karakuş, Fatih

2018-03-01

The purpose of this study was to determine the influence of computer-aided design (CAD) software-based instruction on the spatial visualisation skills of freshman engineering students in a computer-aided engineering drawing course. A quasi-experimental design was applied, using the Purdue Spatial Visualization Test-Visualization of Rotations (PSVT:R) for both the pre- and the post-test. The participants were 116 freshman students in the first year of their undergraduate programme in the Department of Mechanical Engineering at a university in Turkey. A total of 72 students comprised the experimental group; they were instructed with CAD-based activities in an engineering drawing course. The control group consisted of 44 students who did not attend this course. The results of the study showed that a CAD-based engineering drawing course had a positive effect on developing engineering students' spatial visualisation skills. Additionally, the results of the study showed that spatial visualisation skills can be a predictor for success in a computer-aided engineering drawing course.

[Computer aided design for fixed partial denture framework based on reverse engineering technology].

PubMed

Sun, Yu-chun; Lü, Pei-jun; Wang, Yong

2006-03-01

To explore a computer aided design (CAD) route for the framework of domestic fixed partial denture (FPD) and confirm the suitable method of 3-D CAD. The working area of a dentition model was scanned with a 3-D mechanical scanner. Using the reverse engineering (RE) software, margin and border curves were extracted and several reference curves were created to ensure the dimension and location of pontic framework that was taken from the standard database. The shoulder parts of the retainers were created after axial surfaces constructed. The connecting areas, axial line and curving surface of the framework connector were finally created. The framework of a three-unit FPD was designed with RE technology, which showed smooth surfaces and continuous contours. The design route is practical. The result of this study is significant in theory and practice, which will provide a reference for establishing the computer aided design/computer aided manufacture (CAD/CAM) system of domestic FPD.

Adhesive Bonding to Computer-aided Design/ Computer-aided Manufacturing Esthetic Dental Materials: An Overview.

PubMed

Awad, Mohamed Moustafa; Alqahtani, H; Al-Mudahi, A; Murayshed, M S; Alrahlah, A; Bhandi, Shilpa H

2017-07-01

To review the adhesive bonding to different computer-aided design/computer-aided manufacturing (CAD/CAM) esthetic restorative materials. The use of CAD/CAM esthetic restorative materials has gained popularity in recent years. Several CAD/ CAM esthetic restorative materials are commercially available. Adhesive bonding is a major determinant of success of CAD/ CAM restorations. Review result: An account of the currently available bonding strategies are discussed with their rationale in various CAD/ CAM materials. Different surface treatment methods as well as adhesion promoters can be used to achieve reliable bonding of CAD/CAM restorative materials. Selection of bonding strategy to such material is determined based on its composition. Further evidence is required to evaluate the effect of new surface treatment methods, such as nonthermal atmospheric plasma and self-etching ceramic primer on bonding to different dental ceramics. An understanding of the currently available bonding strategies to CA/CAM materials can help the clinician to select the most indicated system for each category of materials.

Utilizing computerized entertainment education in the development of decision aids for lower literate and naïve computer users.

PubMed

Jibaja-Weiss, Maria L; Volk, Robert J

2007-01-01

Decision aids have been developed by using various delivery methods, including interactive computer programs. Such programs, however, still rely heavily on written information, health and digital literacy, and reading ease. We describe an approach to overcome these potential barriers for low-literate, underserved populations by making design considerations for poor readers and naïve computer users and by using concepts from entertainment education to engage the user and to contextualize the content for the user. The system design goals are to make the program both didactic and entertaining and the navigation and graphical user interface as simple as possible. One entertainment education strategy, the soap opera, is linked seamlessly to interactive learning modules to enhance the content of the soap opera episodes. The edutainment decision aid model (EDAM) guides developers through the design process. Although designing patient decision aids that are educational, entertaining, and targeted toward poor readers and those with limited computer skills is a complex task, it is a promising strategy for aiding this population. Entertainment education may be a highly effective approach to promoting informed decision making for patients with low health literacy.

