Rester, Ulrich
2008-07-01
Drug discovery and development is an interdisciplinary, expensive and time-consuming process. Scientific advancements during the past two decades have altered the way pharmaceutical research produces novel bio-active molecules. Advances in computational techniques and hardware solutions have enabled in silico methods, and in particular virtual screening, to speed up modern lead identification and lead optimization. Recent successes have proven the power of combining virtual screening with complementary and synergistic biophysical methods, such as X-ray crystallography, NMR spectroscopy and isothermal titration calorimetry (ITC). This review addresses key issues, challenges and recent improvements of virtual screening methods and strategies. Examples highlighting the impact of an integrated virtual screening and biophysical characterization platform in the lead identification and optimization process are presented and discussed.
Approaches to virtual screening and screening library selection.
Wildman, Scott A
2013-01-01
The ease of access to virtual screening (VS) software in recent years has resulted in a large increase in literature reports. Over 300 publications in the last year report the use of virtual screening techniques to identify new chemical matter or present the development of new virtual screening techniques. The increased use is accompanied by a corresponding increase in misuse and misinterpretation of virtual screening results. This review aims to identify many of the common difficulties associated with virtual screening and allow researchers to better assess the reliability of their virtual screening effort.
Design and Development of ChemInfoCloud: An Integrated Cloud Enabled Platform for Virtual Screening.
Karthikeyan, Muthukumarasamy; Pandit, Deepak; Bhavasar, Arvind; Vyas, Renu
2015-01-01
The power of cloud computing and distributed computing has been harnessed to handle vast and heterogeneous data required to be processed in any virtual screening protocol. A cloud computing platorm ChemInfoCloud was built and integrated with several chemoinformatics and bioinformatics tools. The robust engine performs the core chemoinformatics tasks of lead generation, lead optimisation and property prediction in a fast and efficient manner. It has also been provided with some of the bioinformatics functionalities including sequence alignment, active site pose prediction and protein ligand docking. Text mining, NMR chemical shift (1H, 13C) prediction and reaction fingerprint generation modules for efficient lead discovery are also implemented in this platform. We have developed an integrated problem solving cloud environment for virtual screening studies that also provides workflow management, better usability and interaction with end users using container based virtualization, OpenVz.
1001 Ways to run AutoDock Vina for virtual screening
Jaghoori, Mohammad Mahdi; Bleijlevens, Boris; Olabarriaga, Silvia D.
2016-01-01
Large-scale computing technologies have enabled high-throughput virtual screening involving thousands to millions of drug candidates. It is not trivial, however, for biochemical scientists to evaluate the technical alternatives and their implications for running such large experiments. Besides
A web-based platform for virtual screening.
Watson, Paul; Verdonk, Marcel; Hartshorn, Michael J
2003-09-01
A fully integrated, web-based, virtual screening platform has been developed to allow rapid virtual screening of large numbers of compounds. ORACLE is used to store information at all stages of the process. The system includes a large database of historical compounds from high throughput screenings (HTS) chemical suppliers, ATLAS, containing over 3.1 million unique compounds with their associated physiochemical properties (ClogP, MW, etc.). The database can be screened using a web-based interface to produce compound subsets for virtual screening or virtual library (VL) enumeration. In order to carry out the latter task within ORACLE a reaction data cartridge has been developed. Virtual libraries can be enumerated rapidly using the web-based interface to the cartridge. The compound subsets can be seamlessly submitted for virtual screening experiments, and the results can be viewed via another web-based interface allowing ad hoc querying of the virtual screening data stored in ORACLE.
Novel Data Mining Methods for Virtual Screening of Biological Active Chemical Compounds
Soufan, Othman M.
2016-11-23
Drug discovery is a process that takes many years and hundreds of millions of dollars to reveal a confident conclusion about a specific treatment. Part of this sophisticated process is based on preliminary investigations to suggest a set of chemical compounds as candidate drugs for the treatment. Computational resources have been playing a significant role in this part through a step known as virtual screening. From a data mining perspective, availability of rich data resources is key in training prediction models. Yet, the difficulties imposed by big expansion in data and its dimensionality are inevitable. In this thesis, I address the main challenges that come when data mining techniques are used for virtual screening. In order to achieve an efficient virtual screening using data mining, I start by addressing the problem of feature selection and provide analysis of best ways to describe a chemical compound for an enhanced screening performance. High-throughput screening (HTS) assays data used for virtual screening are characterized by a great class imbalance. To handle this problem of class imbalance, I suggest using a novel algorithm called DRAMOTE to narrow down promising candidate chemicals aimed at interaction with specific molecular targets before they are experimentally evaluated. Existing works are mostly proposed for small-scale virtual screening based on making use of few thousands of interactions. Thus, I propose enabling large-scale (or big) virtual screening through learning millions of interaction while exploiting any relevant dependency for a better accuracy. A novel solution called DRABAL that incorporates structure learning of a Bayesian Network as a step to model dependency between the HTS assays, is showed to achieve significant improvements over existing state-of-the-art approaches.
Virtual screening of compound libraries.
Cerqueira, Nuno M F S A; Sousa, Sérgio F; Fernandes, Pedro A; Ramos, Maria João
2009-01-01
During the last decade, Virtual Screening (VS) has definitively established itself as an important part of the drug discovery and development process. VS involves the selection of likely drug candidates from large libraries of chemical structures by using computational methodologies, but the generic definition of VS encompasses many different methodologies. This chapter provides an introduction to the field by reviewing a variety of important aspects, including the different types of virtual screening methods, and the several steps required for a successful virtual screening campaign within a state-of-the-art approach, from target selection to postfilter application. This analysis is further complemented with a small collection important VS success stories.
Hierarchical virtual screening approaches in small molecule drug discovery.
Kumar, Ashutosh; Zhang, Kam Y J
2015-01-01
Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery. Copyright © 2014 Elsevier Inc. All rights reserved.
Structure-Based Virtual Screening of Commercially Available Compound Libraries.
Kireev, Dmitri
2016-01-01
Virtual screening (VS) is an efficient hit-finding tool. Its distinctive strength is that it allows one to screen compound libraries that are not available in the lab. Moreover, structure-based (SB) VS also enables an understanding of how the hit compounds bind the protein target, thus laying ground work for the rational hit-to-lead progression. SBVS requires a very limited experimental effort and is particularly well suited for academic labs and small biotech companies that, unlike pharmaceutical companies, do not have physical access to quality small-molecule libraries. Here, we describe SBVS of commercial compound libraries for Mer kinase inhibitors. The screening protocol relies on the docking algorithm Glide complemented by a post-docking filter based on structural protein-ligand interaction fingerprints (SPLIF).
Exploiting PubChem for Virtual Screening.
Xie, Xiang-Qun
2010-12-01
IMPORTANCE OF THE FIELD: PubChem is a public molecular information repository, a scientific showcase of the NIH Roadmap Initiative. The PubChem database holds over 27 million records of unique chemical structures of compounds (CID) derived from nearly 70 million substance depositions (SID), and contains more than 449,000 bioassay records with over thousands of in vitro biochemical and cell-based screening bioassays established, with targeting more than 7000 proteins and genes linking to over 1.8 million of substances. AREAS COVERED IN THIS REVIEW: This review builds on recent PubChem-related computational chemistry research reported by other authors while providing readers with an overview of the PubChem database, focusing on its increasing role in cheminformatics, virtual screening and toxicity prediction modeling. WHAT THE READER WILL GAIN: These publicly available datasets in PubChem provide great opportunities for scientists to perform cheminformatics and virtual screening research for computer-aided drug design. However, the high volume and complexity of the datasets, in particular the bioassay-associated false positives/negatives and highly imbalanced datasets in PubChem, also creates major challenges. Several approaches regarding the modeling of PubChem datasets and development of virtual screening models for bioactivity and toxicity predictions are also reviewed. TAKE HOME MESSAGE: Novel data-mining cheminformatics tools and virtual screening algorithms are being developed and used to retrieve, annotate and analyze the large-scale and highly complex PubChem biological screening data for drug design.
Automated recycling of chemistry for virtual screening and library design.
Vainio, Mikko J; Kogej, Thierry; Raubacher, Florian
2012-07-23
An early stage drug discovery project needs to identify a number of chemically diverse and attractive compounds. These hit compounds are typically found through high-throughput screening campaigns. The diversity of the chemical libraries used in screening is therefore important. In this study, we describe a virtual high-throughput screening system called Virtual Library. The system automatically "recycles" validated synthetic protocols and available starting materials to generate a large number of virtual compound libraries, and allows for fast searches in the generated libraries using a 2D fingerprint based screening method. Virtual Library links the returned virtual hit compounds back to experimental protocols to quickly assess the synthetic accessibility of the hits. The system can be used as an idea generator for library design to enrich the screening collection and to explore the structure-activity landscape around a specific active compound.
Virtual colonoscopy - changes for screening examination?
International Nuclear Information System (INIS)
Rust, G.F.; Reiser, M.
2002-01-01
In principle, virtual colonoscopy is capable to be used as method for early detection of colorectal cancer (CRC), even if the accuracy of the method and radiation exposure are matters discussion in the radiological community. Virtual colonoscopy is able to detect any pathology which is relevant for early detection of CRC especially when using multislice CT, but also with single slice CT. The diagnosis of small lesions, less than 7 mm in diameter (polyps and flat lesions) is still problematic as it is in conventional colonoscopy. The exposure to x-rays in asymptomatic patients, without any increased risk of developing cancer is highly problematic and should be reduced to a minimum. Using special post processing filters on the volume dataset it can be shown that a tube current of 20 mAs is sufficient without any loss in accuracy. Measurements on the Alderson-phantom showed, that an effective dose exposure of 1.2 mSv is obtained using these reduced mAs values. It has to be differentiated between virtual colonoscopy for early detection of polyps and CRC in individual patients or as a screening examination of a large population. Virtual colonoscopy as a screening examination necessitates reduction of radiation dose, a high degree of automatisation in 3D reconstructions as well as the assessment of the entire mucosa. High risk patients, whom refuse fibreoptic colonoscopy should undergo virtual colonoscopy. Virtual colonoscopy has a good chance to become an accepted tool for general screening, if efficient dose reduction, complete visualization of the colon mucosa and automatisation of the post processing procedures can be achieved. (orig.) [de
Building a virtual ligand screening pipeline using free software: a survey.
Glaab, Enrico
2016-03-01
Virtual screening, the search for bioactive compounds via computational methods, provides a wide range of opportunities to speed up drug development and reduce the associated risks and costs. While virtual screening is already a standard practice in pharmaceutical companies, its applications in preclinical academic research still remain under-exploited, in spite of an increasing availability of dedicated free databases and software tools. In this survey, an overview of recent developments in this field is presented, focusing on free software and data repositories for screening as alternatives to their commercial counterparts, and outlining how available resources can be interlinked into a comprehensive virtual screening pipeline using typical academic computing facilities. Finally, to facilitate the set-up of corresponding pipelines, a downloadable software system is provided, using platform virtualization to integrate pre-installed screening tools and scripts for reproducible application across different operating systems. © The Author 2015. Published by Oxford University Press.
A virtual test of screening technology based on the AGEIA PhysX
Energy Technology Data Exchange (ETDEWEB)
Ai-min Li; Rui-ling Lv; Chu-sheng Liu [China University of Mining and Technology, Xuzhou (China). School of Mechanical and Electrical Engineering
2008-06-15
The authors have created a virtual test of vibration particle-screening using Autodesk's 3ds Max software, the MAXScript scripting language and the AGEIA PhysX physics processing unit (PPU). The affect of various parameters on screening efficiency were modeled. The parameters included vibration amplitude, frequency and direction. The length and inclination of the vibrating surface were also varied. The virtual experiment is in basic agreement with results predicted from screening theory. This shows that the virtual screener can be used for preliminary investigations and the results used to evaluate screen design. In addition it can help with theoretical research. 11 refs., 7 figs., 7 tabs.
Spherical harmonics coefficients for ligand-based virtual screening of cyclooxygenase inhibitors.
Wang, Quan; Birod, Kerstin; Angioni, Carlo; Grösch, Sabine; Geppert, Tim; Schneider, Petra; Rupp, Matthias; Schneider, Gisbert
2011-01-01
Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort.
Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures
Energy Technology Data Exchange (ETDEWEB)
McLean, Larry R.; Zhang, Ying; Degnen, William; Peppard, Jane; Cabel, Dasha; Zou, Chao; Tsay, Joseph T.; Subramaniam, Arun; Vaz, Roy J.; Li, Yi (Sanofi)
2010-10-28
Amino-benzoic acid derivatives 1-4 were found to be inhibitors for DHODH by virtual screening, biochemical, and X-ray crystallographic studies. X-ray structures showed that 1 and 2 bind to DHODH as predicted by virtual screening, but 3 and 4 were found to be structurally different from the corresponding compounds initially identified by virtual screening.
A virtual screening method for inhibitory peptides of Angiotensin I-converting enzyme.
Wu, Hongxi; Liu, Yalan; Guo, Mingrong; Xie, Jingli; Jiang, XiaMin
2014-09-01
Natural small peptides from foods have been proven to be efficient inhibitors of Angiotensin I-converting enzyme (ACE) for the regulation of blood pressure. The traditional ACE inhibitory peptides screening method is both time consuming and money costing, to the contrary, virtual screening method by computation can break these limitations. We establish a virtual screening method to obtain ACE inhibitory peptides with the help of Libdock module of Discovery Studio 3.5 software. A significant relationship between Libdock score and experimental IC(50) was found, Libdock score = 10.063 log(1/IC(50)) + 68.08 (R(2) = 0.62). The credibility of the relationship was confirmed by testing the coincidence of the estimated log(1/IC(50)) and measured log(1/IC(50)) (IC(50) is 50% inhibitory concentration toward ACE, in μmol/L) of 5 synthetic ACE inhibitory peptides, which was virtual hydrolyzed and screened from a kind of seafood, Phascolosoma esculenta. Accordingly, Libdock method is a valid IC(50) estimation tool and virtual screening method for small ACE inhibitory peptides. © 2014 Institute of Food Technologists®
HPPD: ligand- and target-based virtual screening on a herbicide target.
López-Ramos, Miriam; Perruccio, Francesca
2010-05-24
Hydroxyphenylpyruvate dioxygenase (HPPD) has proven to be a very successful target for the development of herbicides with bleaching properties, and today HPPD inhibitors are well established in the agrochemical market. Syngenta has a long history of HPPD-inhibitor research, and HPPD was chosen as a case study for the validation of diverse ligand- and target-based virtual screening approaches to identify compounds with inhibitory properties. Two-dimensional extended connectivity fingerprints, three-dimensional shape-based tools (ROCS, EON, and Phase-shape) and a pharmacophore approach (Phase) were used as ligand-based methods; Glide and Gold were used as target-based. Both the virtual screening utility and the scaffold-hopping ability of the screening tools were assessed. Particular emphasis was put on the specific pitfalls to take into account for the design of a virtual screening campaign in an agrochemical context, as compared to a pharmaceutical environment.
Virtual screening of cocrystal formers for CL-20
Zhou, Jun-Hong; Chen, Min-Bo; Chen, Wei-Ming; Shi, Liang-Wei; Zhang, Chao-Yang; Li, Hong-Zhen
2014-08-01
According to the structure characteristics of 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20) and the kinetic mechanism of the cocrystal formation, the method of virtual screening CL-20 cocrystal formers by the criterion of the strongest intermolecular site pairing energy (ISPE) was proposed. In this method the strongest ISPE was thought to determine the first step of the cocrystal formation. The prediction results for four sets of common drug molecule cocrystals by this method were compared with those by the total ISPE method from the reference (Musumeci et al., 2011), and the experimental results. This method was then applied to virtually screen the CL-20 cocrystal formers, and the prediction results were compared with the experimental results.
Quantum probability ranking principle for ligand-based virtual screening
Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal
2017-04-01
Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.
Quantum probability ranking principle for ligand-based virtual screening.
Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal
2017-04-01
Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.
Congestion game scheduling for virtual drug screening optimization
Nikitina, Natalia; Ivashko, Evgeny; Tchernykh, Andrei
2018-02-01
In virtual drug screening, the chemical diversity of hits is an important factor, along with their predicted activity. Moreover, interim results are of interest for directing the further research, and their diversity is also desirable. In this paper, we consider a problem of obtaining a diverse set of virtual screening hits in a short time. To this end, we propose a mathematical model of task scheduling for virtual drug screening in high-performance computational systems as a congestion game between computational nodes to find the equilibrium solutions for best balancing the number of interim hits with their chemical diversity. The model considers the heterogeneous environment with workload uncertainty, processing time uncertainty, and limited knowledge about the input dataset structure. We perform computational experiments and evaluate the performance of the developed approach considering organic molecules database GDB-9. The used set of molecules is rich enough to demonstrate the feasibility and practicability of proposed solutions. We compare the algorithm with two known heuristics used in practice and observe that game-based scheduling outperforms them by the hit discovery rate and chemical diversity at earlier steps. Based on these results, we use a social utility metric for assessing the efficiency of our equilibrium solutions and show that they reach greatest values.
Energy Technology Data Exchange (ETDEWEB)
Carrascosa, P; Castiglioni, R; Sanchez, F; Capunay, C; Mazzuco, J; Carrascosa, J [Diagnostico Maipu, Vicente Lopez, Buenos Aires (Argentina)
2000-07-01
The authors presents 46 patients-series with virtual colonoscopy. The findings obtained through virtual colonoscopy were divided into 7 groups: 1) Single polypoid lesion (9 patients); 2) Associated polypoid lesions (11 patients); 3) Tumoral stenosis without synchronic lesion (3 patients); 4) Tumoral stenosis with synchronic lesion (6 patients); 5) Non-tumoral stenosis (4 patients); 6) Normal studies (2 patients); 7) Patients excluded due to wrong preparation (11 patients). We concluded that the virtual colonoscopy is a valid alternative in the screening of the colorectal pathology, showing some advantages when compared to the usual studies, since it is non-invasive, does not require sedation, and allows the staging of the neoplasm. (author)
Prospective Assessment of Virtual Screening Heuristics Derived Using a Novel Fusion Score.