COMPUTER-AIDED DRAFTING AND DESIGN, A THREE-WEEK SUMMER INSTITUTE TRAINING PROGRAM (MIAMI-DADE JUNIOR COLLEGE, MIAMI, FLORIDA, JULY 10, 1967 - JULY 28, 1967). FINAL REPORT.

ERIC Educational Resources Information Center

MORPHONIOS, ALEX G.

THIRTY-SIX INSTRUCTORS, SUPERVISORS, AND DEPARTMENT CHAIRMEN IN AREAS OF DRAFTING, ENGINEERING, MANUFACTURING, AND COMPUTER TECHNOLOGY AT JUNIOR COLLEGES, TECHNICAL, AND AREA VOCATIONAL SCHOOLS IN 20 STATES ATTENDED A 3-WEEK SUMMER INSTITUTE TRAINING PROGRAM ON COMPUTER-AIDED DRAFTING AND DESIGN. EXPERIENCE IN PROGRAMING THE IBM SYSTEM 1620 WITH…

A Study of the Use of Ontologies for Building Computer-Aided Control Engineering Self-Learning Educational Software

ERIC Educational Resources Information Center

García, Isaías; Benavides, Carmen; Alaiz, Héctor; Alonso, Angel

2013-01-01

This paper describes research on the use of knowledge models (ontologies) for building computer-aided educational software in the field of control engineering. Ontologies are able to represent in the computer a very rich conceptual model of a given domain. This model can be used later for a number of purposes in different software applications. In…

Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery

PubMed Central

Sykes, Melissa L.; Jones, Amy J.; Shelper, Todd B.; Simpson, Moana; Lang, Rebecca; Poulsen, Sally-Ann; Sleebs, Brad E.

2017-01-01

ABSTRACT Open-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open-access Pathogen Box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. We tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages in vitro. Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease, and leishmaniasis drug discovery efforts have been identified. Inclusive of this in vitro biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open-source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research. PMID:28674055

Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery.

PubMed

Duffy, Sandra; Sykes, Melissa L; Jones, Amy J; Shelper, Todd B; Simpson, Moana; Lang, Rebecca; Poulsen, Sally-Ann; Sleebs, Brad E; Avery, Vicky M

2017-09-01

Open-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open-access Pathogen Box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. We tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages in vitro Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease, and leishmaniasis drug discovery efforts have been identified. Inclusive of this in vitro biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open-source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research. Copyright © 2017 Duffy et al.

Contributing, Exchanging and Linking for Learning: Supporting Web Co-Discovery in One-to-One Environments

ERIC Educational Resources Information Center

Liu, Chen-Chung; Don, Ping-Hsing; Chung, Chen-Wei; Lin, Shao-Jun; Chen, Gwo-Dong; Liu, Baw-Jhiune

2010-01-01

While Web discovery is usually undertaken as a solitary activity, Web co-discovery may transform Web learning activities from the isolated individual search process into interactive and collaborative knowledge exploration. Recent studies have proposed Web co-search environments on a single computer, supported by multiple one-to-one technologies.…

Modeling and Analysis of Power Processing Systems (MAPPS). Volume 1: Technical report

NASA Technical Reports Server (NTRS)

Lee, F. C.; Rahman, S.; Carter, R. A.; Wu, C. H.; Yu, Y.; Chang, R.

1980-01-01

Computer aided design and analysis techniques were applied to power processing equipment. Topics covered include: (1) discrete time domain analysis of switching regulators for performance analysis; (2) design optimization of power converters using augmented Lagrangian penalty function technique; (3) investigation of current-injected multiloop controlled switching regulators; and (4) application of optimization for Navy VSTOL energy power system. The generation of the mathematical models and the development and application of computer aided design techniques to solve the different mathematical models are discussed. Recommendations are made for future work that would enhance the application of the computer aided design techniques for power processing systems.

Creation of Anatomically Accurate Computer-Aided Design (CAD) Solid Models from Medical Images

NASA Technical Reports Server (NTRS)

Stewart, John E.; Graham, R. Scott; Samareh, Jamshid A.; Oberlander, Eric J.; Broaddus, William C.