Pertusi, Dante A; O'Donnell, Gregory; Homsher, Michelle F; Solly, Kelli; Patel, Amita; Stahler, Shannon L; Riley, Daniel; Finley, Michael F; Finger, Eleftheria N; Adam, Gregory C; Meng, Juncai; Bell, David J; Zuck, Paul D; Hudak, Edward M; Weber, Michael J; Nothstein, Jennifer E; Locco, Louis; Quinn, Carissa; Amoss, Adam; Squadroni, Brian; Hartnett, Michelle; Heo, Mee Ra; White, Tara; May, S Alex; Boots, Evelyn; Roberts, Kenneth; Cocchiarella, Patrick; Wolicki, Alex; Kreamer, Anthony; Kutchukian, Peter S; Wassermann, Anne Mai; Uebele, Victor N; Glick, Meir; Rusinko, Andrew; Culberson, J Christopher
2017-09-01
High-throughput screening (HTS) is a widespread method in early drug discovery for identifying promising chemical matter that modulates a target or phenotype of interest. Because HTS campaigns involve screening millions of compounds, it is often desirable to initiate screening with a subset of the full collection. Subsequently, virtual screening methods prioritize likely active compounds in the remaining collection in an iterative process. With this approach, orthogonal virtual screening methods are often applied, necessitating the prioritization of hits from different approaches. Here, we introduce a novel method of fusing these prioritizations and benchmark it prospectively on 17 screening campaigns using virtual screening methods in three descriptor spaces. We found that the fusion approach retrieves 15% to 65% more active chemical series than any single machine-learning method and that appropriately weighting contributions of similarity and machine-learning scoring techniques can increase enrichment by 1% to 19%. We also use fusion scoring to evaluate the tradeoff between screening more chemical matter initially in lieu of replicate samples to prevent false-positives and find that the former option leads to the retrieval of more active chemical series. These results represent guidelines that can increase the rate of identification of promising active compounds in future iterative screens.
Virtual Screening of Receptor Sites for Molecularly Imprinted Polymers.
Bates, Ferdia; Cela-Pérez, María Concepción; Karim, Kal; Piletsky, Sergey; López-Vilariño, José Manuel
2016-08-01
Molecularly Imprinted Polymers (MIPs) are highly advantageous in the field of analytical chemistry. However, interference from secondary molecules can also impede capture of a target by a MIP receptor. This greatly complicates the design process and often requires extensive laboratory screening which is time consuming, costly, and creates substantial waste products. Herein, is presented a new technique for screening of "virtually imprinted receptors" for rebinding of the molecular template as well as secondary structures, correlating the virtual predictions with experimentally acquired data in three case studies. This novel technique is particularly applicable to the evaluation and prediction of MIP receptor specificity and efficiency in complex aqueous systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
DOVIS: A Tool for High-throughput Virtual Screening
National Research Council Canada - National Science Library
Jiang, Xiaohui; Kumar, Kamal; Wallqvist, Anders; Reifman, Jaques
2007-01-01
We developed a DOcking-based Virtual Screening (DO DOVIS) pipeline to predict how small molecules may interact with a given protein, so that we can rank a large database of molecules based on their predicted affinities to the protein...
Virtual screening methods as tools for drug lead discovery from large chemical libraries.
Ma, X H; Zhu, F; Liu, X; Shi, Z; Zhang, J X; Yang, S Y; Wei, Y Q; Chen, Y Z
2012-01-01
Virtual screening methods have been developed and explored as useful tools for searching drug lead compounds from chemical libraries, including large libraries that have become publically available. In this review, we discussed the new developments in exploring virtual screening methods for enhanced performance in searching large chemical libraries, their applications in screening libraries of ~ 1 million or more compounds in the last five years, the difficulties in their applications, and the strategies for further improving these methods.
A multi-infrastructure gateway for virtual drug screening
Jaghoori, Mohammad Mahdi; van Altena, Allard J.; Bleijlevens, Boris; Ramezani, Sara; Font, Juan Luis; Olabarriaga, Silvia D.
2015-01-01
In computer-aided drug design, software tools are used to narrow down possible drug candidates, thereby reducing the amount of expensive in vitro research, by a process called virtual screening. This process includes large computations that require advanced computing infrastructure; however, using
GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing
Fang, Ye; Ding, Yun; Feinstein, Wei P.; Koppelman, David M.; Moreno, Juana; Jarrell, Mark; Ramanujam, J.; Brylinski, Michal
2016-01-01
Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249. PMID:27420300
GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.
Directory of Open Access Journals (Sweden)
Ye Fang
Full Text Available Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU. First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.
Kurczab, Rafał; Bojarski, Andrzej J
2017-01-01
The machine learning-based virtual screening of molecular databases is a commonly used approach to identify hits. However, many aspects associated with training predictive models can influence the final performance and, consequently, the number of hits found. Thus, we performed a systematic study of the simultaneous influence of the proportion of negatives to positives in the testing set, the size of screening databases and the type of molecular representations on the effectiveness of classification. The results obtained for eight protein targets, five machine learning algorithms (SMO, Naïve Bayes, Ibk, J48 and Random Forest), two types of molecular fingerprints (MACCS and CDK FP) and eight screening databases with different numbers of molecules confirmed our previous findings that increases in the ratio of negative to positive training instances greatly influenced most of the investigated parameters of the ML methods in simulated virtual screening experiments. However, the performance of screening was shown to also be highly dependent on the molecular library dimension. Generally, with the increasing size of the screened database, the optimal training ratio also increased, and this ratio can be rationalized using the proposed cost-effectiveness threshold approach. To increase the performance of machine learning-based virtual screening, the training set should be constructed in a way that considers the size of the screening database.
Virtual Screening Approaches towards the Discovery of Toll-Like Receptor Modulators
Directory of Open Access Journals (Sweden)
Lucía Pérez-Regidor
2016-09-01
Full Text Available This review aims to summarize the latest efforts performed in the search for novel chemical entities such as Toll-like receptor (TLR modulators by means of virtual screening techniques. This is an emergent research field with only very recent (and successful contributions. Identification of drug-like molecules with potential therapeutic applications for the treatment of a variety of TLR-regulated diseases has attracted considerable interest due to the clinical potential. Additionally, the virtual screening databases and computational tools employed have been overviewed in a descriptive way, widening the scope for researchers interested in the field.
DOVIS 2.0: an efficient and easy to use parallel virtual screening tool based on AutoDock 4.0.
Jiang, Xiaohui; Kumar, Kamal; Hu, Xin; Wallqvist, Anders; Reifman, Jaques
2008-09-08
Small-molecule docking is an important tool in studying receptor-ligand interactions and in identifying potential drug candidates. Previously, we developed a software tool (DOVIS) to perform large-scale virtual screening of small molecules in parallel on Linux clusters, using AutoDock 3.05 as the docking engine. DOVIS enables the seamless screening of millions of compounds on high-performance computing platforms. In this paper, we report significant advances in the software implementation of DOVIS 2.0, including enhanced screening capability, improved file system efficiency, and extended usability. To keep DOVIS up-to-date, we upgraded the software's docking engine to the more accurate AutoDock 4.0 code. We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs. We also implemented an algorithm to output docked ligands in an industry standard format, sd-file format, which can be easily interfaced with other modeling programs. Finally, we constructed a wrapper-script interface to enable automatic rescoring of docked ligands by arbitrarily selected third-party scoring programs. The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability. The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands. The new DOVIS 2.0 package is freely available to the public under the GNU General Public License.
DOVIS 2.0: an efficient and easy to use parallel virtual screening tool based on AutoDock 4.0
Directory of Open Access Journals (Sweden)
Wallqvist Anders
2008-09-01
Full Text Available Abstract Background Small-molecule docking is an important tool in studying receptor-ligand interactions and in identifying potential drug candidates. Previously, we developed a software tool (DOVIS to perform large-scale virtual screening of small molecules in parallel on Linux clusters, using AutoDock 3.05 as the docking engine. DOVIS enables the seamless screening of millions of compounds on high-performance computing platforms. In this paper, we report significant advances in the software implementation of DOVIS 2.0, including enhanced screening capability, improved file system efficiency, and extended usability. Implementation To keep DOVIS up-to-date, we upgraded the software's docking engine to the more accurate AutoDock 4.0 code. We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs. We also implemented an algorithm to output docked ligands in an industry standard format, sd-file format, which can be easily interfaced with other modeling programs. Finally, we constructed a wrapper-script interface to enable automatic rescoring of docked ligands by arbitrarily selected third-party scoring programs. Conclusion The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability. The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands. The new DOVIS 2.0 package is freely available to the public under the GNU General Public License.
Machine learning in virtual screening.
Melville, James L; Burke, Edmund K; Hirst, Jonathan D
2009-05-01
In this review, we highlight recent applications of machine learning to virtual screening, focusing on the use of supervised techniques to train statistical learning algorithms to prioritize databases of molecules as active against a particular protein target. Both ligand-based similarity searching and structure-based docking have benefited from machine learning algorithms, including naïve Bayesian classifiers, support vector machines, neural networks, and decision trees, as well as more traditional regression techniques. Effective application of these methodologies requires an appreciation of data preparation, validation, optimization, and search methodologies, and we also survey developments in these areas.
Directory of Open Access Journals (Sweden)
Abreu Rui MV
2010-10-01
Full Text Available Abstract Background Virtual screening of small molecules using molecular docking has become an important tool in drug discovery. However, large scale virtual screening is time demanding and usually requires dedicated computer clusters. There are a number of software tools that perform virtual screening using AutoDock4 but they require access to dedicated Linux computer clusters. Also no software is available for performing virtual screening with Vina using computer clusters. In this paper we present MOLA, an easy-to-use graphical user interface tool that automates parallel virtual screening using AutoDock4 and/or Vina in bootable non-dedicated computer clusters. Implementation MOLA automates several tasks including: ligand preparation, parallel AutoDock4/Vina jobs distribution and result analysis. When the virtual screening project finishes, an open-office spreadsheet file opens with the ligands ranked by binding energy and distance to the active site. All results files can automatically be recorded on an USB-flash drive or on the hard-disk drive using VirtualBox. MOLA works inside a customized Live CD GNU/Linux operating system, developed by us, that bypass the original operating system installed on the computers used in the cluster. This operating system boots from a CD on the master node and then clusters other computers as slave nodes via ethernet connections. Conclusion MOLA is an ideal virtual screening tool for non-experienced users, with a limited number of multi-platform heterogeneous computers available and no access to dedicated Linux computer clusters. When a virtual screening project finishes, the computers can just be restarted to their original operating system. The originality of MOLA lies on the fact that, any platform-independent computer available can he added to the cluster, without ever using the computer hard-disk drive and without interfering with the installed operating system. With a cluster of 10 processors, and a
Ma, Xiao H; Jia, Jia; Zhu, Feng; Xue, Ying; Li, Ze R; Chen, Yu Z
2009-05-01
Machine learning methods have been explored as ligand-based virtual screening tools for facilitating drug lead discovery. These methods predict compounds of specific pharmacodynamic, pharmacokinetic or toxicological properties based on their structure-derived structural and physicochemical properties. Increasing attention has been directed at these methods because of their capability in predicting compounds of diverse structures and complex structure-activity relationships without requiring the knowledge of target 3D structure. This article reviews current progresses in using machine learning methods for virtual screening of pharmacodynamically active compounds from large compound libraries, and analyzes and compares the reported performances of machine learning tools with those of structure-based and other ligand-based (such as pharmacophore and clustering) virtual screening methods. The feasibility to improve the performance of machine learning methods in screening large libraries is discussed.
Protein-Ligand Empirical Interaction Components for Virtual Screening.
Yan, Yuna; Wang, Weijun; Sun, Zhaoxi; Zhang, John Z H; Ji, Changge
2017-08-28
A major shortcoming of empirical scoring functions is that they often fail to predict binding affinity properly. Removing false positives of docking results is one of the most challenging works in structure-based virtual screening. Postdocking filters, making use of all kinds of experimental structure and activity information, may help in solving the issue. We describe a new method based on detailed protein-ligand interaction decomposition and machine learning. Protein-ligand empirical interaction components (PLEIC) are used as descriptors for support vector machine learning to develop a classification model (PLEIC-SVM) to discriminate false positives from true positives. Experimentally derived activity information is used for model training. An extensive benchmark study on 36 diverse data sets from the DUD-E database has been performed to evaluate the performance of the new method. The results show that the new method performs much better than standard empirical scoring functions in structure-based virtual screening. The trained PLEIC-SVM model is able to capture important interaction patterns between ligand and protein residues for one specific target, which is helpful in discarding false positives in postdocking filtering.
Shave, Steven; Auer, Manfred
2013-12-23
Combinatorial chemical libraries produced on solid support offer fast and cost-effective access to a large number of unique compounds. If such libraries are screened directly on-bead, the speed at which chemical space can be explored by chemists is much greater than that addressable using solution based synthesis and screening methods. Solution based screening has a large supporting body of software such as structure-based virtual screening tools which enable the prediction of protein-ligand complexes. Use of these techniques to predict the protein bound complexes of compounds synthesized on solid support neglects to take into account the conjugation site on the small molecule ligand. This may invalidate predicted binding modes, the linker may be clashing with protein atoms. We present CSBB-ConeExclusion, a methodology and computer program which provides a measure of the applicability of solution dockings to solid support. Output is given in the form of statistics for each docking pose, a unique 2D visualization method which can be used to determine applicability at a glance, and automatically generated PyMol scripts allowing visualization of protein atom incursion into a defined exclusion volume. CSBB-ConeExclusion is then exemplarically used to determine the optimum attachment point for a purine library targeting cyclin-dependent kinase 2 CDK2.
Identification of VDR Antagonists among Nuclear Receptor Ligands Using Virtual Screening
Directory of Open Access Journals (Sweden)
Kelly Teske
2014-04-01
Full Text Available Herein, we described the development of two virtual screens to identify new vitamin D receptor (VDR antagonists among nuclear receptor (NR ligands. Therefore, a database of 14330 nuclear receptor ligands and their NR affinities was assembled using the online available “Binding Database.” Two different virtual screens were carried out in conjunction with a reported VDR crystal structure applying a stringent and less stringent pharmacophore model to filter docked NR ligand conformations. The pharmacophore models were based on the spatial orientation of the hydroxyl functionalities of VDR's natural ligands 1,25(OH2D3 and 25(OH2D3. The first virtual screen identified 32 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. All but nordihydroguaiaretic acid (NDGA are VDR ligands, which inhibited the interaction between VDR and coactivator peptide SRC2-3 with an IC50 value of 15.8 μM. The second screen identified 162 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. More than half of these ligands were developed to bind VDR followed by ERα/β ligands (26%, TRα/β ligands (7%, and LxRα/β ligands (7%. The binding between VDR and ERα ligand H6036 as well as TRα/β ligand triiodothyronine and a homoserine analog thereof was confirmed by fluorescence polarization.
Performance of machine learning methods for ligand-based virtual screening.
Plewczynski, Dariusz; Spieser, Stéphane A H; Koch, Uwe
2009-05-01
Computational screening of compound databases has become increasingly popular in pharmaceutical research. This review focuses on the evaluation of ligand-based virtual screening using active compounds as templates in the context of drug discovery. Ligand-based screening techniques are based on comparative molecular similarity analysis of compounds with known and unknown activity. We provide an overview of publications that have evaluated different machine learning methods, such as support vector machines, decision trees, ensemble methods such as boosting, bagging and random forests, clustering methods, neuronal networks, naïve Bayesian, data fusion methods and others.
Computed Tomographic Virtual Colonoscopy to Screen for Colorectal Neoplasia in asymptomatic adults
International Nuclear Information System (INIS)
Pickhardt, Perry J.; Choi, J Richard; Hwang, Inku and others
2004-01-01
We evaluated the performance characteristics of computed tomographic (CT) virtual colonospy for the detection of colorectal neoplasia in an average-risk screening population. A total of 1233 symptomatic adults (mean age, 57.8 years) underwent same-day virtual and optical colonoscopy. Radiologists used the three-dimensional endoluminal display for the initial detection of polyps on CT virtual colonoscopy. For the initial examination of each colonic segment, the colonoscopists were unaware of the findings on virtual colonoscopy, which were revealed to them before any subsequent reexamination. The sensitivity and specificity of virtual colonoscopy and the sensitivity of optical colonoscopy were calculated with the use of the findings of the final, unblinded optical colonoscopy as the reference standard. The sensitivity of virtual colonoscopy for adenomatous polyps was 93.8 percent for polyps at least 10 mm in diameter, 93.9 percent for polyps at least 8 mm in diameter, and 88.7 percent for polyps at least 6 mm in diameter. The sensitivity of optical colonoscopy for adenomatous polyps was 87.5 percent, 91.5 percent, and 92.3 percent for the three sizes of polyps, respectively. The specificity of virtual colonoscopy for adenomatous polyps was 96.0 percent for polyps at least 10 mm in diameter, 92.2 percent for polyps at least 8 mm in diameter, and 79.6 percent for polyps at least 6 mm in diameter.Two polyps were malignant; both were detected on virtual colonoscopy, and one of them was missed on optical colonoscopy before the results on virtual colonoscopy were revealed. CT virtual colonoscopy with the use of a three-dimensional approach is an accurate screening method for the detection of colorectal neoplasia in symptomatic average-risk adults and compares favorably with optical colonoscopy in terms of the detection of clinically relevant lesions
Virtual Machine Logbook - Enabling virtualization for ATLAS
International Nuclear Information System (INIS)
Yao Yushu; Calafiura, Paolo; Leggett, Charles; Poffet, Julien; Cavalli, Andrea; Frederic, Bapst
2010-01-01
ATLAS software has been developed mostly on CERN linux cluster lxplus or on similar facilities at the experiment Tier 1 centers. The fast rise of virtualization technology has the potential to change this model, turning every laptop or desktop into an ATLAS analysis platform. In the context of the CernVM project we are developing a suite of tools and CernVM plug-in extensions to promote the use of virtualization for ATLAS analysis and software development. The Virtual Machine Logbook (VML), in particular, is an application to organize work of physicists on multiple projects, logging their progress, and speeding up ''context switches'' from one project to another. An important feature of VML is the ability to share with a single 'click' the status of a given project with other colleagues. VML builds upon the save and restore capabilities of mainstream virtualization software like VMware, and provides a technology-independent client interface to them. A lot of emphasis in the design and implementation has gone into optimizing the save and restore process to makepractical to store many VML entries on a typical laptop disk or to share a VML entry over the network. At the same time, taking advantage of CernVM's plugin capabilities, we are extending the CernVM platform to help increase the usability of ATLAS software. For example, we added the ability to start the ATLAS event display on any computer running CernVM simply by clicking a button in a web browser. We want to integrate seamlessly VML with CernVM unique file system design to distribute efficiently ATLAS software on every physicist computer. The CernVM File System (CVMFS) download files on-demand via HTTP, and cache it locally for future use. This reduces by one order of magnitude the download sizes, making practical for a developer to work with multiple software releases on a virtual machine.
DEFF Research Database (Denmark)
Askjær, Sune; Langgård, Morten
2008-01-01
The criterion of success for the initial stages of a ligand-based drug-discovery project is dual. First, a set of suitable lead compounds has to be identified. Second, a level of a preliminary structure-activity relationship (SAR) of the identified ligands has to be established in order to guide ...... by the protein-binding site known from X-ray complexes. The result of this analysis assists in explaining the efficiency of 2D pharmacophore fingerprints as descriptors in virtual screening....... the lead optimization toward a final drug candidate. This paper presents a combined approach to solving these two problems of ligand-based virtual screening and elucidation of SAR based on interplay between pharmacophore fingerprints and interpretation of PLS-discriminant analysis (PLS-DA) models....... The virtual screening capability of the PLS-DA method is compared to group fusion maximum similarity searching in a test using four graph-based pharmacophore fingerprints over a range of 10 diverse targets. The PLS-DA method was generally found to do better than the Smax method. The GpiDAPH3 and PCH...