1999-01-01

Most surgical instrumentation and implants used in the world today are designed with sophisticated Computer-Aided Design (CAD)/Computer-Aided Manufacturing (CAM) software. This software automates the mechanical development of a product from its conceptual design through manufacturing. CAD software also provides a means of manipulating solid models prior to Finite Element Modeling (FEM). Few surgical products are designed in conjunction with accurate CAD models of human anatomy because of the difficulty with which these models are created. We have developed a novel technique that creates anatomically accurate, patient specific CAD solids from medical images in a matter of minutes.

Computer-aided light sheet flow visualization using photogrammetry

NASA Technical Reports Server (NTRS)

Stacy, Kathryn; Severance, Kurt; Childers, Brooks A.

1994-01-01

A computer-aided flow visualization process has been developed to analyze video images acquired from rotating and translating light sheet visualization systems. The computer process integrates a mathematical model for image reconstruction, advanced computer graphics concepts, and digital image processing to provide a quantitative and a visual analysis capability. The image reconstruction model, based on photogrammetry, uses knowledge of the camera and light sheet locations and orientations to project two-dimensional light sheet video images into three-dimensional space. A sophisticated computer visualization package, commonly used to analyze computational fluid dynamics (CFD) results, was chosen to interactively display the reconstructed light sheet images with the numerical surface geometry for the model or aircraft under study. The photogrammetric reconstruction technique and the image processing and computer graphics techniques and equipment are described. Results of the computer-aided process applied to both a wind tunnel translating light sheet experiment and an in-flight rotating light sheet experiment are presented. The capability to compare reconstructed experimental light sheet images with CFD solutions in the same graphics environment is also demonstrated.

Computer-Aided Light Sheet Flow Visualization

NASA Technical Reports Server (NTRS)

Stacy, Kathryn; Severance, Kurt; Childers, Brooks A.

1993-01-01

A computer-aided flow visualization process has been developed to analyze video images acquired from rotating and translating light sheet visualization systems. The computer process integrates a mathematical model for image reconstruction, advanced computer graphics concepts, and digital image processing to provide a quantitative and visual analysis capability. The image reconstruction model, based on photogrammetry, uses knowledge of the camera and light sheet locations and orientations to project two-dimensional light sheet video images into three-dimensional space. A sophisticated computer visualization package, commonly used to analyze computational fluid dynamics (CFD) data sets, was chosen to interactively display the reconstructed light sheet images, along with the numerical surface geometry for the model or aircraft under study. A description is provided of the photogrammetric reconstruction technique, and the image processing and computer graphics techniques and equipment. Results of the computer aided process applied to both a wind tunnel translating light sheet experiment and an in-flight rotating light sheet experiment are presented. The capability to compare reconstructed experimental light sheet images and CFD solutions in the same graphics environment is also demonstrated.

Computer-aided light sheet flow visualization

NASA Technical Reports Server (NTRS)

Stacy, Kathryn; Severance, Kurt; Childers, Brooks A.

1993-01-01

A computer-aided flow visualization process has been developed to analyze video images acquired from rotating and translating light sheet visualization systems. The computer process integrates a mathematical model for image reconstruction, advanced computer graphics concepts, and digital image processing to provide a quantitative and visual analysis capability. The image reconstruction model, based on photogrammetry, uses knowledge of the camera and light sheet locations and orientations to project two-dimensional light sheet video images into three-dimensional space. A sophisticated computer visualization package, commonly used to analyze computational fluid dynamics (CFD) data sets, was chosen to interactively display the reconstructed light sheet images, along with the numerical surface geometry for the model or aircraft under study. A description is provided of the photogrammetric reconstruction technique, and the image processing and computer graphics techniques and equipment. Results of the computer aided process applied to both a wind tunnel translating light sheet experiment and an in-flight rotating light sheet experiment are presented. The capability to compare reconstructed experimental light sheet images and CFD solutions in the same graphics environment is also demonstrated.