Role of Chemical Reactivity and Transition State Modeling for Virtual Screening.
Karthikeyan, Muthukumarasamy; Vyas, Renu; Tambe, Sanjeev S; Radhamohan, Deepthi; Kulkarni, Bhaskar D
2015-01-01
Every drug discovery research program involves synthesis of a novel and potential drug molecule utilizing atom efficient, economical and environment friendly synthetic strategies. The current work focuses on the role of the reactivity based fingerprints of compounds as filters for virtual screening using a tool ChemScore. A reactant-like (RLS) and a product- like (PLS) score can be predicted for a given compound using the binary fingerprints derived from the numerous known organic reactions which capture the molecule-molecule interactions in the form of addition, substitution, rearrangement, elimination and isomerization reactions. The reaction fingerprints were applied to large databases in biology and chemistry, namely ChEMBL, KEGG, HMDB, DSSTox, and the Drug Bank database. A large network of 1113 synthetic reactions was constructed to visualize and ascertain the reactant product mappings in the chemical reaction space. The cumulative reaction fingerprints were computed for 4000 molecules belonging to 29 therapeutic classes of compounds, and these were found capable of discriminating between the cognition disorder related and anti-allergy compounds with reasonable accuracy of 75% and AUC 0.8. In this study, the transition state based fingerprints were also developed and used effectively for virtual screening in drug related databases. The methodology presented here provides an efficient handle for the rapid scoring of molecular libraries for virtual screening.
Virtual screening of electron acceptor materials for organic photovoltaic applications
International Nuclear Information System (INIS)
D Halls, Mathew; Giesen, David J; Goldberg, Alexander; Djurovich, Peter J; Sommer, Jonathan; McAnally, Eric; Thompson, Mark E
2013-01-01
Virtual screening involves the generation of structure libraries, automated analysis to predict properties related to application performance and subsequent screening to identify lead systems and estimate critical structure–property limits across a targeted chemical design space. This approach holds great promise for informing experimental discovery and development efforts for next-generation materials, such as organic semiconductors. In this work, the virtual screening approach is illustrated for nitrogen-substituted pentacene molecules to identify systems for development as electron acceptor materials for use in organic photovoltaic (OPV) devices. A structure library of tetra-azapentacenes (TAPs) was generated by substituting four nitrogens for CH at 12 sites on the pentacene molecular framework. Molecular properties (e.g. E LUMO , E g and μ) were computed for each candidate structure using hybrid DFT at the B3LYP/6-311G** level of theory. The resulting TAPs library was then analyzed with respect to intrinsic properties associated with OPV acceptor performance. Marcus reorganization energies for charge transport for the most favorable TAP candidates were then calculated to further determine suitability as OPV electron acceptors. The synthesis, characterization and OPV device testing of TAP materials is underway, guided by these results. (paper)
Virtual drug screen schema based on multiview similarity integration and ranking aggregation.
Kang, Hong; Sheng, Zhen; Zhu, Ruixin; Huang, Qi; Liu, Qi; Cao, Zhiwei
2012-03-26
The current drug virtual screen (VS) methods mainly include two categories. i.e., ligand/target structure-based virtual screen and that, utilizing protein-ligand interaction fingerprint information based on the large number of complex structures. Since the former one focuses on the one-side information while the later one focuses on the whole complex structure, they are thus complementary and can be boosted by each other. However, a common problem faced here is how to present a comprehensive understanding and evaluation of the various virtual screen results derived from various VS methods. Furthermore, there is still an urgent need for developing an efficient approach to fully integrate various VS methods from a comprehensive multiview perspective. In this study, our virtual screen schema based on multiview similarity integration and ranking aggregation was tested comprehensively with statistical evaluations, providing several novel and useful clues on how to perform drug VS from multiple heterogeneous data sources. (1) 18 complex structures of HIV-1 protease with ligands from the PDB were curated as a test data set and the VS was performed with five different drug representations. Ritonavir ( 1HXW ) was selected as the query in VS and the weighted ranks of the query results were aggregated from multiple views through four similarity integration approaches. (2) Further, one of the ranking aggregation methods was used to integrate the similarity ranks calculated by gene ontology (GO) fingerprint and structural fingerprint on the data set from connectivity map, and two typical HDAC and HSP90 inhibitors were chosen as the queries. The results show that rank aggregation can enhance the result of similarity searching in VS when two or more descriptions are involved and provide a more reasonable similarity rank result. Our study shows that integrated VS based on multiple data fusion can achieve a remarkable better performance compared to that from individual ones and
Screening and dotting virtual slides: A new challenge for cytotechnologists
Directory of Open Access Journals (Sweden)
Walid E Khalbuss
2013-01-01
Full Text Available Digital images are increasingly being used in cytopathology. Whole-slide imaging (WSI is a digital imaging modality that uses computerized technology to scan and convert entire cytology glass slides into digital images that can be viewed on a digital display using the image viewer software. Digital image acquisition of cytology glass slides has improved significantly over the years due to the use of liquid-based preparations and advances in WSI scanning technology such as automatic multipoint pre-scan focus technology or z-stack scanning technology. Screening cytotechnologists are responsible for every cell that is present on an imaged slide. One of the challenges users have to overcome is to establish a technique to review systematically the entire imaged slide and to dot selected abnormal or significant findings. The scope of this article is to review the current user interface technology available for virtual slide navigation when screening digital slides in cytology. WSI scanner vendors provide tools, built into the image viewer software that allow for a more systematic navigation of the virtual slides, such as auto-panning, keyboard-controlled slide navigation and track map. Annotation tools can improve communication between the screener and the final reviewer or can be used for education. The tracking functionality allows recording of the WSI navigation process and provides a mechanism for confirmation of slide coverage by the screening cytotechnologist as well as a useful tool for quality assurance. As the WSI technology matures, additional features and tools to support navigation of a cytology virtual slide are anticipated.
Virtual high screening throughput and design of 14α-lanosterol ...
African Journals Online (AJOL)
STORAGESEVER
2009-07-06
Jul 6, 2009 ... Virtual high screening throughput and design of. 14α-lanosterol demethylase inhibitors against. Mycobacterium tuberculosis. Hildebert B. Maurice1*, Esther Tuarira1 and Kennedy Mwambete2. 1School of Pharmaceutical Sciences, Institute of Allied Health Sciences, Muhimbili University of Health and.
Joslin, John; Gilligan, James; Anderson, Paul; Garcia, Catherine; Sharif, Orzala; Hampton, Janice; Cohen, Steven; King, Miranda; Zhou, Bin; Jiang, Shumei; Trussell, Christopher; Dunn, Robert; Fathman, John W; Snead, Jennifer L; Boitano, Anthony E; Nguyen, Tommy; Conner, Michael; Cooke, Mike; Harris, Jennifer; Ainscow, Ed; Zhou, Yingyao; Shaw, Chris; Sipes, Dan; Mainquist, James; Lesley, Scott
2018-05-01
The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting. Advanced automation and high-content imaging have enabled many complex assays, but these are still relatively slow and low throughput. To address this limitation, we have developed an automated workflow that is dedicated to processing complex phenotypic assays for flow cytometry. The system can achieve a throughput of 50,000 wells per day, resulting in a fully automated platform that enables robust phenotypic drug discovery. Over the past 5 years, this screening system has been used for a variety of drug discovery programs, across many disease areas, with many molecules advancing quickly into preclinical development and into the clinic. This report will highlight a diversity of approaches that automated flow cytometry has enabled for phenotypic drug discovery.
Interactive screen experiments-innovative virtual laboratories for distance learners
International Nuclear Information System (INIS)
Hatherly, P A; Jordan, S E; Cayless, A
2009-01-01
The desirability and value of laboratory work for physics students is a well-established principle and issues arise where students are inherently remote from their host institution, as is the case for the UK's Open University. In this paper, we present developments from the Physics Innovations Centre for Excellence in Teaching and Learning (piCETL) in the production and technology of the virtual laboratory resources, interactive screen experiments, and the benefits and drawbacks of such resources. We also explore the motivations behind current implementation of interactive screen experiments and examine evaluation strategies and outcomes through a series of case studies
A cross docking pipeline for improving pose prediction and virtual screening performance
Kumar, Ashutosh; Zhang, Kam Y. J.
2018-01-01
Pose prediction and virtual screening performance of a molecular docking method depend on the choice of protein structures used for docking. Multiple structures for a target protein are often used to take into account the receptor flexibility and problems associated with a single receptor structure. However, the use of multiple receptor structures is computationally expensive when docking a large library of small molecules. Here, we propose a new cross-docking pipeline suitable to dock a large library of molecules while taking advantage of multiple target protein structures. Our method involves the selection of a suitable receptor for each ligand in a screening library utilizing ligand 3D shape similarity with crystallographic ligands. We have prospectively evaluated our method in D3R Grand Challenge 2 and demonstrated that our cross-docking pipeline can achieve similar or better performance than using either single or multiple-receptor structures. Moreover, our method displayed not only decent pose prediction performance but also better virtual screening performance over several other methods.
[Virtual reality in neurosurgery].
Tronnier, V M; Staubert, A; Bonsanto, M M; Wirtz, C R; Kunze, S
2000-03-01
Virtual reality enables users to immerse themselves in a virtual three-dimensional world and to interact in this world. The simulation is different from the kind in computer games, in which the viewer is active but acts in a nonrealistic world, or on the TV screen, where we are passively driven in an active world. In virtual reality elements look realistic, they change their characteristics and have almost real-world unpredictability. Virtual reality is not only implemented in gambling dens and the entertainment industry but also in manufacturing processes (cars, furniture etc.), military applications and medicine. Especially the last two areas are strongly correlated, because telemedicine or telesurgery was originated for military reasons to operate on war victims from a secure distance or to perform surgery on astronauts in an orbiting space station. In medicine and especially neurosurgery virtual-reality methods are used for education, surgical planning and simulation on a virtual patient.
How to benchmark methods for structure-based virtual screening of large compound libraries.
Christofferson, Andrew J; Huang, Niu
2012-01-01
Structure-based virtual screening is a useful computational technique for ligand discovery. To systematically evaluate different docking approaches, it is important to have a consistent benchmarking protocol that is both relevant and unbiased. Here, we describe the designing of a benchmarking data set for docking screen assessment, a standard docking screening process, and the analysis and presentation of the enrichment of annotated ligands among a background decoy database.
Application of Shape Similarity in Pose Selection and Virtual Screening in CSARdock2014 Exercise.
Kumar, Ashutosh; Zhang, Kam Y J
2016-06-27
To evaluate the applicability of shape similarity in docking-based pose selection and virtual screening, we participated in the CSARdock2014 benchmark exercise for identifying the correct docking pose of inhibitors targeting factor XA, spleen tyrosine kinase, and tRNA methyltransferase. This exercise provides a valuable opportunity for researchers to test their docking programs, methods, and protocols in a blind testing environment. In the CSARdock2014 benchmark exercise, we have implemented an approach that uses ligand 3D shape similarity to facilitate docking-based pose selection and virtual screening. We showed here that ligand 3D shape similarity between bound poses could be used to identify the native-like pose from an ensemble of docking-generated poses. Our method correctly identified the native pose as the top-ranking pose for 73% of test cases in a blind testing environment. Moreover, the pose selection results also revealed an excellent correlation between ligand 3D shape similarity scores and RMSD to X-ray crystal structure ligand. In the virtual screening exercise, the average RMSD for our pose prediction was found to be 1.02 Å, and it was one of the top performances achieved in CSARdock2014 benchmark exercise. Furthermore, the inclusion of shape similarity improved virtual screening performance of docking-based scoring and ranking. The coefficient of determination (r(2)) between experimental activities and docking scores for 276 spleen tyrosine kinase inhibitors was found to be 0.365 but reached 0.614 when the ligand 3D shape similarity was included.
Enabling scientific workflows in virtual reality
Kreylos, O.; Bawden, G.; Bernardin, T.; Billen, M.I.; Cowgill, E.S.; Gold, R.D.; Hamann, B.; Jadamec, M.; Kellogg, L.H.; Staadt, O.G.; Sumner, D.Y.
2006-01-01
To advance research and improve the scientific return on data collection and interpretation efforts in the geosciences, we have developed methods of interactive visualization, with a special focus on immersive virtual reality (VR) environments. Earth sciences employ a strongly visual approach to the measurement and analysis of geologic data due to the spatial and temporal scales over which such data ranges, As observations and simulations increase in size and complexity, the Earth sciences are challenged to manage and interpret increasing amounts of data. Reaping the full intellectual benefits of immersive VR requires us to tailor exploratory approaches to scientific problems. These applications build on the visualization method's strengths, using both 3D perception and interaction with data and models, to take advantage of the skills and training of the geological scientists exploring their data in the VR environment. This interactive approach has enabled us to develop a suite of tools that are adaptable to a range of problems in the geosciences and beyond. Copyright ?? 2008 by the Association for Computing Machinery, Inc.
Zhang, Li; Ai, Hai-Xin; Li, Shi-Meng; Qi, Meng-Yuan; Zhao, Jian; Zhao, Qi; Liu, Hong-Sheng
2017-10-10
In recent years, an epidemic of the highly pathogenic avian influenza H7N9 virus has persisted in China, with a high mortality rate. To develop novel anti-influenza therapies, we have constructed a machine-learning-based scoring function (RF-NA-Score) for the effective virtual screening of lead compounds targeting the viral neuraminidase (NA) protein. RF-NA-Score is more accurate than RF-Score, with a root-mean-square error of 1.46, Pearson's correlation coefficient of 0.707, and Spearman's rank correlation coefficient of 0.707 in a 5-fold cross-validation study. The performance of RF-NA-Score in a docking-based virtual screening of NA inhibitors was evaluated with a dataset containing 281 NA inhibitors and 322 noninhibitors. Compared with other docking-rescoring virtual screening strategies, rescoring with RF-NA-Score significantly improved the efficiency of virtual screening, and a strategy that averaged the scores given by RF-NA-Score, based on the binding conformations predicted with AutoDock, AutoDock Vina, and LeDock, was shown to be the best strategy. This strategy was then applied to the virtual screening of NA inhibitors in the SPECS database. The 100 selected compounds were tested in an in vitro H7N9 NA inhibition assay, and two compounds with novel scaffolds showed moderate inhibitory activities. These results indicate that RF-NA-Score improves the efficiency of virtual screening for NA inhibitors, and can be used successfully to identify new NA inhibitor scaffolds. Scoring functions specific for other drug targets could also be established with the same method.
Directory of Open Access Journals (Sweden)
Cristina Portalés
2017-06-01
Full Text Available The geometric calibration of projectors is a demanding task, particularly for the industry of virtual reality simulators. Different methods have been developed during the last decades to retrieve the intrinsic and extrinsic parameters of projectors, most of them being based on planar homographies and some requiring an extended calibration process. The aim of our research work is to design a fast and user-friendly method to provide multi-projector calibration on analytically defined screens, where a sample is shown for a virtual reality Formula 1 simulator that has a cylindrical screen. The proposed method results from the combination of surveying, photogrammetry and image processing approaches, and has been designed by considering the spatial restrictions of virtual reality simulators. The method has been validated from a mathematical point of view, and the complete system—which is currently installed in a shopping mall in Spain—has been tested by different users.
Comparative analysis of pharmacophore screening tools.
Sanders, M.P.A.; Barbosa, A.J.; Zarzycka, B.; Nicolaes, G.A.; Klomp, J.P.G.; Vlieg, J. de; Rio, A. Del
2012-01-01
The pharmacophore concept is of central importance in computer-aided drug design (CADD) mainly because of its successful application in medicinal chemistry and, in particular, high-throughput virtual screening (HTVS). The simplicity of the pharmacophore definition enables the complexity of molecular
Enabling Virtual Sensing as a Service
Directory of Open Access Journals (Sweden)
Yang Li
2016-03-01
Full Text Available In many situations, placing a physical sensor in the ideal position in or on the human body to acquire sensing data is incredibly difficult. Virtual sensors, in contrast to physical sensors, can provide indirect measurements by making use of other available sensor data. In this paper, we demonstrate a virtual sensing application developed as a service on top of a cloud-based health sensor data management platform called Wiki-Health. The proposed application “implants” virtual sensors in the human body by integrating environmental, geographic and personal sensor data with physiological models to compute temperature estimations of various parts of the body. The feasibility of the proposed virtual sensing service is supported by a case study. The ability to share computational models relevant to do calculations on measured data on the go is also discussed.
Teaching Basic Field Skills Using Screen-Based Virtual Reality Landscapes
Houghton, J.; Robinson, A.; Gordon, C.; Lloyd, G. E. E.; Morgan, D. J.
2016-12-01
We are using screen-based virtual reality landscapes, created using the Unity 3D game engine, to augment the training geoscience students receive in preparing for fieldwork. Students explore these landscapes as they would real ones, interacting with virtual outcrops to collect data, determine location, and map the geology. Skills for conducting field geological surveys - collecting, plotting and interpreting data; time management and decision making - are introduced interactively and intuitively. As with real landscapes, the virtual landscapes are open-ended terrains with embedded data. This means the game does not structure student interaction with the information as it is through experience the student learns the best methods to work successfully and efficiently. These virtual landscapes are not replacements for geological fieldwork rather virtual spaces between classroom and field in which to train and reinforcement essential skills. Importantly, these virtual landscapes offer accessible parallel provision for students unable to visit, or fully partake in visiting, the field. The project has received positive feedback from both staff and students. Results show students find it easier to focus on learning these basic field skills in a classroom, rather than field setting, and make the same mistakes as when learning in the field, validating the realistic nature of the virtual experience and providing opportunity to learn from these mistakes. The approach also saves time, and therefore resources, in the field as basic skills are already embedded. 70% of students report increased confidence with how to map boundaries and 80% have found the virtual training a useful experience. We are also developing landscapes based on real places with 3D photogrammetric outcrops, and a virtual urban landscape in which Engineering Geology students can conduct a site investigation. This project is a collaboration between the University of Leeds and Leeds College of Art, UK, and all
Novel Data Mining Methods for Virtual Screening of Biological Active Chemical Compounds
Soufan, Othman
2016-01-01
compounds as candidate drugs for the treatment. Computational resources have been playing a significant role in this part through a step known as virtual screening. From a data mining perspective, availability of rich data resources is key in training
Enabling Research Network Connectivity to Clouds with Virtual Router Technology
Seuster, R.; Casteels, K.; Leavett-Brown, CR; Paterson, M.; Sobie, RJ
2017-10-01
The use of opportunistic cloud resources by HEP experiments has significantly increased over the past few years. Clouds that are owned or managed by the HEP community are connected to the LHCONE network or the research network with global access to HEP computing resources. Private clouds, such as those supported by non-HEP research funds are generally connected to the international research network; however, commercial clouds are either not connected to the research network or only connect to research sites within their national boundaries. Since research network connectivity is a requirement for HEP applications, we need to find a solution that provides a high-speed connection. We are studying a solution with a virtual router that will address the use case when a commercial cloud has research network connectivity in a limited region. In this situation, we host a virtual router in our HEP site and require that all traffic from the commercial site transit through the virtual router. Although this may increase the network path and also the load on the HEP site, it is a workable solution that would enable the use of the remote cloud for low I/O applications. We are exploring some simple open-source solutions. In this paper, we present the results of our studies and how it will benefit our use of private and public clouds for HEP computing.
Library fingerprints: a novel approach to the screening of virtual libraries.
Klon, Anthony E; Diller, David J
2007-01-01
We propose a novel method to prioritize libraries for combinatorial synthesis and high-throughput screening that assesses the viability of a particular library on the basis of the aggregate physical-chemical properties of the compounds using a naïve Bayesian classifier. This approach prioritizes collections of related compounds according to the aggregate values of their physical-chemical parameters in contrast to single-compound screening. The method is also shown to be useful in screening existing noncombinatorial libraries when the compounds in these libraries have been previously clustered according to their molecular graphs. We show that the method used here is comparable or superior to the single-compound virtual screening of combinatorial libraries and noncombinatorial libraries and is superior to the pairwise Tanimoto similarity searching of a collection of combinatorial libraries.
Role of Open Source Tools and Resources in Virtual Screening for Drug Discovery.
Karthikeyan, Muthukumarasamy; Vyas, Renu
2015-01-01
Advancement in chemoinformatics research in parallel with availability of high performance computing platform has made handling of large scale multi-dimensional scientific data for high throughput drug discovery easier. In this study we have explored publicly available molecular databases with the help of open-source based integrated in-house molecular informatics tools for virtual screening. The virtual screening literature for past decade has been extensively investigated and thoroughly analyzed to reveal interesting patterns with respect to the drug, target, scaffold and disease space. The review also focuses on the integrated chemoinformatics tools that are capable of harvesting chemical data from textual literature information and transform them into truly computable chemical structures, identification of unique fragments and scaffolds from a class of compounds, automatic generation of focused virtual libraries, computation of molecular descriptors for structure-activity relationship studies, application of conventional filters used in lead discovery along with in-house developed exhaustive PTC (Pharmacophore, Toxicophores and Chemophores) filters and machine learning tools for the design of potential disease specific inhibitors. A case study on kinase inhibitors is provided as an example.
Statistical Analysis of EGFR Structures’ Performance in Virtual Screening
Li, Yan; Li, Xiang; Dong, Zigang
2015-01-01
In this work the ability of EGFR structures to distinguish true inhibitors from decoys in docking and MM-PBSA is assessed by statistical procedures. The docking performance depends critically on the receptor conformation and bound state. The enrichment of known inhibitors is well correlated with the difference between EGFR structures rather than the bound-ligand property. The optimal structures for virtual screening can be selected based purely on the complex information. And the mixed combination of distinct EGFR conformations is recommended for ensemble docking. In MM-PBSA, a variety of EGFR structures have identically good performance in the scoring and ranking of known inhibitors, indicating that the choice of the receptor structure has little effect on the screening. PMID:26476847
Assessing the utility and limitations of high throughput virtual screening
Directory of Open Access Journals (Sweden)
Paul Daniel Phillips
2016-05-01
Full Text Available Due to low cost, speed, and unmatched ability to explore large numbers of compounds, high throughput virtual screening and molecular docking engines have become widely utilized by computational scientists. It is generally accepted that docking engines, such as AutoDock, produce reliable qualitative results for ligand-macromolecular receptor binding, and molecular docking results are commonly reported in literature in the absence of complementary wet lab experimental data. In this investigation, three variants of the sixteen amino acid peptide, α-conotoxin MII, were docked to a homology model of the a3β2-nicotinic acetylcholine receptor. DockoMatic version 2.0 was used to perform a virtual screen of each peptide ligand to the receptor for ten docking trials consisting of 100 AutoDock cycles per trial. The results were analyzed for both variation in the calculated binding energy obtained from AutoDock, and the orientation of bound peptide within the receptor. The results show that, while no clear correlation exists between consistent ligand binding pose and the calculated binding energy, AutoDock is able to determine a consistent positioning of bound peptide in the majority of trials when at least ten trials were evaluated.
Enabling virtual communities: Gulliver and Aveiro
Nijholt, Antinus; Faisal, K.; Sarfraz, M.
2002-01-01
In this paper we discuss two of our projects on virtual realities. First there is the virtual reality project Gulliver. This project is part of a more comprehensive project conceived by two artists, Matjaž Štuk and Alena Hudcovicová, called “Gulliver’s Museum of Living Art��?. Our part of the
Identification by shape-based virtual screening and evaluation of new tyrosinase inhibitors
Directory of Open Access Journals (Sweden)
Qi Li
2018-01-01
Full Text Available Targeting tyrosinase is considered to be an effective way to control the production of melanin. Tyrosinase inhibitor is anticipated to provide new therapy to prevent skin pigmentation, melanoma and neurodegenerative diseases. Herein, we report our results in identifying new tyrosinase inhibitors. The shape-based virtual screening was performed to discover new tyrosinase inhibitors. Thirteen potential hits derived from virtual screening were tested by biological determinations. Compound 5186-0429 exhibited the most potent inhibitory activity. It dose-dependently inhibited the activity of tyrosinase, with the IC50 values 6.2 ± 2.0 µM and 10.3 ± 5.4 µM on tyrosine and L-Dopa formation, respectively. The kinetic study of 5186-0429 demonstrated that this compound acted as a competitive inhibitor. We believe the discoveries here could serve as a good starting point for further design of potent tyrosinase inhibitor.
Fleming, Michael; Olsen, Dale; Stathes, Hilary; Boteler, Laura; Grossberg, Paul; Pfeifer, Judie; Schiro, Stephanie; Banning, Jane; Skochelak, Susan
2009-01-01
Educating physicians and other health care professionals about the identification and treatment of patients who drink more than recommended limits is an ongoing challenge. An educational randomized controlled trial was conducted to test the ability of a stand-alone training simulation to improve the clinical skills of health care professionals in alcohol screening and intervention. The "virtual reality simulation" combined video, voice recognition, and nonbranching logic to create an interactive environment that allowed trainees to encounter complex social cues and realistic interpersonal exchanges. The simulation included 707 questions and statements and 1207 simulated patient responses. A sample of 102 health care professionals (10 physicians; 30 physician assistants or nurse practitioners; 36 medical students; 26 pharmacy, physican assistant, or nurse practitioner students) were randomly assigned to a no training group (n = 51) or a computer-based virtual reality intervention (n = 51). Professionals in both groups had similar pretest standardized patient alcohol screening skill scores: 53.2 (experimental) vs 54.4 (controls), 52.2 vs 53.7 alcohol brief intervention skills, and 42.9 vs 43.5 alcohol referral skills. After repeated practice with the simulation there were significant increases in the scores of the experimental group at 6 months after randomization compared with the control group for the screening (67.7 vs 58.1; P virtual reality simulation to demonstrate an increase in the alcohol screening and brief intervention skills of health care professionals.
Duffy, Fergal J; Verniere, Mélanie; Devocelle, Marc; Bernard, Elise; Shields, Denis C; Chubb, Anthony J
2011-04-25
We introduce CycloPs, software for the generation of virtual libraries of constrained peptides including natural and nonnatural commercially available amino acids. The software is written in the cross-platform Python programming language, and features include generating virtual libraries in one-dimensional SMILES and three-dimensional SDF formats, suitable for virtual screening. The stand-alone software is capable of filtering the virtual libraries using empirical measurements, including peptide synthesizability by standard peptide synthesis techniques, stability, and the druglike properties of the peptide. The software and accompanying Web interface is designed to enable the rapid generation of large, structurally diverse, synthesizable virtual libraries of constrained peptides quickly and conveniently, for use in virtual screening experiments. The stand-alone software, and the Web interface for evaluating these empirical properties of a single peptide, are available at http://bioware.ucd.ie .
Zary, Nabil; Hege, Inga; Heid, Jörn; Woodham, Luke; Donkers, Jeroen; Kononowicz, Andrzej A
2009-01-01
Virtual Patients (VPs) have successfully been integrated into medical and healthcare curricula for a number of years. Lack of time and resources is a frequently reported problem encountered when developing VPs for teaching and learning. Consequently there is a need for cross-institutional repositories of VPs. The aims of the study were two-fold: to enable interoperability between virtual patient systems and to investigate if (and how) an application profile is implemented in four different types of VP systems. This European collaborative implementation of a blend of several specifications (Medbiquitous VP XML, Medbiquitous Healthcare LOM, and SCORM) is innovative and the study has shown a variation in how the application profile could be implemented.
Enabling Diverse Software Stacks on Supercomputers using High Performance Virtual Clusters.
Energy Technology Data Exchange (ETDEWEB)
Younge, Andrew J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Pedretti, Kevin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Grant, Ryan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Brightwell, Ron [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
2017-05-01
While large-scale simulations have been the hallmark of the High Performance Computing (HPC) community for decades, Large Scale Data Analytics (LSDA) workloads are gaining attention within the scientific community not only as a processing component to large HPC simulations, but also as standalone scientific tools for knowledge discovery. With the path towards Exascale, new HPC runtime systems are also emerging in a way that differs from classical distributed com- puting models. However, system software for such capabilities on the latest extreme-scale DOE supercomputing needs to be enhanced to more appropriately support these types of emerging soft- ware ecosystems. In this paper, we propose the use of Virtual Clusters on advanced supercomputing resources to enable systems to support not only HPC workloads, but also emerging big data stacks. Specifi- cally, we have deployed the KVM hypervisor within Cray's Compute Node Linux on a XC-series supercomputer testbed. We also use libvirt and QEMU to manage and provision VMs directly on compute nodes, leveraging Ethernet-over-Aries network emulation. To our knowledge, this is the first known use of KVM on a true MPP supercomputer. We investigate the overhead our solution using HPC benchmarks, both evaluating single-node performance as well as weak scaling of a 32-node virtual cluster. Overall, we find single node performance of our solution using KVM on a Cray is very efficient with near-native performance. However overhead increases by up to 20% as virtual cluster size increases, due to limitations of the Ethernet-over-Aries bridged network. Furthermore, we deploy Apache Spark with large data analysis workloads in a Virtual Cluster, ef- fectively demonstrating how diverse software ecosystems can be supported by High Performance Virtual Clusters.
Heikamp, Kathrin; Bajorath, Jürgen
2013-07-22
The choice of negative training data for machine learning is a little explored issue in chemoinformatics. In this study, the influence of alternative sets of negative training data and different background databases on support vector machine (SVM) modeling and virtual screening has been investigated. Target-directed SVM models have been derived on the basis of differently composed training sets containing confirmed inactive molecules or randomly selected database compounds as negative training instances. These models were then applied to search background databases consisting of biological screening data or randomly assembled compounds for available hits. Negative training data were found to systematically influence compound recall in virtual screening. In addition, different background databases had a strong influence on the search results. Our findings also indicated that typical benchmark settings lead to an overestimation of SVM-based virtual screening performance compared to search conditions that are more relevant for practical applications.
Shin, Woong-Hee; Kihara, Daisuke
2018-01-01
Virtual screening is a computational technique for predicting a potent binding compound for a receptor protein from a ligand library. It has been a widely used in the drug discovery field to reduce the efforts of medicinal chemists to find hit compounds by experiments.Here, we introduce our novel structure-based virtual screening program, PL-PatchSurfer, which uses molecular surface representation with the three-dimensional Zernike descriptors, which is an effective mathematical representation for identifying physicochemical complementarities between local surfaces of a target protein and a ligand. The advantage of the surface-patch description is its tolerance on a receptor and compound structure variation. PL-PatchSurfer2 achieves higher accuracy on apo form and computationally modeled receptor structures than conventional structure-based virtual screening programs. Thus, PL-PatchSurfer2 opens up an opportunity for targets that do not have their crystal structures. The program is provided as a stand-alone program at http://kiharalab.org/plps2 . We also provide files for two ligand libraries, ChEMBL and ZINC Drug-like.
Automated tool for virtual screening and pharmacology-based pathway prediction and analysis
Directory of Open Access Journals (Sweden)
Sugandh Kumar
2017-10-01
Full Text Available The virtual screening is an effective tool for the lead identification in drug discovery. However, there are limited numbers of crystal structures available as compared to the number of biological sequences which makes (Structure Based Drug Discovery SBDD a difficult choice. The current tool is an attempt to automate the protein structure modelling and automatic virtual screening followed by pharmacology-based prediction and analysis. Starting from sequence(s, this tool automates protein structure modelling, binding site identification, automated docking, ligand preparation, post docking analysis and identification of hits in the biological pathways that can be modulated by a group of ligands. This automation helps in the characterization of ligands selectivity and action of ligands on a complex biological molecular network as well as on individual receptor. The judicial combination of the ligands binding different receptors can be used to inhibit selective biological pathways in a disease. This tool also allows the user to systemically investigate network-dependent effects of a drug or drug candidate.
Sensor Webs and Virtual Globes: Enabling Understanding of Changes in a partially Glaciated Watershed
Heavner, M.; Fatland, D. R.; Habermann, M.; Berner, L.; Hood, E.; Connor, C.; Galbraith, J.; Knuth, E.; O'Brien, W.
2008-12-01
The University of Alaska Southeast is currently implementing a sensor web identified as the SouthEast Alaska MOnitoring Network for Science, Telecommunications, Education, and Research (SEAMONSTER). SEAMONSTER is operating in the partially glaciated Mendenhall and Lemon Creek Watersheds, in the Juneau area, on the margins of the Juneau Icefield. These watersheds are studied for both 1. long term monitoring of changes, and 2. detection and analysis of transient events (such as glacier lake outburst floods). The heterogeneous sensors (meteorologic, dual frequency GPS, water quality, lake level, etc), power and bandwidth constraints, and competing time scales of interest require autonomous reactivity of the sensor web. They also present challenges for operational management of the sensor web. The harsh conditions on the glaciers provide additional operating constraints. The tight integration of the sensor web and virtual global enabling technology enhance the project in multiple ways. We are utilizing virtual globe infrastructures to enhance both sensor web management and data access. SEAMONSTER utilizes virtual globes for education and public outreach, sensor web management, data dissemination, and enabling collaboration. Using a PosgreSQL with GIS extensions database coupled to the Open Geospatial Consortium (OGC) Geoserver, we generate near-real-time auto-updating geobrowser files of the data in multiple OGC standard formats (e.g KML, WCS). Additionally, embedding wiki pages in this database allows the development of a geospatially aware wiki describing the projects for better public outreach and education. In this presentation we will describe how we have implemented these technologies to date, the lessons learned, and our efforts towards greater OGC standard implementation. A major focus will be on demonstrating how geobrowsers and virtual globes have made this project possible.
Energy Technology Data Exchange (ETDEWEB)
Zhang, Liying; Sedykh, Alexander; Tripathi, Ashutosh [Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC (United States); Zhu, Hao [The Rutgers Center for Computational and Integrative Biology, Rutgers University, Camden, NJ (United States); Department of Chemistry, Rutgers University, Camden, NJ (United States); Afantitis, Antreas; Mouchlis, Varnavas D.; Melagraki, Georgia [NovaMechanics Ltd., Nicosia (Cyprus); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC (United States)
2013-10-01
Identification of endocrine disrupting chemicals is one of the important goals of environmental chemical hazard screening. We report on the development of validated in silico predictors of chemicals likely to cause estrogen receptor (ER)-mediated endocrine disruption to facilitate their prioritization for future screening. A database of relative binding affinity of a large number of ERα and/or ERβ ligands was assembled (546 for ERα and 137 for ERβ). Both single-task learning (STL) and multi-task learning (MTL) continuous quantitative structure–activity relationship (QSAR) models were developed for predicting ligand binding affinity to ERα or ERβ. High predictive accuracy was achieved for ERα binding affinity (MTL R{sup 2} = 0.71, STL R{sup 2} = 0.73). For ERβ binding affinity, MTL models were significantly more predictive (R{sup 2} = 0.53, p < 0.05) than STL models. In addition, docking studies were performed on a set of ER agonists/antagonists (67 agonists and 39 antagonists for ERα, 48 agonists and 32 antagonists for ERβ, supplemented by putative decoys/non-binders) using the following ER structures (in complexes with respective ligands) retrieved from the Protein Data Bank: ERα agonist (PDB ID: 1L2I), ERα antagonist (PDB ID: 3DT3), ERβ agonist (PDB ID: 2NV7), and ERβ antagonist (PDB ID: 1L2J). We found that all four ER conformations discriminated their corresponding ligands from presumed non-binders. Finally, both QSAR models and ER structures were employed in parallel to virtually screen several large libraries of environmental chemicals to derive a ligand- and structure-based prioritized list of putative estrogenic compounds to be used for in vitro and in vivo experimental validation. - Highlights: • This is the largest curated dataset inclusive of ERα and β (the latter is unique). • New methodology that for the first time affords acceptable ERβ models. • A combination of QSAR and docking enables prediction of affinity and function.
International Nuclear Information System (INIS)
Zhang, Liying; Sedykh, Alexander; Tripathi, Ashutosh; Zhu, Hao; Afantitis, Antreas; Mouchlis, Varnavas D.; Melagraki, Georgia; Rusyn, Ivan; Tropsha, Alexander
2013-01-01
Identification of endocrine disrupting chemicals is one of the important goals of environmental chemical hazard screening. We report on the development of validated in silico predictors of chemicals likely to cause estrogen receptor (ER)-mediated endocrine disruption to facilitate their prioritization for future screening. A database of relative binding affinity of a large number of ERα and/or ERβ ligands was assembled (546 for ERα and 137 for ERβ). Both single-task learning (STL) and multi-task learning (MTL) continuous quantitative structure–activity relationship (QSAR) models were developed for predicting ligand binding affinity to ERα or ERβ. High predictive accuracy was achieved for ERα binding affinity (MTL R 2 = 0.71, STL R 2 = 0.73). For ERβ binding affinity, MTL models were significantly more predictive (R 2 = 0.53, p < 0.05) than STL models. In addition, docking studies were performed on a set of ER agonists/antagonists (67 agonists and 39 antagonists for ERα, 48 agonists and 32 antagonists for ERβ, supplemented by putative decoys/non-binders) using the following ER structures (in complexes with respective ligands) retrieved from the Protein Data Bank: ERα agonist (PDB ID: 1L2I), ERα antagonist (PDB ID: 3DT3), ERβ agonist (PDB ID: 2NV7), and ERβ antagonist (PDB ID: 1L2J). We found that all four ER conformations discriminated their corresponding ligands from presumed non-binders. Finally, both QSAR models and ER structures were employed in parallel to virtually screen several large libraries of environmental chemicals to derive a ligand- and structure-based prioritized list of putative estrogenic compounds to be used for in vitro and in vivo experimental validation. - Highlights: • This is the largest curated dataset inclusive of ERα and β (the latter is unique). • New methodology that for the first time affords acceptable ERβ models. • A combination of QSAR and docking enables prediction of affinity and function. • The results
Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B.; Szukala, Richard; Johnson, Michael E.; Hevener, Kirk E.