Reduced Face Identity Aftereffects in Relatives of Children with Autism

ERIC Educational Resources Information Center

Fiorentini, Chiara; Gray, Laura; Rhodes, Gillian; Jeffery, Linda; Pellicano, Elizabeth

2012-01-01

Autism is a pervasive developmental condition with complex aetiology. To aid the discovery of genetic mechanisms, researchers have turned towards identifying potential endophenotypes--subtle neurobiological or neurocognitive traits present in individuals with autism and their "unaffected" relatives. Previous research has shown that relatives of…

CAD/CAM complete dentures: a review of two commercial fabrication systems.

PubMed

Kattadiyil, Mathew T; Goodacre, Charles J; Baba, Nadim Z

2013-06-01

The use of computer-aided design and computer-aided manufacturing (CAD/CAM) has become available for complete dentures through the AvaDent and Dentca systems. AvaDent uses laser scanning and computer technology. Teeth are arranged and bases formed using proprietary software.The bases are milled from prepolymerized pucks of resin. Dentca uses computer software to produce virtual maxillary and mandibular edentulous ridges, arrange the teeth and form bases. The dentures are fabricated using a conventional processing technique.

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

NASA Technical Reports Server (NTRS)

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.

Computer-Aided Communication Satellite System Analysis and Optimization.

ERIC Educational Resources Information Center

Stagl, Thomas W.; And Others

Various published computer programs for fixed/broadcast communication satellite system synthesis and optimization are discussed. The rationale for selecting General Dynamics/Convair's Satellite Telecommunication Analysis and Modeling Program (STAMP) in modified form to aid in the system costing and sensitivity analysis work in the Program on…

Challenges facing developers of CAD/CAM models that seek to predict human working postures

NASA Astrophysics Data System (ADS)

Wiker, Steven F.

2005-11-01

This paper outlines the need for development of human posture prediction models for Computer Aided Design (CAD) and Computer Aided Manufacturing (CAM) design applications in product, facility and work design. Challenges facing developers of posture prediction algorithms are presented and discussed.

A Prototype of CAD/CAM Education in the Community College.

ERIC Educational Resources Information Center

Kimmey, James R.

Drawing upon Elgin Community College's (ECC's) 7-year history of program development and operation, this paper demonstrates how ECC, in cooperation with Northern Illinois Industries, Computervision Corporation, Mazak Corporation, and the Society of Manufacturing Engineers, established a Computer-Aided Design and Drafting/Computer-Aided Machining…

A Structure for Creating Quality Software.

ERIC Educational Resources Information Center

Christensen, Larry C.; Bodey, Michael R.

1990-01-01

Addresses the issue of assuring quality software for use in computer-aided instruction and presents a structure by which developers can create quality courseware. Differences between courseware and computer-aided instruction software are discussed, methods for testing software are described, and human factors issues as well as instructional design…

SMART USE OF COMPUTER-AIDED SPERM ANALYSIS (CASA) TO CHARACTERIZE SPERM MOTION

EPA Science Inventory

Computer-aided sperm analysis (CASA) has evolved over the past fifteen years to provide an objective, practical means of measuring and characterizing the velocity and parttern of sperm motion. CASA instruments use video frame-grabber boards to capture multiple images of spermato...

Calendar Instruments in Retrospective Web Surveys

ERIC Educational Resources Information Center

Glasner, Tina; van der Vaart, Wander; Dijkstra, Wil

2015-01-01

Calendar instruments incorporate aided recall techniques such as temporal landmarks and visual time lines that aim to reduce response error in retrospective surveys. Those calendar instruments have been used extensively in off-line research (e.g., computer-aided telephone interviews, computer assisted personal interviewing, and paper and pen…

DEVELOPMENT AND USE OF COMPUTER-AIDED PROCESS ENGINEERING TOOLS FOR POLLUTION PREVENTION

EPA Science Inventory

The use of Computer-Aided Process Engineering (CAPE) and process simulation tools has become established industry practice to predict simulation software, new opportunities are available for the creation of a wide range of ancillary tools that can be used from within multiple sim...

Meaning and purpose in the lives of persons with AIDS.