2013-01-01
A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, drug-like, and ADMET filters were applied to the reported hits to assess the quality of compounds reported and a careful analysis of a subset of the studies which presented hit optimization was performed. This data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, defining hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria. PMID:23688234
Zhu, Tian; Cao, Shuyi; Su, Pin-Chih; Patel, Ram; Shah, Darshan; Chokshi, Heta B; Szukala, Richard; Johnson, Michael E; Hevener, Kirk E
2013-09-12
A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses, and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, druglike, and ADMET filters were applied to the reported hits to assess the quality of compounds reported, and a careful analysis of a subset of the studies that presented hit optimization was performed. These data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, definition of hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria.
The Stanford Automated Mounter: Enabling High-Throughput Protein Crystal Screening at SSRL
International Nuclear Information System (INIS)
Smith, C.A.; Cohen, A.E.
2009-01-01
The macromolecular crystallography experiment lends itself perfectly to high-throughput technologies. The initial steps including the expression, purification, and crystallization of protein crystals, along with some of the later steps involving data processing and structure determination have all been automated to the point where some of the last remaining bottlenecks in the process have been crystal mounting, crystal screening, and data collection. At the Stanford Synchrotron Radiation Laboratory, a National User Facility that provides extremely brilliant X-ray photon beams for use in materials science, environmental science, and structural biology research, the incorporation of advanced robotics has enabled crystals to be screened in a true high-throughput fashion, thus dramatically accelerating the final steps. Up to 288 frozen crystals can be mounted by the beamline robot (the Stanford Auto-Mounting System) and screened for diffraction quality in a matter of hours without intervention. The best quality crystals can then be remounted for the collection of complete X-ray diffraction data sets. Furthermore, the entire screening and data collection experiment can be controlled from the experimenter's home laboratory by means of advanced software tools that enable network-based control of the highly automated beamlines.
An effective docking strategy for virtual screening based on multi-objective optimization algorithm
Directory of Open Access Journals (Sweden)
Kang Ling
2009-02-01
Full Text Available Abstract Background Development of a fast and accurate scoring function in virtual screening remains a hot issue in current computer-aided drug research. Different scoring functions focus on diverse aspects of ligand binding, and no single scoring can satisfy the peculiarities of each target system. Therefore, the idea of a consensus score strategy was put forward. Integrating several scoring functions, consensus score re-assesses the docked conformations using a primary scoring function. However, it is not really robust and efficient from the perspective of optimization. Furthermore, to date, the majority of available methods are still based on single objective optimization design. Results In this paper, two multi-objective optimization methods, called MOSFOM, were developed for virtual screening, which simultaneously consider both the energy score and the contact score. Results suggest that MOSFOM can effectively enhance enrichment and performance compared with a single score. For three different kinds of binding sites, MOSFOM displays an excellent ability to differentiate active compounds through energy and shape complementarity. EFMOGA performed particularly well in the top 2% of database for all three cases, whereas MOEA_Nrg and MOEA_Cnt performed better than the corresponding individual scoring functions if the appropriate type of binding site was selected. Conclusion The multi-objective optimization method was successfully applied in virtual screening with two different scoring functions that can yield reasonable binding poses and can furthermore, be ranked with the potentially compromised conformations of each compound, abandoning those conformations that can not satisfy overall objective functions.
Structure-based virtual screening of molecular libraries as cdk2 inhibitors
International Nuclear Information System (INIS)
Riaz, U.; Khaleeq, M.
2011-01-01
CDK2 inhibitor is an important target in multiple processes associated with tumor growth and development, including proliferation, neovascularization, and metastasis. In this study, hit identification was performed by virtual screening of commercial and in-house compound libraries. Docking studies for the hits were performed, and scoring functions were used to evaluate the docking results and to rank ligand-binding affinities. Subsequently, hit optimization for potent and selective candidate CDK2 inhibitors was performed through focused library design and docking analyses. Consequently, we report that a novel compound with an IC50 value of 89 nM, representing 2-Amino-4,6-di-(4',6'-dibromophenyl)pyrimidine 1, is highly selective for CDK2 inhibitors. The docking structure of compound 1 with CDK2 inhibitor disclosed that the NH moiety and pyrimidine ring appeared to fit tightly into the hydrophobic pocket of CDK2 inhibitor. Additionally, the pyrimidine NH forms a hydrogen bond with the carboxyl group of Asp348. These results confirm the successful application of virtual screening studies in the lead discovery process, and suggest that our novel compound can be an effective CDK2 inhibitor candidate for further lead optimization. (author)
Hristozov, Dimitar P; Oprea, Tudor I; Gasteiger, Johann
2007-01-01
Four different ligand-based virtual screening scenarios are studied: (1) prioritizing compounds for subsequent high-throughput screening (HTS); (2) selecting a predefined (small) number of potentially active compounds from a large chemical database; (3) assessing the probability that a given structure will exhibit a given activity; (4) selecting the most active structure(s) for a biological assay. Each of the four scenarios is exemplified by performing retrospective ligand-based virtual screening for eight different biological targets using two large databases--MDDR and WOMBAT. A comparison between the chemical spaces covered by these two databases is presented. The performance of two techniques for ligand--based virtual screening--similarity search with subsequent data fusion (SSDF) and novelty detection with Self-Organizing Maps (ndSOM) is investigated. Three different structure representations--2,048-dimensional Daylight fingerprints, topological autocorrelation weighted by atomic physicochemical properties (sigma electronegativity, polarizability, partial charge, and identity) and radial distribution functions weighted by the same atomic physicochemical properties--are compared. Both methods were found applicable in scenario one. The similarity search was found to perform slightly better in scenario two while the SOM novelty detection is preferred in scenario three. No method/descriptor combination achieved significant success in scenario four.
DEFF Research Database (Denmark)
Markt, Patrick; Petersen, Rasmus K; Flindt, Esben N
2008-01-01
Peroxisome proliferator-activated receptors (PPARs) are important targets for drugs used in the treatment of atherosclerosis, dyslipidaemia, obesity, type 2 diabetes, and other diseases caused by abnormal regulation of the glucose and lipid metabolism. We applied a virtual screening workflow base...
The anatomy of the grid : enabling scalable virtual organizations.
Energy Technology Data Exchange (ETDEWEB)
Foster, I.; Kesselman, C.; Tuecke, S.; Mathematics and Computer Science; Univ. of Chicago; Univ. of Southern California
2001-10-01
'Grid' computing has emerged as an important new field, distinguished from conventional distributed computing by its focus on large-scale resource sharing, innovative applications, and, in some cases, high performance orientation. In this article, the authors define this new field. First, they review the 'Grid problem,' which is defined as flexible, secure, coordinated resource sharing among dynamic collections of individuals, institutions, and resources -- what is referred to as virtual organizations. In such settings, unique authentication, authorization, resource access, resource discovery, and other challenges are encountered. It is this class of problem that is addressed by Grid technologies. Next, the authors present an extensible and open Grid architecture, in which protocols, services, application programming interfaces, and software development kits are categorized according to their roles in enabling resource sharing. The authors describe requirements that they believe any such mechanisms must satisfy and discuss the importance of defining a compact set of intergrid protocols to enable interoperability among different Grid systems. Finally, the authors discuss how Grid technologies relate to other contemporary technologies, including enterprise integration, application service provider, storage service provider, and peer-to-peer computing. They maintain that Grid concepts and technologies complement and have much to contribute to these other approaches.
Gerig, Nicolas; Mayo, Johnathan; Baur, Kilian; Wittmann, Frieder; Riener, Robert; Wolf, Peter
2018-01-01
Goal-directed reaching for real-world objects by humans is enabled through visual depth cues. In virtual environments, the number and quality of available visual depth cues is limited, which may affect reaching performance and quality of reaching movements. We assessed three-dimensional reaching movements in five experimental groups each with ten healthy volunteers. Three groups used a two-dimensional computer screen and two groups used a head-mounted display. The first screen group received the typically recreated visual depth cues, such as aerial and linear perspective, occlusion, shadows, and texture gradients. The second screen group received an abstract minimal rendering lacking those. The third screen group received the cues of the first screen group and absolute depth cues enabled by retinal image size of a known object, which realized with visual renderings of the handheld device and a ghost handheld at the target location. The two head-mounted display groups received the same virtually recreated visual depth cues as the second or the third screen group respectively. Additionally, they could rely on stereopsis and motion parallax due to head-movements. All groups using the screen performed significantly worse than both groups using the head-mounted display in terms of completion time normalized by the straight-line distance to the target. Both groups using the head-mounted display achieved the optimal minimum in number of speed peaks and in hand path ratio, indicating that our subjects performed natural movements when using a head-mounted display. Virtually recreated visual depth cues had a minor impact on reaching performance. Only the screen group with rendered handhelds could outperform the other screen groups. Thus, if reaching performance in virtual environments is in the main scope of a study, we suggest applying a head-mounted display. Otherwise, when two-dimensional screens are used, achievable performance is likely limited by the reduced depth
Kalliokoski, Tuomo; Ronkko, Toni; Poso, Antti
2008-06-01
Algorithms were developed for ligand-based virtual screening of molecular databases. FieldChopper (FC) is based on the discretization of the electrostatic and van der Waals field into three classes. A model is built from a set of superimposed active molecules. The similarity of the compounds in the database to the model is then calculated using matrices that define scores for comparing field values of different categories. The method was validated using 12 publicly available data sets by comparing the method to the electrostatic similarity comparison program EON. The results suggest that FC is competitive with more complex descriptors and could be used as a molecular sieve in virtual screening experiments when multiple active ligands are known.
Estimation of the applicability domain of kernel-based machine learning models for virtual screening
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Fechner Nikolas
2010-03-01
Full Text Available Abstract Background The virtual screening of large compound databases is an important application of structural-activity relationship models. Due to the high structural diversity of these data sets, it is impossible for machine learning based QSAR models, which rely on a specific training set, to give reliable results for all compounds. Thus, it is important to consider the subset of the chemical space in which the model is applicable. The approaches to this problem that have been published so far mostly use vectorial descriptor representations to define this domain of applicability of the model. Unfortunately, these cannot be extended easily to structured kernel-based machine learning models. For this reason, we propose three approaches to estimate the domain of applicability of a kernel-based QSAR model. Results We evaluated three kernel-based applicability domain estimations using three different structured kernels on three virtual screening tasks. Each experiment consisted of the training of a kernel-based QSAR model using support vector regression and the ranking of a disjoint screening data set according to the predicted activity. For each prediction, the applicability of the model for the respective compound is quantitatively described using a score obtained by an applicability domain formulation. The suitability of the applicability domain estimation is evaluated by comparing the model performance on the subsets of the screening data sets obtained by different thresholds for the applicability scores. This comparison indicates that it is possible to separate the part of the chemspace, in which the model gives reliable predictions, from the part consisting of structures too dissimilar to the training set to apply the model successfully. A closer inspection reveals that the virtual screening performance of the model is considerably improved if half of the molecules, those with the lowest applicability scores, are omitted from the screening
Fechner, Nikolas; Jahn, Andreas; Hinselmann, Georg; Zell, Andreas
2010-03-11
The virtual screening of large compound databases is an important application of structural-activity relationship models. Due to the high structural diversity of these data sets, it is impossible for machine learning based QSAR models, which rely on a specific training set, to give reliable results for all compounds. Thus, it is important to consider the subset of the chemical space in which the model is applicable. The approaches to this problem that have been published so far mostly use vectorial descriptor representations to define this domain of applicability of the model. Unfortunately, these cannot be extended easily to structured kernel-based machine learning models. For this reason, we propose three approaches to estimate the domain of applicability of a kernel-based QSAR model. We evaluated three kernel-based applicability domain estimations using three different structured kernels on three virtual screening tasks. Each experiment consisted of the training of a kernel-based QSAR model using support vector regression and the ranking of a disjoint screening data set according to the predicted activity. For each prediction, the applicability of the model for the respective compound is quantitatively described using a score obtained by an applicability domain formulation. The suitability of the applicability domain estimation is evaluated by comparing the model performance on the subsets of the screening data sets obtained by different thresholds for the applicability scores. This comparison indicates that it is possible to separate the part of the chemspace, in which the model gives reliable predictions, from the part consisting of structures too dissimilar to the training set to apply the model successfully. A closer inspection reveals that the virtual screening performance of the model is considerably improved if half of the molecules, those with the lowest applicability scores, are omitted from the screening. The proposed applicability domain formulations
Zhang, Baofeng; D'Erasmo, Michael P; Murelli, Ryan P; Gallicchio, Emilio
2016-09-30
We report the results of a binding free energy-based virtual screening campaign of a library of 77 α-hydroxytropolone derivatives against the challenging RNase H active site of the reverse transcriptase (RT) enzyme of human immunodeficiency virus-1. Multiple protonation states, rotamer states, and binding modalities of each compound were individually evaluated. The work involved more than 300 individual absolute alchemical binding free energy parallel molecular dynamics calculations and over 1 million CPU hours on national computing clusters and a local campus computational grid. The thermodynamic and structural measures obtained in this work rationalize a series of characteristics of this system useful for guiding future synthetic and biochemical efforts. The free energy model identified key ligand-dependent entropic and conformational reorganization processes difficult to capture using standard docking and scoring approaches. Binding free energy-based optimization of the lead compounds emerging from the virtual screen has yielded four compounds with very favorable binding properties, which will be the subject of further experimental investigations. This work is one of the few reported applications of advanced-binding free energy models to large-scale virtual screening and optimization projects. It further demonstrates that, with suitable algorithms and automation, advanced-binding free energy models can have a useful role in early-stage drug-discovery programs.
Torktaz, Ibrahim; Mohamadhashem, Faezeh; Esmaeili, Abolghasem; Behjati, Mohaddeseh; Sharifzadeh, Sara
2013-01-01
Metastasis is a crucial aspect of cancer. Macrophage stimulating protein (MSP) is a single chain protein and can be cleaved by serum proteases. MSP has several roles in metastasis. In this in silico study, MSP as a metastatic agent was considered as a drug target. Crystallographic structure of MSP was retrieved from protein data bank. To find a chemical inhibitor of MSP, a library of KEGG compounds was screened and 1000 shape complemented ligands were retrieved with FindSite algorithm. Molegro Virtual Docker (MVD) software was used for docking simulation of shape complemented ligands against MSP. Moldock score was used as scoring function for virtual screening and potential inhibitors with more negative binding energy were obtained. PLANS scoring function was used for revaluation of virtual screening data. The top found chemical had binding affinity of -183.55 based on MolDock score and equal to -66.733 PLANTs score to MSP structure. Based on pharmacophore model of potential inhibitor, this study suggests that the chemical which was found in this research and its derivate can be used for subsequent laboratory studies.
Davidson, Dennisa; Evans, Lois
2018-03-01
To explore online study groups as augmentation tools in preparing for the Royal Australian and New Zealand College of Psychiatrists Observed Structured Clinical Examinations (OSCE) for fellowship. An online survey of New Zealand trainees was carried out to assess exam preparedness and openness to virtual study groups and results analysed. Relevant material around virtual study groups for fellowship examinations was reviewed and used to inform a pilot virtual study group. Four New Zealand trainees took part in the pilot project, looking at using a virtual platform to augment OSCE preparation. Of the 50 respondents 36% felt adequately prepared for the OSCE. Sixty-four per cent were interested in using a virtual platform to augment their study. Virtual study groups were noted to be especially important for rural trainees, none of whom felt able to form study groups for themselves. The pilot virtual study group was trialled successfully. All four trainees reported the experience as subjectively beneficial to their examination preparation. Virtual platforms hold promise as an augmentation strategy for exam preparation, especially for rural trainees who are more geographically isolated and less likely to have peers preparing for the same examinations.
2011-01-01
Background The performance of 3D-based virtual screening similarity functions is affected by the applied conformations of compounds. Therefore, the results of 3D approaches are often less robust than 2D approaches. The application of 3D methods on multiple conformer data sets normally reduces this weakness, but entails a significant computational overhead. Therefore, we developed a special conformational space encoding by means of Gaussian mixture models and a similarity function that operates on these models. The application of a model-based encoding allows an efficient comparison of the conformational space of compounds. Results Comparisons of our 4D flexible atom-pair approach with over 15 state-of-the-art 2D- and 3D-based virtual screening similarity functions on the 40 data sets of the Directory of Useful Decoys show a robust performance of our approach. Even 3D-based approaches that operate on multiple conformers yield inferior results. The 4D flexible atom-pair method achieves an averaged AUC value of 0.78 on the filtered Directory of Useful Decoys data sets. The best 2D- and 3D-based approaches of this study yield an AUC value of 0.74 and 0.72, respectively. As a result, the 4D flexible atom-pair approach achieves an average rank of 1.25 with respect to 15 other state-of-the-art similarity functions and four different evaluation metrics. Conclusions Our 4D method yields a robust performance on 40 pharmaceutically relevant targets. The conformational space encoding enables an efficient comparison of the conformational space. Therefore, the weakness of the 3D-based approaches on single conformations is circumvented. With over 100,000 similarity calculations on a single desktop CPU, the utilization of the 4D flexible atom-pair in real-world applications is feasible. PMID:21733172
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Yunierkis Perez-Castillo
Full Text Available Gastric cancer is the third leading cause of cancer-related mortality worldwide and despite advances in prevention, diagnosis and therapy, it is still regarded as a global health concern. The efficacy of the therapies for gastric cancer is limited by a poor response to currently available therapeutic regimens. One of the reasons that may explain these poor clinical outcomes is the highly heterogeneous nature of this disease. In this sense, it is essential to discover new molecular agents capable of targeting various gastric cancer subtypes simultaneously. Here, we present a multi-objective approach for the ligand-based virtual screening discovery of chemical compounds simultaneously active against the gastric cancer cell lines AGS, NCI-N87 and SNU-1. The proposed approach relays in a novel methodology based on the development of ensemble models for the bioactivity prediction against each individual gastric cancer cell line. The methodology includes the aggregation of one ensemble per cell line using a desirability-based algorithm into virtual screening protocols. Our research leads to the proposal of a multi-targeted virtual screening protocol able to achieve high enrichment of known chemicals with anti-gastric cancer activity. Specifically, our results indicate that, using the proposed protocol, it is possible to retrieve almost 20 more times multi-targeted compounds in the first 1% of the ranked list than what is expected from a uniform distribution of the active ones in the virtual screening database. More importantly, the proposed protocol attains an outstanding initial enrichment of known multi-targeted anti-gastric cancer agents.