PubMed

Coward, D D

1994-10-01

Little research has been reported that explores meaning-discovery and meaning-making in persons with AIDS. Self-transcendence experiences, as proposed by Reed (1991), may lead to maintenance or restoration of mental health in persons facing end-of-life issues. Nurses who work with persons with life-threatening illness, such as men and women with AIDS, have opportunities to facilitate choices that lead to experiences from which meaning and emotional well-being may be obtained. This study used a phenomenological approach to describe experiences of 10 men and 10 women with AIDS that led to feelings of increased self-worth, purpose, and meaning in their lives. Participants provided oral or written descriptions of experiences associated with feelings of increased connectedness with others, sense of well-being, and hope for longer life. Data were analyzed using Colaizzi's phenomenological technique (1978). Although men and women with AIDS faced some of the same issues, their responses were different. By incorporating gender and individual differences, nurses may be better able to create therapeutic exchanges in which self-transcendence views and behaviors are fostered in both men and women with AIDS.

The NASA computer aided design and test system

NASA Technical Reports Server (NTRS)

Gould, J. M.; Juergensen, K.

1973-01-01

A family of computer programs facilitating the design, layout, evaluation, and testing of digital electronic circuitry is described. CADAT (computer aided design and test system) is intended for use by NASA and its contractors and is aimed predominantly at providing cost effective microelectronic subsystems based on custom designed metal oxide semiconductor (MOS) large scale integrated circuits (LSIC's). CADAT software can be easily adopted by installations with a wide variety of computer hardware configurations. Its structure permits ease of update to more powerful component programs and to newly emerging LSIC technologies. The components of the CADAT system are described stressing the interaction of programs rather than detail of coding or algorithms. The CADAT system provides computer aids to derive and document the design intent, includes powerful automatic layout software, permits detailed geometry checks and performance simulation based on mask data, and furnishes test pattern sequences for hardware testing.

An algorithm of discovering signatures from DNA databases on a computer cluster.

PubMed

Lee, Hsiao Ping; Sheu, Tzu-Fang

2014-10-05

Signatures are short sequences that are unique and not similar to any other sequence in a database that can be used as the basis to identify different species. Even though several signature discovery algorithms have been proposed in the past, these algorithms require the entirety of databases to be loaded in the memory, thus restricting the amount of data that they can process. It makes those algorithms unable to process databases with large amounts of data. Also, those algorithms use sequential models and have slower discovery speeds, meaning that the efficiency can be improved. In this research, we are debuting the utilization of a divide-and-conquer strategy in signature discovery and have proposed a parallel signature discovery algorithm on a computer cluster. The algorithm applies the divide-and-conquer strategy to solve the problem posed to the existing algorithms where they are unable to process large databases and uses a parallel computing mechanism to effectively improve the efficiency of signature discovery. Even when run with just the memory of regular personal computers, the algorithm can still process large databases such as the human whole-genome EST database which were previously unable to be processed by the existing algorithms. The algorithm proposed in this research is not limited by the amount of usable memory and can rapidly find signatures in large databases, making it useful in applications such as Next Generation Sequencing and other large database analysis and processing. The implementation of the proposed algorithm is available at http://www.cs.pu.edu.tw/~fang/DDCSDPrograms/DDCSD.htm.

Research on computer aided testing of pilot response to critical in-flight events

NASA Technical Reports Server (NTRS)

Giffin, W. C.; Rockwell, T. H.; Smith, P. J.

1984-01-01

Experiments on pilot decision making are described. The development of models of pilot decision making in critical in flight events (CIFE) are emphasized. The following tests are reported on the development of: (1) a frame system representation describing how pilots use their knowledge in a fault diagnosis task; (2) assessment of script norms, distance measures, and Markov models developed from computer aided testing (CAT) data; and (3) performance ranking of subject data. It is demonstrated that interactive computer aided testing either by touch CRT's or personal computers is a useful research and training device for measuring pilot information management in diagnosing system failures in simulated flight situations. Performance is dictated by knowledge of aircraft sybsystems, initial pilot structuring of the failure symptoms and efficient testing of plausible causal hypotheses.

The role of fragment-based and computational methods in polypharmacology.

PubMed

Bottegoni, Giovanni; Favia, Angelo D; Recanatini, Maurizio; Cavalli, Andrea

2012-01-01

Polypharmacology-based strategies are gaining increased attention as a novel approach to obtaining potentially innovative medicines for multifactorial diseases. However, some within the pharmaceutical community have resisted these strategies because they can be resource-hungry in the early stages of the drug discovery process. Here, we report on fragment-based and computational methods that might accelerate and optimize the discovery of multitarget drugs. In particular, we illustrate that fragment-based approaches can be particularly suited for polypharmacology, owing to the inherent promiscuous nature of fragments. In parallel, we explain how computer-assisted protocols can provide invaluable insights into how to unveil compounds theoretically able to bind to more than one protein. Furthermore, several pragmatic aspects related to the use of these approaches are covered, thus offering the reader practical insights on multitarget-oriented drug discovery projects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reader error, object recognition, and visual search

NASA Astrophysics Data System (ADS)

Kundel, Harold L.

2004-05-01

Small abnormalities such as hairline fractures, lung nodules and breast tumors are missed by competent radiologists with sufficient frequency to make them a matter of concern to the medical community; not only because they lead to litigation but also because they delay patient care. It is very easy to attribute misses to incompetence or inattention. To do so may be placing an unjustified stigma on the radiologists involved and may allow other radiologists to continue a false optimism that it can never happen to them. This review presents some of the fundamentals of visual system function that are relevant to understanding the search for and the recognition of small targets embedded in complicated but meaningful backgrounds like chests and mammograms. It presents a model for visual search that postulates a pre-attentive global analysis of the retinal image followed by foveal checking fixations and eventually discovery scanning. The model will be used to differentiate errors of search, recognition and decision making. The implications for computer aided diagnosis and for functional workstation design are discussed.

Mechanistic insights into chemical and photochemical transformations of bismuth vanadate photoanodes

DOE PAGES

Toma, Francesca M.; Cooper, Jason K.; Kunzelmann, Viktoria; ...

2016-07-05

Artificial photosynthesis relies on the availability of semiconductors that are chemically stable and can efficiently capture solar energy. Although metal oxide semiconductors have been investigated for their promise to resist oxidative attack, materials in this class can suffer from chemical and photochemical instability. Here we present a methodology for evaluating corrosion mechanisms and apply it to bismuth vanadate, a state-of-the-art photoanode. Analysis of changing morphology and composition under solar water splitting conditions reveals chemical instabilities that are not predicted from thermodynamic considerations of stable solid oxide phases, as represented by the Pourbaix diagram for the system. Computational modelling indicates thatmore » photoexcited charge carriers accumulated at the surface destabilize the lattice, and that self-passivation by formation of a chemically stable surface phase is kinetically hindered. Although chemical stability of metal oxides cannot be assumed, insight into corrosion mechanisms aids development of protection strategies and discovery of semiconductors with improved stability.« less

Improving quantitative structure-activity relationship models using Artificial Neural Networks trained with dropout.

PubMed

Mendenhall, Jeffrey; Meiler, Jens

2016-02-01

Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both enrichment false positive rate and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22-46 % over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods.

Improving Quantitative Structure-Activity Relationship Models using Artificial Neural Networks Trained with Dropout

PubMed Central

Mendenhall, Jeffrey; Meiler, Jens

2016-01-01

Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery (LB-CADD) pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both Enrichment false positive rate (FPR) and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22–46% over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods. PMID:26830599

Translational Radiomics: Defining the Strategy Pipeline and Considerations for Application-Part 2: From Clinical Implementation to Enterprise.