Zaveri, Kunal; Kiranmayi, Patnala
2017-01-01
The prevalence of multi-drug resistance S. aureus is one of the most challenging tasks for the treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis. To screen the potential MurE inhibitor by in silico approach and evaluate the best potential lead molecule by in vitro methods. In the current study, we have employed structure based virtual screening targeting the active site of MurE, followed by Molecular dynamics and in vitro studies. Virtual screening resulted in successful screening of potential lead molecule ((2R)-2-[[1-[(2R)- 2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan). The molecular dynamics of the MurE and Lead molecule complex emphasizes that lead molecule has shown stable interactions with active site residues Asp 406 and with Glu 460. In vitro studies demonstrate that the lead molecule shows antibacterial activity close to standard antibiotic Vancomycin and higher than that of Ampicillin, Streptomycin and Rifampicin. The MIC of lead molecule at 50μg/mL was observed to be 3.75 μg/mL, MBC being bactericidal with value of 6.25 μg/mL, cytotoxicity showing 34.44% and IC50 of 40.06μg/mL. These results suggest ((2R)-2-[[1-[(2R)-2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan) as a promising lead molecule for developing a MurE inhibitor against treatment of S. aureus infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Ibrahim Torktaz
2013-09-01
Full Text Available Introduction: Metastasis is a crucial aspect of cancer. Macrophage stimulating protein (MSP is a single chain protein and can be cleaved by serum proteases. MSP has several roles in metastasis. In this in silico study, MSP as a metastatic agent was considered as a drug target. Methods: Crystallographic structure of MSP was retrieved from protein data bank. To find a chemical inhibitor of MSP, a library of KEGG compounds was screened and 1000 shape complemented ligands were retrieved with FindSite algorithm. Molegro Virtual Docker (MVD software was used for docking simulation of shape complemented ligands against MSP. Moldock score was used as scoring function for virtual screening and potential inhibitors with more negative binding energy were obtained. PLANS scoring function was used for revaluation of virtual screening data. Results: The top found chemical had binding affinity of -183.55 based on MolDock score and equal to -66.733 PLANTs score to MSP structure. Conclusion: Based on pharmacophore model of potential inhibitor, this study suggests that the chemical which was found in this research and its derivate can be used for subsequent laboratory studies.
The Discovery of Aurora Kinase Inhibitor by Multi-Docking-Based Virtual Screening
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Jun-Tae Kim
2014-11-01
Full Text Available We report the discovery of aurora kinase inhibitor using the fragment-based virtual screening by multi-docking strategy. Among a number of fragments collected from eMololecules, we found four fragment molecules showing potent activity (>50% at 100 μM against aurora kinase. Based on the explored fragment scaffold, we selected two compounds in our synthesized library and validated the biological activity against Aurora kinase.
Fleming, Michael; Olsen, Dale; Stathes, Hilary; Boteler, Laura; Grossberg, Paul; Pfeifer, Judie; Schiro, Stephanie; Banning, Jane; Skochelak, Susan
2009-01-01
Background Educating physicians and other health care professionals to identify and treat patients who drink above recommended limits is an ongoing challenge. Methods An educational Randomized Control Trial (RCT) was conducted to test the ability of a stand alone training simulation to improve the clinical skills of health care professionals in alcohol screening and intervention. The “virtual reality simulation” combines video, voice recognition and non branching logic to create an interactive environment that allows trainees to encounter complex social cues and realistic interpersonal exchanges. The simulation includes 707 questions and statements and 1207 simulated patient responses. Results A sample of 102 health care professionals (10 physicians; 30 physician assistants [PAs] or nurse practitioners [NPs]; 36 medical students; 26 pharmacy, PA or NP students) were randomly assigned to no training (n=51) or a computer based virtual reality intervention (n=51). Subjects in both groups had similar pre-test standardized patient alcohol screening skill scores – 53.2 (experimental) vs. 54.4 (controls), 52.2 vs. 53.7 alcohol brief intervention skills, and 42.9 vs. 43.5 alcohol referral skills. Following repeated practice with the simulation there were significant increases in the scores of the experimental group at 6 months post-randomization compared to the control group for the screening (67.7 vs. 58.1, pvirtual reality simulation to demonstrate an increase in the alcohol screening and brief intervention skills of health care professionals. PMID:19587253
Virtual screening of inorganic materials synthesis parameters with deep learning
Kim, Edward; Huang, Kevin; Jegelka, Stefanie; Olivetti, Elsa
2017-12-01
Virtual materials screening approaches have proliferated in the past decade, driven by rapid advances in first-principles computational techniques, and machine-learning algorithms. By comparison, computationally driven materials synthesis screening is still in its infancy, and is mired by the challenges of data sparsity and data scarcity: Synthesis routes exist in a sparse, high-dimensional parameter space that is difficult to optimize over directly, and, for some materials of interest, only scarce volumes of literature-reported syntheses are available. In this article, we present a framework for suggesting quantitative synthesis parameters and potential driving factors for synthesis outcomes. We use a variational autoencoder to compress sparse synthesis representations into a lower dimensional space, which is found to improve the performance of machine-learning tasks. To realize this screening framework even in cases where there are few literature data, we devise a novel data augmentation methodology that incorporates literature synthesis data from related materials systems. We apply this variational autoencoder framework to generate potential SrTiO3 synthesis parameter sets, propose driving factors for brookite TiO2 formation, and identify correlations between alkali-ion intercalation and MnO2 polymorph selection.
The Virtual Learning Commons (VLC): Enabling Co-Innovation Across Disciplines
Pennington, D. D.; Gandara, A.; Del Rio, N.
2014-12-01
A key challenge for scientists addressing grand-challenge problems is identifying, understanding, and integrating potentially relevant methods, models and tools that that are rapidly evolving in the informatics community. Such tools are essential for effectively integrating data and models in complex research projects, yet it is often difficult to know what tools are available and it is not easy to understand or evaluate how they might be used in a given research context. The goal of the National Science Foundation-funded Virtual Learning Commons (VLC) is to improve awareness and understanding of emerging methodologies and technologies, facilitate individual and group evaluation of these, and trace the impact of innovations within and across teams, disciplines, and communities. The VLC is a Web-based social bookmarking site designed specifically to support knowledge exchange in research communities. It is founded on well-developed models of technology adoption, diffusion of innovation, and experiential learning. The VLC makes use of Web 2.0 (Social Web) and Web 3.0 (Semantic Web) approaches. Semantic Web approaches enable discovery of potentially relevant methods, models, and tools, while Social Web approaches enable collaborative learning about their function. The VLC is under development and the first release is expected Fall 2014.
Chaput, Ludovic; Martinez-Sanz, Juan; Quiniou, Eric; Rigolet, Pascal; Saettel, Nicolas; Mouawad, Liliane
2016-01-01
In drug design, one may be confronted to the problem of finding hits for targets for which no small inhibiting molecules are known and only low-throughput experiments are available (like ITC or NMR studies), two common difficulties encountered in a typical academic setting. Using a virtual screening strategy like docking can alleviate some of the problems and save a considerable amount of time by selecting only top-ranking molecules, but only if the method is very efficient, i.e. when a good proportion of actives are found in the 1-10 % best ranked molecules. The use of several programs (in our study, Gold, Surflex, FlexX and Glide were considered) shows a divergence of the results, which presents a difficulty in guiding the experiments. To overcome this divergence and increase the yield of the virtual screening, we created the standard deviation consensus (SDC) and variable SDC (vSDC) methods, consisting of the intersection of molecule sets from several virtual screening programs, based on the standard deviations of their ranking distributions. SDC allowed us to find hits for two new protein targets by testing only 9 and 11 small molecules from a chemical library of circa 15,000 compounds. Furthermore, vSDC, when applied to the 102 proteins of the DUD-E benchmarking database, succeeded in finding more hits than any of the four isolated programs for 13-60 % of the targets. In addition, when only 10 molecules of each of the 102 chemical libraries were considered, vSDC performed better in the number of hits found, with an improvement of 6-24 % over the 10 best-ranked molecules given by the individual docking programs.Graphical abstractIn drug design, for a given target and a given chemical library, the results obtained with different virtual screening programs are divergent. So how to rationally guide the experimental tests, especially when only a few number of experiments can be made? The variable Standard Deviation Consensus (vSDC) method was developed to
Kaserer, Teresa; Temml, Veronika; Kutil, Zsofia; Vanek, Tomas; Landa, Premysl; Schuster, Daniela
2015-01-01
Computational methods can be applied in drug development for the identification of novel lead candidates, but also for the prediction of pharmacokinetic properties and potential adverse effects, thereby aiding to prioritize and identify the most promising compounds. In principle, several techniques are available for this purpose, however, which one is the most suitable for a specific research objective still requires further investigation. Within this study, the performance of several programs, representing common virtual screening methods, was compared in a prospective manner. First, we selected top-ranked virtual screening hits from the three methods pharmacophore modeling, shape-based modeling, and docking. For comparison, these hits were then additionally predicted by external pharmacophore- and 2D similarity-based bioactivity profiling tools. Subsequently, the biological activities of the selected hits were assessed in vitro, which allowed for evaluating and comparing the prospective performance of the applied tools. Although all methods performed well, considerable differences were observed concerning hit rates, true positive and true negative hits, and hitlist composition. Our results suggest that a rational selection of the applied method represents a powerful strategy to maximize the success of a research project, tightly linked to its aims. We employed cyclooxygenase as application example, however, the focus of this study lied on highlighting the differences in the virtual screening tool performances and not in the identification of novel COX-inhibitors. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian
2011-06-01
The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.
Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian
2011-06-01
The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.
Performance of machine-learning scoring functions in structure-based virtual screening.
Wójcikowski, Maciej; Ballester, Pedro J; Siedlecki, Pawel
2017-04-25
Classical scoring functions have reached a plateau in their performance in virtual screening and binding affinity prediction. Recently, machine-learning scoring functions trained on protein-ligand complexes have shown great promise in small tailored studies. They have also raised controversy, specifically concerning model overfitting and applicability to novel targets. Here we provide a new ready-to-use scoring function (RF-Score-VS) trained on 15 426 active and 893 897 inactive molecules docked to a set of 102 targets. We use the full DUD-E data sets along with three docking tools, five classical and three machine-learning scoring functions for model building and performance assessment. Our results show RF-Score-VS can substantially improve virtual screening performance: RF-Score-VS top 1% provides 55.6% hit rate, whereas that of Vina only 16.2% (for smaller percent the difference is even more encouraging: RF-Score-VS top 0.1% achieves 88.6% hit rate for 27.5% using Vina). In addition, RF-Score-VS provides much better prediction of measured binding affinity than Vina (Pearson correlation of 0.56 and -0.18, respectively). Lastly, we test RF-Score-VS on an independent test set from the DEKOIS benchmark and observed comparable results. We provide full data sets to facilitate further research in this area (http://github.com/oddt/rfscorevs) as well as ready-to-use RF-Score-VS (http://github.com/oddt/rfscorevs_binary).
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Yuri Pevzner
2014-05-01
Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.
Directory of Open Access Journals (Sweden)
Yuri Pevzner
2015-08-01
Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.
Sun, Yunan; Zhou, Hui; Zhu, Hongmei; Leung, Siu-wai
2016-01-25
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase, and its dysregulation can lead to ageing, diabetes, and cancer. From 346 experimentally confirmed SIRT1 inhibitors, an inhibitor structure pattern was generated by inductive logic programming (ILP) with DMax Chemistry Assistant software. The pattern contained amide, amine, and hetero-aromatic five-membered rings, each of which had a hetero-atom and an unsubstituted atom at a distance of 2. According to this pattern, a ligand-based virtual screening of 1 444 880 active compounds from Chinese herbs identified 12 compounds as inhibitors of SIRT1. Three compounds (ZINC08790006, ZINC08792229, and ZINC08792355) had high affinity (-7.3, -7.8, and -8.6 kcal/mol, respectively) for SIRT1 as estimated by molecular docking software AutoDock Vina. This study demonstrated a use of ILP and background knowledge in machine learning to facilitate virtual screening.
Energy Technology Data Exchange (ETDEWEB)
Dinda, Peter August [Northwestern Univ., Evanston, IL (United States)
2015-03-17
This report describes the activities, findings, and products of the Northwestern University component of the "Enabling Exascale Hardware and Software Design through Scalable System Virtualization" project. The purpose of this project has been to extend the state of the art of systems software for high-end computing (HEC) platforms, and to use systems software to better enable the evaluation of potential future HEC platforms, for example exascale platforms. Such platforms, and their systems software, have the goal of providing scientific computation at new scales, thus enabling new research in the physical sciences and engineering. Over time, the innovations in systems software for such platforms also become applicable to more widely used computing clusters, data centers, and clouds. This was a five-institution project, centered on the Palacios virtual machine monitor (VMM) systems software, a project begun at Northwestern, and originally developed in a previous collaboration between Northwestern University and the University of New Mexico. In this project, Northwestern (including via our subcontract to the University of Pittsburgh) contributed to the continued development of Palacios, along with other team members. We took the leadership role in (1) continued extension of support for emerging Intel and AMD hardware, (2) integration and performance enhancement of overlay networking, (3) connectivity with architectural simulation, (4) binary translation, and (5) support for modern Non-Uniform Memory Access (NUMA) hosts and guests. We also took a supporting role in support for specialized hardware for I/O virtualization, profiling, configurability, and integration with configuration tools. The efforts we led (1-5) were largely successful and executed as expected, with code and papers resulting from them. The project demonstrated the feasibility of a virtualization layer for HEC computing, similar to such layers for cloud or datacenter computing. For effort (3
Sastry, Madhavi; Lowrie, Jeffrey F; Dixon, Steven L; Sherman, Woody
2010-05-24
A systematic virtual screening study on 11 pharmaceutically relevant targets has been conducted to investigate the interrelation between 8 two-dimensional (2D) fingerprinting methods, 13 atom-typing schemes, 13 bit scaling rules, and 12 similarity metrics using the new cheminformatics package Canvas. In total, 157 872 virtual screens were performed to assess the ability of each combination of parameters to identify actives in a database screen. In general, fingerprint methods, such as MOLPRINT2D, Radial, and Dendritic that encode information about local environment beyond simple linear paths outperformed other fingerprint methods. Atom-typing schemes with more specific information, such as Daylight, Mol2, and Carhart were generally superior to more generic atom-typing schemes. Enrichment factors across all targets were improved considerably with the best settings, although no single set of parameters performed optimally on all targets. The size of the addressable bit space for the fingerprints was also explored, and it was found to have a substantial impact on enrichments. Small bit spaces, such as 1024, resulted in many collisions and in a significant degradation in enrichments compared to larger bit spaces that avoid collisions.
Vyas, Renu; Bapat, Sanket; Jain, Esha; Tambe, Sanjeev S; Karthikeyan, Muthukumarasamy; Kulkarni, Bhaskar D
2015-01-01
The ligand-based virtual screening of combinatorial libraries employs a number of statistical modeling and machine learning methods. A comprehensive analysis of the application of these methods for the diversity oriented virtual screening of biological targets/drug classes is presented here. A number of classification models have been built using three types of inputs namely structure based descriptors, molecular fingerprints and therapeutic category for performing virtual screening. The activity and affinity descriptors of a set of inhibitors of four target classes DHFR, COX, LOX and NMDA have been utilized to train a total of six classifiers viz. Artificial Neural Network (ANN), k nearest neighbor (k-NN), Support Vector Machine (SVM), Naïve Bayes (NB), Decision Tree--(DT) and Random Forest--(RF). Among these classifiers, the ANN was found as the best classifier with an AUC of 0.9 irrespective of the target. New molecular fingerprints based on pharmacophore, toxicophore and chemophore (PTC), were used to build the ANN models for each dataset. A good accuracy of 87.27% was obtained using 296 chemophoric binary fingerprints for the COX-LOX inhibitors compared to pharmacophoric (67.82%) and toxicophoric (70.64%). The methodology was validated on the classical Ames mutagenecity dataset of 4337 molecules. To evaluate it further, selectivity and promiscuity of molecules from five drug classes viz. anti-anginal, anti-convulsant, anti-depressant, anti-arrhythmic and anti-diabetic were studied. The TPC fingerprints computed for each category were able to capture the drug-class specific features using the k-NN classifier. These models can be useful for selecting optimal molecules for drug design.
Turk, Samo; Kovac, Andreja; Boniface, Audrey; Bostock, Julieanne M; Chopra, Ian; Blanot, Didier; Gobec, Stanislav
2009-03-01
The ATP-dependent Mur ligases (MurC, MurD, MurE and MurF) successively add L-Ala, D-Glu, meso-A(2)pm or L-Lys, and D-Ala-D-Ala to the nucleotide precursor UDP-MurNAc, and they represent promising targets for antibacterial drug discovery. We have used the molecular docking programme eHiTS for the virtual screening of 1990 compounds from the National Cancer Institute 'Diversity Set' on MurD and MurF. The 50 top-scoring compounds from screening on each enzyme were selected for experimental biochemical evaluation. Our approach of virtual screening and subsequent in vitro biochemical evaluation of the best ranked compounds has provided four novel MurD inhibitors (best IC(50)=10 microM) and one novel MurF inhibitor (IC(50)=63 microM).
Bolodurina, I. P.; Parfenov, D. I.
2018-01-01
We have elaborated a neural network model of virtual network flow identification based on the statistical properties of flows circulating in the network of the data center and characteristics that describe the content of packets transmitted through network objects. This enabled us to establish the optimal set of attributes to identify virtual network functions. We have established an algorithm for optimizing the placement of virtual data functions using the data obtained in our research. Our approach uses a hybrid method of visualization using virtual machines and containers, which enables to reduce the infrastructure load and the response time in the network of the virtual data center. The algorithmic solution is based on neural networks, which enables to scale it at any number of the network function copies.
Directory of Open Access Journals (Sweden)
Lin SH
2015-06-01
Full Text Available Shih-Hung Lin,1 Kao-Jean Huang,1,2 Ching-Feng Weng,1 David Shiuan1 1Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, Republic of China; 2Development Center of Biotechnology, Taipei, Taiwan, Republic of China Abstract: Cholesterol plays an important role in living cells. However, a very high level of cholesterol may lead to atherosclerosis. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A reductase is the key enzyme in the cholesterol biosynthesis pathway, and the statin-like drugs are inhibitors of human HMG-CoA reductase (hHMGR. The present study aimed to virtually screen for potential hHMGR inhibitors from natural product to discover hypolipidemic drug candidates with fewer side effects and lesser toxicities. We used the 3D structure 1HWK from the PDB (Protein Data Bank database of hHMGR as the target to screen for the strongly bound compounds from the traditional Chinese medicine database. Many interesting molecules including polyphenolic compounds, polisubstituted heterocyclics, and linear lipophilic alcohols were identified and their ADMET (absorption, disrtibution, metabolism, excretion, toxicity properties were predicted. Finally, four compounds were obtained for the in vitro validation experiments. The results indicated that curcumin and salvianolic acid C can effectively inhibit hHMGR, with IC50 (half maximal inhibitory concentration values of 4.3 µM and 8 µM, respectively. The present study also demonstrated the feasibility of discovering new drug candidates through structure-based virtual screening. Keywords: HMG-CoA reductase, virtual screening, curcumin, salvianolic acid C
Internet-Enabled High-Resolution Brain Mapping and Virtual Microscopy
Mikula, Shawn; Trotts, Issac; Stone, James M.; Jones, Edward G.