PubMed

Shaikh, Faiq; Franc, Benjamin; Allen, Erastus; Sala, Evis; Awan, Omer; Hendrata, Kenneth; Halabi, Safwan; Mohiuddin, Sohaib; Malik, Sana; Hadley, Dexter; Shrestha, Rasu

2018-03-01

Enterprise imaging has channeled various technological innovations to the field of clinical radiology, ranging from advanced imaging equipment and postacquisition iterative reconstruction tools to image analysis and computer-aided detection tools. More recently, the advancement in the field of quantitative image analysis coupled with machine learning-based data analytics, classification, and integration has ushered in the era of radiomics, a paradigm shift that holds tremendous potential in clinical decision support as well as drug discovery. However, there are important issues to consider to incorporate radiomics into a clinically applicable system and a commercially viable solution. In this two-part series, we offer insights into the development of the translational pipeline for radiomics from methodology to clinical implementation (Part 1) and from that point to enterprise development (Part 2). In Part 2 of this two-part series, we study the components of the strategy pipeline, from clinical implementation to building enterprise solutions. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Development and Verification of Body Armor Target Geometry Created Using Computed Tomography Scans

DTIC Science & Technology

2017-07-13

designated by other authorized documents. Citation of manufacturer’s or trade names does not constitute an official endorsement or approval of...modeling consisted of manual measurement of armor systems and translating those measurements to computer-aided design geometry, which can be tedious and...computer-aided design (CAD) human geometry model (referred to throughout as ORCA man) that is used in the Operational Requirement-based Casualty Assessment

Making Ceramic/Polymer Parts By Extrusion Stereolithography

NASA Technical Reports Server (NTRS)

Stuffle, Kevin; Mulligan, A.; Creegan, P.; Boulton, J. M.; Lombardi, J. L.; Calvert, P. D.

1996-01-01

Extrusion stereolithography developmental method of computer-controlled manufacturing of objects out of ceramic/polymer composite materials. Computer-aided design/computer-aided manufacturing (CAD/CAM) software used to create image of desired part and translate image into motion commands for combination of mechanisms moving resin dispenser. Extrusion performed in coordination with motion of dispenser so buildup of extruded material takes on size and shape of desired part. Part thermally cured after deposition.

Manufacturing Methods and Technology Project Summary Reports

DTIC Science & Technology

1985-06-01

Computer -Aided Design (CAD)/ Computer -Aided Manufacturing (CAM) Process for the Production of Cold Forged Gears Project 483 6121 - Robotic Welding and...Caliber Projectile Bodies Project 682 8370 - Automatic Inspection and 1-I1 Process Control of Weapons Parts Manufacturing METALS Project 181 7285 - Cast...designed for use on each project. Experience suggested that a general purpose computer interface might be designed that could be used on any project

User's manual: Computer-aided design programs for inductor-energy-storage dc-to-dc electronic power converters

NASA Technical Reports Server (NTRS)

Huffman, S.

1977-01-01

Detailed instructions on the use of two computer-aided-design programs for designing the energy storage inductor for single winding and two winding dc to dc converters are provided. Step by step procedures are given to illustrate the formatting of user input data. The procedures are illustrated by eight sample design problems which include the user input and the computer program output.

Basic research and 12 years of clinical experience in computer-assisted navigation technology: a review.

PubMed

Ewers, R; Schicho, K; Undt, G; Wanschitz, F; Truppe, M; Seemann, R; Wagner, A

2005-01-01

Computer-aided surgical navigation technology is commonly used in craniomaxillofacial surgery. It offers substantial improvement regarding esthetic and functional aspects in a range of surgical procedures. Based on augmented reality principles, where the real operative site is merged with computer generated graphic information, computer-aided navigation systems were employed, among other procedures, in dental implantology, arthroscopy of the temporomandibular joint, osteotomies, distraction osteogenesis, image guided biopsies and removals of foreign bodies. The decision to perform a procedure with or without computer-aided intraoperative navigation depends on the expected benefit to the procedure as well as on the technical expenditure necessary to achieve that goal. This paper comprises the experience gained in 12 years of research, development and routine clinical application. One hundred and fifty-eight operations with successful application of surgical navigation technology--divided into five groups--are evaluated regarding the criteria "medical benefit" and "technical expenditure" necessary to perform these procedures. Our results indicate that the medical benefit is likely to outweight the expenditure of technology with few exceptions (calvaria transplant, resection of the temporal bone, reconstruction of the orbital floor). Especially in dental implantology, specialized software reduces time and additional costs necessary to plan and perform procedures with computer-aided surgical navigation.

Topology optimization aided structural design: Interpretation, computational aspects and 3D printing.

PubMed

Kazakis, Georgios; Kanellopoulos, Ioannis; Sotiropoulos, Stefanos; Lagaros, Nikos D

2017-10-01

Construction industry has a major impact on the environment that we spend most of our life. Therefore, it is important that the outcome of architectural intuition performs well and complies with the design requirements. Architects usually describe as "optimal design" their choice among a rather limited set of design alternatives, dictated by their experience and intuition. However, modern design of structures requires accounting for a great number of criteria derived from multiple disciplines, often of conflicting nature. Such criteria derived from structural engineering, eco-design, bioclimatic and acoustic performance. The resulting vast number of alternatives enhances the need for computer-aided architecture in order to increase the possibility of arriving at a more preferable solution. Therefore, the incorporation of smart, automatic tools in the design process, able to further guide designer's intuition becomes even more indispensable. The principal aim of this study is to present possibilities to integrate automatic computational techniques related to topology optimization in the phase of intuition of civil structures as part of computer aided architectural design. In this direction, different aspects of a new computer aided architectural era related to the interpretation of the optimized designs, difficulties resulted from the increased computational effort and 3D printing capabilities are covered here in.

Visual and computer software-aided estimates of Dupuytren's contractures: correlation with clinical goniometric measurements.

PubMed

Smith, R P; Dias, J J; Ullah, A; Bhowal, B

2009-05-01

Corrective surgery for Dupuytren's disease represents a significant proportion of a hand surgeon's workload. The decision to go ahead with surgery and the success of surgery requires measuring the degree of contracture of the diseased finger(s). This is performed in clinic with a goniometer, pre- and postoperatively. Monitoring the recurrence of the contracture can inform on surgical outcome, research and audit. We compared visual and computer software-aided estimation of Dupuytren's contractures to clinical goniometric measurements in 60 patients with Dupuytren's disease. Patients' hands were digitally photographed. There were 76 contracted finger joints--70 proximal interphalangeal joints and six distal interphalangeal joints. The degrees of contracture of these images were visually assessed by six orthopaedic staff of differing seniority and re-assessed with computer software. Across assessors, the Pearson correlation between the goniometric measurements and the visual estimations was 0.83 and this significantly improved to 0.88 with computer software. Reliability with intra-class correlations achieved 0.78 and 0.92 for the visual and computer-aided estimations, respectively, and with test-retest analysis, 0.92 for visual estimation and 0.95 for computer-aided measurements. Visual estimations of Dupuytren's contractures correlate well with actual clinical goniometric measurements and improve further if measured with computer software. Digital images permit monitoring of contracture after surgery and may facilitate research into disease progression and auditing of surgical technique.

Evaluation and Assessment of a Biomechanics Computer-Aided Instruction.

ERIC Educational Resources Information Center

Washington, N.; Parnianpour, M.; Fraser, J. M.

1999-01-01

Describes the Biomechanics Tutorial, a computer-aided instructional tool that was developed at Ohio State University to expedite the transition from lecture to application for undergraduate students. Reports evaluation results that used statistical analyses and student questionnaires to show improved performance on posttests as well as positive…

Computer Aided Reference Services in the Academic Library: Experiences in Organizing and Operating an Online Reference Service.

ERIC Educational Resources Information Center

Hoover, Ryan E.

1979-01-01

Summarizes the development of the Computer-Aided Reference Services (CARS) division of the University of Utah Libraries' reference department. Development, organizational structure, site selection, equipment, management, staffing and training considerations, promotion and marketing, budget and pricing, record keeping, statistics, and evaluation…

The Use of Computers to Aid Instruction in Beginning Chemistry

ERIC Educational Resources Information Center

Grandey, Robert C.

1971-01-01

Describes computer-aided lessons for determining chemical formulas from composition by weight, quantities from chemical equations, and balancing equations for oxidation-reduction reactions. Lessons were developed and used on the PLATO system at the University of Illinois. A brief analysis of student attitudes and of effectiveness of the programs…