2007-01-01
Virtual microscopy involves the conversion of histological sections mounted on glass microscope slides to high resolution digital images. Virtual microscopy offers several advantages over traditional microscopy, including remote viewing and data-sharing, annotation, and various forms of data-mining.
Virtual screening by a new Clustering-based Weighted Similarity Extreme Learning Machine approach.
Pasupa, Kitsuchart; Kudisthalert, Wasu
2018-01-01
Machine learning techniques are becoming popular in virtual screening tasks. One of the powerful machine learning algorithms is Extreme Learning Machine (ELM) which has been applied to many applications and has recently been applied to virtual screening. We propose the Weighted Similarity ELM (WS-ELM) which is based on a single layer feed-forward neural network in a conjunction of 16 different similarity coefficients as activation function in the hidden layer. It is known that the performance of conventional ELM is not robust due to random weight selection in the hidden layer. Thus, we propose a Clustering-based WS-ELM (CWS-ELM) that deterministically assigns weights by utilising clustering algorithms i.e. k-means clustering and support vector clustering. The experiments were conducted on one of the most challenging datasets-Maximum Unbiased Validation Dataset-which contains 17 activity classes carefully selected from PubChem. The proposed algorithms were then compared with other machine learning techniques such as support vector machine, random forest, and similarity searching. The results show that CWS-ELM in conjunction with support vector clustering yields the best performance when utilised together with Sokal/Sneath(1) coefficient. Furthermore, ECFP_6 fingerprint presents the best results in our framework compared to the other types of fingerprints, namely ECFP_4, FCFP_4, and FCFP_6.
Ultrafast protein structure-based virtual screening with Panther
Niinivehmas, Sanna P.; Salokas, Kari; Lätti, Sakari; Raunio, Hannu; Pentikäinen, Olli T.
2015-10-01
Molecular docking is by far the most common method used in protein structure-based virtual screening. This paper presents Panther, a novel ultrafast multipurpose docking tool. In Panther, a simple shape-electrostatic model of the ligand-binding area of the protein is created by utilizing the protein crystal structure. The features of the possible ligands are then compared to the model by using a similarity search algorithm. On average, one ligand can be processed in a few minutes by using classical docking methods, whereas using Panther processing takes Panther protocol can be used in several applications, such as speeding up the early phases of drug discovery projects, reducing the number of failures in the clinical phase of the drug development process, and estimating the environmental toxicity of chemicals. Panther-code is available in our web pages (http://www.jyu.fi/panther) free of charge after registration.
Badrinarayan, Preethi; Sastry, G Narahari
2012-04-01
In this work, we introduce the development and application of a three-step scoring and filtering procedure for the design of type II p38 MAP kinase leads using allosteric fragments extracted from virtual screening hits. The design of the virtual screening filters is based on a thorough evaluation of docking methods, DFG-loop conformation, binding interactions and chemotype specificity of the 138 p38 MAP kinase inhibitors from Protein Data Bank bound to DFG-in and DFG-out conformations using Glide, GOLD and CDOCKER. A 40 ns molecular dynamics simulation with the apo, type I with DFG-in and type II with DFG-out forms was carried out to delineate the effects of structural variations on inhibitor binding. The designed docking-score and sub-structure filters were first tested on a dataset of 249 potent p38 MAP kinase inhibitors from seven diverse series and 18,842 kinase inhibitors from PDB, to gauge their capacity to discriminate between kinase and non-kinase inhibitors and likewise to selectively filter-in target-specific inhibitors. The designed filters were then applied in the virtual screening of a database of ten million (10⁷) compounds resulting in the identification of 100 hits. Based on their binding modes, 98 allosteric fragments were extracted from the hits and a fragment library was generated. New type II p38 MAP kinase leads were designed by tailoring the existing type I ATP site binders with allosteric fragments using a common urea linker. Target specific virtual screening filters can thus be easily developed for other kinases based on this strategy to retrieve target selective compounds. Copyright © 2012 Elsevier Inc. All rights reserved.
Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...
Energy Technology Data Exchange (ETDEWEB)
McLean, Larry R.; Zhang, Ying; Li, Hua; Li, Ziyu; Lukasczyk, Ulrike; Choi, Yong-Mi; Han, Zuoning; Prisco, Joy; Fordham, Jeremy; Tsay, Joseph T.; Reiling, Stephan; Vaz, Roy J.; Li, Yi; (Sanofi)
2010-10-28
Biochemical and X-ray crystallographic studies confirmed that hydroxyquinoline derivatives identified by virtual screening were actually covalent inhibitors of the MIF tautomerase. Adducts were formed by N-alkylation of the Pro-1 at the catalytic site with a loss of an amino group of the inhibitor.
International Nuclear Information System (INIS)
MILLER, MARC M.; YONEK JR., GEORGE A.
2001-01-01
Virtual Private Networking is a new communications technology that promises lower cost, more secure wide area communications by leveraging public networks such as the Internet. Sandia National Laboratories has embraced the technology for interconnecting remote sites to Sandia's corporate network, and for enabling remote access users for both dial-up and broadband access
Identification of LasR Ligands through a Virtual Screening Approach
DEFF Research Database (Denmark)
Skovstrup, Søren; Le Quement, Sebastian Thordal; Hansen, Thomas
2013-01-01
as an attractive therapeutic target for the next generation of antimicrobial agents. In the present study, a virtual screening workflow combining pharmacophore‐ and structure‐based approaches was used to identify new LasR ligands. Five novel inducers and three inhibitors of LasR activity were validated...... experimentally by use of a cell‐based assay. Interestingly, these compounds are molecularly distinct from the native signal molecule, N‐3‐oxododecanoyl‐L‐homoserine lactone (OHN), and may serve as lead structures for the design of new drugs. The binding modes of these compounds to the OHN binding site in Las......R were predicted and used to identify the key interactions that contribute to the induction and inhibition of LasR activity....
Cang, Zixuan; Mu, Lin; Wei, Guo-Wei
2018-01-01
This work introduces a number of algebraic topology approaches, including multi-component persistent homology, multi-level persistent homology, and electrostatic persistence for the representation, characterization, and description of small molecules and biomolecular complexes. In contrast to the conventional persistent homology, multi-component persistent homology retains critical chemical and biological information during the topological simplification of biomolecular geometric complexity. Multi-level persistent homology enables a tailored topological description of inter- and/or intra-molecular interactions of interest. Electrostatic persistence incorporates partial charge information into topological invariants. These topological methods are paired with Wasserstein distance to characterize similarities between molecules and are further integrated with a variety of machine learning algorithms, including k-nearest neighbors, ensemble of trees, and deep convolutional neural networks, to manifest their descriptive and predictive powers for protein-ligand binding analysis and virtual screening of small molecules. Extensive numerical experiments involving 4,414 protein-ligand complexes from the PDBBind database and 128,374 ligand-target and decoy-target pairs in the DUD database are performed to test respectively the scoring power and the discriminatory power of the proposed topological learning strategies. It is demonstrated that the present topological learning outperforms other existing methods in protein-ligand binding affinity prediction and ligand-decoy discrimination.
Mu, Lin
2018-01-01
This work introduces a number of algebraic topology approaches, including multi-component persistent homology, multi-level persistent homology, and electrostatic persistence for the representation, characterization, and description of small molecules and biomolecular complexes. In contrast to the conventional persistent homology, multi-component persistent homology retains critical chemical and biological information during the topological simplification of biomolecular geometric complexity. Multi-level persistent homology enables a tailored topological description of inter- and/or intra-molecular interactions of interest. Electrostatic persistence incorporates partial charge information into topological invariants. These topological methods are paired with Wasserstein distance to characterize similarities between molecules and are further integrated with a variety of machine learning algorithms, including k-nearest neighbors, ensemble of trees, and deep convolutional neural networks, to manifest their descriptive and predictive powers for protein-ligand binding analysis and virtual screening of small molecules. Extensive numerical experiments involving 4,414 protein-ligand complexes from the PDBBind database and 128,374 ligand-target and decoy-target pairs in the DUD database are performed to test respectively the scoring power and the discriminatory power of the proposed topological learning strategies. It is demonstrated that the present topological learning outperforms other existing methods in protein-ligand binding affinity prediction and ligand-decoy discrimination. PMID:29309403
Xing, Li; McDonald, Joseph J; Kolodziej, Steve A; Kurumbail, Ravi G; Williams, Jennifer M; Warren, Chad J; O'Neal, Janet M; Skepner, Jill E; Roberds, Steven L
2011-03-10
Structure-based virtual screening was applied to design combinatorial libraries to discover novel and potent soluble epoxide hydrolase (sEH) inhibitors. X-ray crystal structures revealed unique interactions for a benzoxazole template in addition to the conserved hydrogen bonds with the catalytic machinery of sEH. By exploitation of the favorable binding elements, two iterations of library design based on amide coupling were employed, guided principally by the docking results of the enumerated virtual products. Biological screening of the libraries demonstrated as high as 90% hit rate, of which over two dozen compounds were single digit nanomolar sEH inhibitors by IC(50) determination. In total the library design and synthesis produced more than 300 submicromolar sEH inhibitors. In cellular systems consistent activities were demonstrated with biochemical measurements. The SAR understanding of the benzoxazole template provides valuable insights into discovery of novel sEH inhibitors as therapeutic agents.
Yu, Miao; Gu, Qiong; Xu, Jun
2018-02-01
PI3Kα is a promising drug target for cancer chemotherapy. In this paper, we report a strategy of combing ligand-based and structure-based virtual screening to identify new PI3Kα inhibitors. First, naïve Bayesian (NB) learning models and a 3D-QSAR pharmacophore model were built based upon known PI3Kα inhibitors. Then, the SPECS library was screened by the best NB model. This resulted in virtual hits, which were validated by matching the structures against the pharmacophore models. The pharmacophore matched hits were then docked into PI3Kα crystal structures to form ligand-receptor complexes, which are further validated by the Glide-XP program to result in structural validated hits. The structural validated hits were examined by PI3Kα inhibitory assay. With this screening protocol, ten PI3Kα inhibitors with new scaffolds were discovered with IC 50 values ranging 0.44-31.25 μM. The binding affinities for the most active compounds 33 and 74 were estimated through molecular dynamics simulations and MM-PBSA analyses.
Yu, Miao; Gu, Qiong; Xu, Jun
2018-02-01
PI3Kα is a promising drug target for cancer chemotherapy. In this paper, we report a strategy of combing ligand-based and structure-based virtual screening to identify new PI3Kα inhibitors. First, naïve Bayesian (NB) learning models and a 3D-QSAR pharmacophore model were built based upon known PI3Kα inhibitors. Then, the SPECS library was screened by the best NB model. This resulted in virtual hits, which were validated by matching the structures against the pharmacophore models. The pharmacophore matched hits were then docked into PI3Kα crystal structures to form ligand-receptor complexes, which are further validated by the Glide-XP program to result in structural validated hits. The structural validated hits were examined by PI3Kα inhibitory assay. With this screening protocol, ten PI3Kα inhibitors with new scaffolds were discovered with IC50 values ranging 0.44-31.25 μM. The binding affinities for the most active compounds 33 and 74 were estimated through molecular dynamics simulations and MM-PBSA analyses.
Pham-The, H; Casañola-Martin, G; Diéguez-Santana, K; Nguyen-Hai, N; Ngoc, N T; Vu-Duc, L; Le-Thi-Thu, H
2017-03-01
Histone deacetylases (HDAC) are emerging as promising targets in cancer, neuronal diseases and immune disorders. Computational modelling approaches have been widely applied for the virtual screening and rational design of novel HDAC inhibitors. In this study, different machine learning (ML) techniques were applied for the development of models that accurately discriminate HDAC2 inhibitors form non-inhibitors. The obtained models showed encouraging results, with the global accuracy in the external set ranging from 0.83 to 0.90. Various aspects related to the comparison of modelling techniques, applicability domain and descriptor interpretations were discussed. Finally, consensus predictions of these models were used for screening HDAC2 inhibitors from four chemical libraries whose bioactivities against HDAC1, HDAC3, HDAC6 and HDAC8 have been known. According to the results of virtual screening assays, structures of some hits with pair-isoform-selective activity (between HDAC2 and other HDACs) were revealed. This study illustrates the power of ML-based QSAR approaches for the screening and discovery of potent, isoform-selective HDACIs.
The virtual slide in the promotion of cytologic and hystologic quality in oncologic screenings
Directory of Open Access Journals (Sweden)
Arrigo Bondi
2010-06-01
Full Text Available A regional experience environment in virtual microscopy and digital pathology comprehending the digital cytology is presented. The project has been conducted in Emilia-Romagna and it has been planned for the promotion and the quality assessment in screening cytology and histology for the prevention of the tumors of uterine cervix, breast and colon-rectum cancers. During the project it has been envisaged the design of a dedicated picture archive and communication system (PACS for cooperative diagnosis, didactics and training, teleconsulting, documentation of rare cases and pilot experiences; furthermore selected cases are catalogued in the PACS with the aim of the check of the diagnostic concordance in the oncologic screening.
Sense of presence and anxiety during virtual social interactions between a human and virtual humans.
Morina, Nexhmedin; Brinkman, Willem-Paul; Hartanto, Dwi; Emmelkamp, Paul M G
2014-01-01
Virtual reality exposure therapy (VRET) has been shown to be effective in treatment of anxiety disorders. Yet, there is lack of research on the extent to which interaction between the individual and virtual humans can be successfully implanted to increase levels of anxiety for therapeutic purposes. This proof-of-concept pilot study aimed at examining levels of the sense of presence and anxiety during exposure to virtual environments involving social interaction with virtual humans and using different virtual reality displays. A non-clinical sample of 38 participants was randomly assigned to either a head-mounted display (HMD) with motion tracker and sterescopic view condition or a one-screen projection-based virtual reality display condition. Participants in both conditions engaged in free speech dialogues with virtual humans controlled by research assistants. It was hypothesized that exposure to virtual social interactions will elicit moderate levels of sense of presence and anxiety in both groups. Further it was expected that participants in the HMD condition will report higher scores of sense of presence and anxiety than participants in the one-screen projection-based display condition. Results revealed that in both conditions virtual social interactions were associated with moderate levels of sense of presence and anxiety. Additionally, participants in the HMD condition reported significantly higher levels of presence than those in the one-screen projection-based display condition (p = .001). However, contrary to the expectations neither the average level of anxiety nor the highest level of anxiety during exposure to social virtual environments differed between the groups (p = .97 and p = .75, respectively). The findings suggest that virtual social interactions can be successfully applied in VRET to enhance sense of presence and anxiety. Furthermore, our results indicate that one-screen projection-based displays can successfully activate levels of anxiety in
Sense of presence and anxiety during virtual social interactions between a human and virtual humans
Directory of Open Access Journals (Sweden)
Nexhmedin Morina
2014-04-01
Full Text Available Virtual reality exposure therapy (VRET has been shown to be effective in treatment of anxiety disorders. Yet, there is lack of research on the extent to which interaction between the individual and virtual humans can be successfully implanted to increase levels of anxiety for therapeutic purposes. This proof-of-concept pilot study aimed at examining levels of the sense of presence and anxiety during exposure to virtual environments involving social interaction with virtual humans and using different virtual reality displays. A non-clinical sample of 38 participants was randomly assigned to either a head-mounted display (HMD with motion tracker and sterescopic view condition or a one-screen projection-based virtual reality display condition. Participants in both conditions engaged in free speech dialogues with virtual humans controlled by research assistants. It was hypothesized that exposure to virtual social interactions will elicit moderate levels of sense of presence and anxiety in both groups. Further it was expected that participants in the HMD condition will report higher scores of sense of presence and anxiety than participants in the one-screen projection-based display condition. Results revealed that in both conditions virtual social interactions were associated with moderate levels of sense of presence and anxiety. Additionally, participants in the HMD condition reported significantly higher levels of presence than those in the one-screen projection-based display condition (p = .001. However, contrary to the expectations neither the average level of anxiety nor the highest level of anxiety during exposure to social virtual environments differed between the groups (p = .97 and p = .75, respectively. The findings suggest that virtual social interactions can be successfully applied in VRET to enhance sense of presence and anxiety. Furthermore, our results indicate that one-screen projection-based displays can successfully activate levels
Directory of Open Access Journals (Sweden)
Glantz-Gashai Y
2017-06-01
Full Text Available Yitav Glantz-Gashai,* Tomer Meirson,* Eli Reuveni, Abraham O Samson Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel *These authors contributed equally to this work Abstract: Myeloid cell leukemia-1 (Mcl-1 is often overexpressed in human cancer and is an important target for developing antineoplastic drugs. In this study, a data set containing 2.3 million lead-like molecules and a data set of all the US Food and Drug Administration (FDA-approved drugs are virtually screened for potential Mcl-1 ligands using Protein Data Bank (PDB ID 2MHS. The potential Mcl-1 ligands are evaluated and computationally docked on to three conformation ensembles generated by normal mode analysis (NMA, molecular dynamics (MD, and nuclear magnetic resonance (NMR, respectively. The evaluated potential Mcl-1 ligands are then compared with their clinical use. Remarkably, half of the top 30 potential drugs are used clinically to treat cancer, thus partially validating our virtual screen. The partial validation also favors the idea that the other half of the top 30 potential drugs could be used in the treatment of cancer. The normal mode-, MD-, and NMR-based conformation greatly expand the conformational sampling used herein for in silico identification of potential Mcl-1 inhibitors. Keywords: virtual screening, Mcl-1, molecular dynamics, NMR, normal modes
Novel inhibitors to Taenia solium Cu/Zn superoxide dismutase identified by virtual screening
García-Gutiérrez, P.; Landa-Piedra, A.; Rodríguez-Romero, A.; Parra-Unda, R.; Rojo-Domínguez, A.
2011-12-01
We describe in this work a successful virtual screening and experimental testing aimed to the identification of novel inhibitors of superoxide dismutase of the worm Taenia solium ( TsCu/Zn-SOD), a human parasite. Conformers from LeadQuest® database of drug-like compounds were selected and then docked on the surface of TsCu/Zn-SOD. Results were screened looking for ligand contacts with receptor side-chains not conserved in the human homologue, with a subsequent development of a score optimization by a set of energy minimization steps, aimed to identify lead compounds for in vitro experiments. Six out of fifty experimentally tested compounds showed μM inhibitory activity toward TsCu/Zn-SOD. Two of them showed species selectivity since did not inhibit the homologous human enzyme when assayed in vitro.
Directory of Open Access Journals (Sweden)
Chiara Ruggeri
Full Text Available The Plasmodium falciparum PfA-M1 and PfA-M17 metalloaminopeptidases are validated drug targets for the discovery of antimalarial agents. In order to identify dual inhibitors of both proteins, we developed a hierarchical virtual screening approach, followed by in vitro evaluation of the highest scoring hits. Starting from the ZINC database of purchasable compounds, sequential 3D-pharmacophore and molecular docking steps were applied to filter the virtual 'hits'. At the end of virtual screening, 12 compounds were chosen and tested against the in vitro aminopeptidase activity of both PfA-M1 and PfA-M17. Two molecules showed significant inhibitory activity (low micromolar/nanomolar range against both proteins. Finally, the crystal structure of the most potent compound in complex with both PfA-M1 and PfA-M17 was solved, revealing the binding mode and validating our computational approach.
Virtual screening for HIV protease inhibitors: a comparison of AutoDock 4 and Vina.
Directory of Open Access Journals (Sweden)
Max W Chang
Full Text Available BACKGROUND: The AutoDock family of software has been widely used in protein-ligand docking research. This study compares AutoDock 4 and AutoDock Vina in the context of virtual screening by using these programs to select compounds active against HIV protease. METHODOLOGY/PRINCIPAL FINDINGS: Both programs were used to rank the members of two chemical libraries, each containing experimentally verified binders to HIV protease. In the case of the NCI Diversity Set II, both AutoDock 4 and Vina were able to select active compounds significantly better than random (AUC = 0.69 and 0.68, respectively; p<0.001. The binding energy predictions were highly correlated in this case, with r = 0.63 and iota = 0.82. For a set of larger, more flexible compounds from the Directory of Universal Decoys, the binding energy predictions were not correlated, and only Vina was able to rank compounds significantly better than random. CONCLUSIONS/SIGNIFICANCE: In ranking smaller molecules with few rotatable bonds, AutoDock 4 and Vina were equally capable, though both exhibited a size-related bias in scoring. However, as Vina executes more quickly and is able to more accurately rank larger molecules, researchers should look to it first when undertaking a virtual screen.
Xia, Jie; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren; Wang, Xiang Simon
2014-05-27
Benchmarking data sets have become common in recent years for the purpose of virtual screening, though the main focus had been placed on the structure-based virtual screening (SBVS) approaches. Due to the lack of crystal structures, there is great need for unbiased benchmarking sets to evaluate various ligand-based virtual screening (LBVS) methods for important drug targets such as G protein-coupled receptors (GPCRs). To date these ready-to-apply data sets for LBVS are fairly limited, and the direct usage of benchmarking sets designed for SBVS could bring the biases to the evaluation of LBVS. Herein, we propose an unbiased method to build benchmarking sets for LBVS and validate it on a multitude of GPCRs targets. To be more specific, our methods can (1) ensure chemical diversity of ligands, (2) maintain the physicochemical similarity between ligands and decoys, (3) make the decoys dissimilar in chemical topology to all ligands to avoid false negatives, and (4) maximize spatial random distribution of ligands and decoys. We evaluated the quality of our Unbiased Ligand Set (ULS) and Unbiased Decoy Set (UDS) using three common LBVS approaches, with Leave-One-Out (LOO) Cross-Validation (CV) and a metric of average AUC of the ROC curves. Our method has greatly reduced the "artificial enrichment" and "analogue bias" of a published GPCRs benchmarking set, i.e., GPCR Ligand Library (GLL)/GPCR Decoy Database (GDD). In addition, we addressed an important issue about the ratio of decoys per ligand and found that for a range of 30 to 100 it does not affect the quality of the benchmarking set, so we kept the original ratio of 39 from the GLL/GDD.
Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library.
Ma, Dik-Lung; Chan, Daniel Shiu-Hin; Wei, Guo; Zhong, Hai-Jing; Yang, Hui; Leung, Lai To; Gullen, Elizabeth A; Chiu, Pauline; Cheng, Yung-Chi; Leung, Chung-Hang
2014-11-21
Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.
Sheridan, Robert P
2008-02-01
We introduce two ways of testing the robustness of conclusions from studies comparing virtual screening methods: alternative "global goodness" metrics and sensitivity analysis. While the robustness tests cannot eliminate all biases in virtual screening comparisons, they are useful as a "reality check" for any given study. To illustrate this, we apply them to a set of enrichments published in McGaughey et al. (J. Chem. Inf. Model. 2007, 47, 1504-1519) where 11 target protein/ligand combinations are tested on 2D and 3D similarity methods, plus docking. The major conclusions in that paper, for instance, that ligand-based methods are better than docking methods, hold up. However, some minor conclusions, such as Glide being the best docking method, do not.
Virtual screening for potential inhibitors of bacterial MurC and MurD ligases.
Tomašić, Tihomir; Kovač, Andreja; Klebe, Gerhard; Blanot, Didier; Gobec, Stanislav; Kikelj, Danijel; Mašič, Lucija Peterlin
2012-03-01
Mur ligases are bacterial enzymes involved in the cytoplasmic steps of peptidoglycan biosynthesis and are viable targets for antibacterial drug discovery. We have performed virtual screening for potential ATP-competitive inhibitors targeting MurC and MurD ligases, using a protocol of consecutive hierarchical filters. Selected compounds were evaluated for inhibition of MurC and MurD ligases, and weak inhibitors possessing dual inhibitory activity have been identified. These compounds represent new scaffolds for further optimisation towards multiple Mur ligase inhibitors with improved inhibitory potency.
The U.S. EPA’s ToxCastTM program has screened over a thousand chemicals for potential toxicity using hundreds of high-throughput, in vitro assays. The U.S. EPA’s Virtual Liver (v-Liver™) is a cellular systems model of hepatic tissues that enables the estimation of in vivo effects...
Value of Virtual Colonoscopy with 64 Row CT in Evaluation of Colorectal Cancer
International Nuclear Information System (INIS)
Zaleska-Dorobisz, Urszula; Łasecki, Mateusz; Nienartowicz, Ewa; Pelak, Joanna; Słonina, Joanna; Olchowy, Cyprian; Ścieżka, Marek; Sąsiadek, Marek
2014-01-01
Virtual colonoscopy (VC) enables three-dimensional view of walls and internal lumen of the colon as a result of reconstruction of multislice CT images. The role of VC in diagnosis of the colon abnormalities systematically increases, and in many medical centers all over the world is carried out as a screening test of patients with high risk of colorectal cancer. We analyzed results of virtual colonoscopy of 360 patients with clinical suspicion of colorectal cancer. Sensitivity and specificity of CT colonoscopy for detection of colon cancers and polyps were assessed. Results of our research have shown high diagnostic efficiency of CT colonoscopy in detection of focal lesions in large intestine of 10 mm or more diameter. Sensitivity was 85.7%, specificity 89.2%. Virtual colonoscopy is noninvasive and well tolerated by patients imaging method, which permits for early detection of the large intestine lesions with specificity and sensitivity similar to classical colonoscopy in screening exams in patients suspected for colorectal cancer. Good preparation of the patients for the examination is very important for proper diagnosis and interpretation of this imaginge procedure
Lin, Shih-Hung; Huang, Kao-Jean; Weng, Ching-Feng; Shiuan, David
2015-01-01
Cholesterol plays an important role in living cells. However, a very high level of cholesterol may lead to atherosclerosis. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase is the key enzyme in the cholesterol biosynthesis pathway, and the statin-like drugs are inhibitors of human HMG-CoA reductase (hHMGR). The present study aimed to virtually screen for potential hHMGR inhibitors from natural product to discover hypolipidemic drug candidates with fewer side effects and lesser toxicities. We used the 3D structure 1HWK from the PDB (Protein Data Bank) database of hHMGR as the target to screen for the strongly bound compounds from the traditional Chinese medicine database. Many interesting molecules including polyphenolic compounds, polisubstituted heterocyclics, and linear lipophilic alcohols were identified and their ADMET (absorption, disrtibution, metabolism, excretion, toxicity) properties were predicted. Finally, four compounds were obtained for the in vitro validation experiments. The results indicated that curcumin and salvianolic acid C can effectively inhibit hHMGR, with IC50 (half maximal inhibitory concentration) values of 4.3 µM and 8 µM, respectively. The present study also demonstrated the feasibility of discovering new drug candidates through structure-based virtual screening.
Benchmarking Methods and Data Sets for Ligand Enrichment Assessment in Virtual Screening
Xia, Jie; Tilahun, Ermias Lemma; Reid, Terry-Elinor; Zhang, Liangren; Wang, Xiang Simon
2014-01-01
Retrospective small-scale virtual screening (VS) based on benchmarking data sets has been widely used to estimate ligand enrichments of VS approaches in the prospective (i.e. real-world) efforts. However, the intrinsic differences of benchmarking sets to the real screening chemical libraries can cause biased assessment. Herein, we summarize the history of benchmarking methods as well as data sets and highlight three main types of biases found in benchmarking sets, i.e. “analogue bias”, “artificial enrichment” and “false negative”. In addition, we introduced our recent algorithm to build maximum-unbiased benchmarking sets applicable to both ligand-based and structure-based VS approaches, and its implementations to three important human histone deacetylase (HDAC) isoforms, i.e. HDAC1, HDAC6 and HDAC8. The Leave-One-Out Cross-Validation (LOO CV) demonstrates that the benchmarking sets built by our algorithm are maximum-unbiased in terms of property matching, ROC curves and AUCs. PMID:25481478
Benchmarking methods and data sets for ligand enrichment assessment in virtual screening.
Xia, Jie; Tilahun, Ermias Lemma; Reid, Terry-Elinor; Zhang, Liangren; Wang, Xiang Simon
2015-01-01
Retrospective small-scale virtual screening (VS) based on benchmarking data sets has been widely used to estimate ligand enrichments of VS approaches in the prospective (i.e. real-world) efforts. However, the intrinsic differences of benchmarking sets to the real screening chemical libraries can cause biased assessment. Herein, we summarize the history of benchmarking methods as well as data sets and highlight three main types of biases found in benchmarking sets, i.e. "analogue bias", "artificial enrichment" and "false negative". In addition, we introduce our recent algorithm to build maximum-unbiased benchmarking sets applicable to both ligand-based and structure-based VS approaches, and its implementations to three important human histone deacetylases (HDACs) isoforms, i.e. HDAC1, HDAC6 and HDAC8. The leave-one-out cross-validation (LOO CV) demonstrates that the benchmarking sets built by our algorithm are maximum-unbiased as measured by property matching, ROC curves and AUCs. Copyright © 2014 Elsevier Inc. All rights reserved.
Directory of Open Access Journals (Sweden)
W. A. Gallus Jr.
2006-01-01
Full Text Available A visually realistic tornadic supercell thunderstorm has been constructed in a fully immersive virtual reality environment to allow students to better understand the complex small-scale dynamics present in such a storm through data probing. Less-immersive versions have been created that run on PCs, facilitating broader dissemination. The activity has been tested in introductory meteorology classes over the last four years. An exercise involving the virtual storm was first used by a subset of students from a large introductory meteorology course in spring 2002. Surveys were used at that time to evaluate the impact of this activity as a constructivist learning tool. More recently, data probe capabilities were added to the virtual storm activity enabling students to take measurements of temperature, wind, pressure, relative humidity, and vertical velocity at any point within the 3-D volume of the virtual world, and see the data plotted via a graphical user interface. Similar surveys applied to groups of students in 2003 and 2004 suggest that the addition of data probing improved the understanding of storm-scale features, but the improved understanding may not be statistically significant when evaluated using quizzes reflecting short-term retention. The use of the activity was revised in 2005 to first have students pose scientific questions about these storms and think about a scientific strategy to answer their questions before exploring the storm. Once again, scores on quizzes for students who used the virtual storm activity were slightly better than those of students who were exposed to only a typical lecture, but differences were not statistically significant.
De Simone, Angela; Mancini, Francesca; Cosconati, Sandro; Marinelli, Luciana; La Pietra, Valeria; Novellino, Ettore; Andrisano, Vincenza
2013-01-25
In the present work, a human recombinant BACE1 immobilized enzyme reactor (hrBACE1-IMER) has been applied for the sensitive fast screening of 38 compounds selected through a virtual screening approach. HrBACE1-IMER was inserted into a liquid chromatograph coupled with a fluorescent detector. A fluorogenic peptide substrate (M-2420), containing the β-secretase site of the Swedish mutation of APP, was injected and cleaved in the on-line HPLC-hrBACE1-IMER system, giving rise to the fluorescent product. The compounds of the library were tested for their ability to inhibit BACE1 in the immobilized format and to reduce the area related to the chromatographic peak of the fluorescent enzymatic product. The results were validated in solution by using two different FRET methods. Due to the efficient virtual screening methodology, more than fifty percent of the selected compounds showed a measurable inhibitory activity. One of the most active compound (a bis-indanone derivative) was characterized in terms of IC(50) and K(i) determination on the hrBACE1-IMER. Thus, the hrBACE1-IMER has been confirmed as a valid tool for the throughput screening of different chemical entities with potency lower than 30μM for the fast hits' selection and for mode of action determination. Copyright © 2012 Elsevier B.V. All rights reserved.
Ligand efficiency based approach for efficient virtual screening of compound libraries.
Ke, Yi-Yu; Coumar, Mohane Selvaraj; Shiao, Hui-Yi; Wang, Wen-Chieh; Chen, Chieh-Wen; Song, Jen-Shin; Chen, Chun-Hwa; Lin, Wen-Hsing; Wu, Szu-Huei; Hsu, John T A; Chang, Chung-Ming; Hsieh, Hsing-Pang
2014-08-18
Here we report for the first time the use of fit quality (FQ), a ligand efficiency (LE) based measure for virtual screening (VS) of compound libraries. The LE based VS protocol was used to screen an in-house database of 125,000 compounds to identify aurora kinase A inhibitors. First, 20 known aurora kinase inhibitors were docked to aurora kinase A crystal structure (PDB ID: 2W1C); and the conformations of docked ligand were used to create a pharmacophore (PH) model. The PH model was used to screen the database compounds, and rank (PH rank) them based on the predicted IC50 values. Next, LE_Scale, a weight-dependant LE function, was derived from 294 known aurora kinase inhibitors. Using the fit quality (FQ = LE/LE_Scale) score derived from the LE_Scale function, the database compounds were reranked (PH_FQ rank) and the top 151 (0.12% of database) compounds were assessed for aurora kinase A inhibition biochemically. This VS protocol led to the identification of 7 novel hits, with compound 5 showing aurora kinase A IC50 = 1.29 μM. Furthermore, testing of 5 against a panel of 31 kinase reveals that it is selective toward aurora kinase A & B, with <50% inhibition for other kinases at 10 μM concentrations and is a suitable candidate for further development. Incorporation of FQ score in the VS protocol not only helped identify a novel aurora kinase inhibitor, 5, but also increased the hit rate of the VS protocol by improving the enrichment factor (EF) for FQ based screening (EF = 828), compared to PH based screening (EF = 237) alone. The LE based VS protocol disclosed here could be applied to other targets for hit identification in an efficient manner. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
A graph-based approach to construct target-focused libraries for virtual screening.
Naderi, Misagh; Alvin, Chris; Ding, Yun; Mukhopadhyay, Supratik; Brylinski, Michal
2016-01-01
Due to exorbitant costs of high-throughput screening, many drug discovery projects commonly employ inexpensive virtual screening to support experimental efforts. However, the vast majority of compounds in widely used screening libraries, such as the ZINC database, will have a very low probability to exhibit the desired bioactivity for a given protein. Although combinatorial chemistry methods can be used to augment existing compound libraries with novel drug-like compounds, the broad chemical space is often too large to be explored. Consequently, the trend in library design has shifted to produce screening collections specifically tailored to modulate the function of a particular target or a protein family. Assuming that organic compounds are composed of sets of rigid fragments connected by flexible linkers, a molecule can be decomposed into its building blocks tracking their atomic connectivity. On this account, we developed eSynth, an exhaustive graph-based search algorithm to computationally synthesize new compounds by reconnecting these building blocks following their connectivity patterns. We conducted a series of benchmarking calculations against the Directory of Useful Decoys, Enhanced database. First, in a self-benchmarking test, the correctness of the algorithm is validated with the objective to recover a molecule from its building blocks. Encouragingly, eSynth can efficiently rebuild more than 80 % of active molecules from their fragment components. Next, the capability to discover novel scaffolds is assessed in a cross-benchmarking test, where eSynth successfully reconstructed 40 % of the target molecules using fragments extracted from chemically distinct compounds. Despite an enormous chemical space to be explored, eSynth is computationally efficient; half of the molecules are rebuilt in less than a second, whereas 90 % take only about a minute to be generated. eSynth can successfully reconstruct chemically feasible molecules from molecular fragments
DEFF Research Database (Denmark)
Henriksen, Knud; Sporring, Jon; Hornbæk, Kasper
2004-01-01
reviews and provides a mathematical foundation for virtual trackballs. The first, but still popular, virtual trackball was described by Chen et al. [CHECK END OF SENTENCE]. We show that the virtual trackball by Chen et al. does not rotate the object along the intended great circular arc on the virtual...... trackball and we give a correction. Another popular virtual trackball is Shoemake's quaternion implementation [CHECK END OF SENTENCE], which we show to be a special case of the virtual trackball by Chen et al.. Shoemake extends the scope of the virtual trackball to the full screen. Unfortunately, Shoemake......'s virtual trackball is inhomogeneous and discontinuous with consequences for usability. Finally, we review Bell's virtual trackball [CHECK END OF SENTENCE] and discuss studies of the usability of virtual trackballs....
The high throughput virtual slit enables compact, inexpensive Raman spectral imagers
Gooding, Edward; Deutsch, Erik R.; Huehnerhoff, Joseph; Hajian, Arsen R.
2018-02-01
Raman spectral imaging is increasingly becoming the tool of choice for field-based applications such as threat, narcotics and hazmat detection; air, soil and water quality monitoring; and material ID. Conventional fiber-coupled point source Raman spectrometers effectively interrogate a small sample area and identify bulk samples via spectral library matching. However, these devices are very slow at mapping over macroscopic areas. In addition, the spatial averaging performed by instruments that collect binned spectra, particularly when used in combination with orbital raster scanning, tends to dilute the spectra of trace particles in a mixture. Our design, employing free space line illumination combined with area imaging, reveals both the spectral and spatial content of heterogeneous mixtures. This approach is well suited to applications such as detecting explosives and narcotics trace particle detection in fingerprints. The patented High Throughput Virtual Slit1 is an innovative optical design that enables compact, inexpensive handheld Raman spectral imagers. HTVS-based instruments achieve significantly higher spectral resolution than can be obtained with conventional designs of the same size. Alternatively, they can be used to build instruments with comparable resolution to large spectrometers, but substantially smaller size, weight and unit cost, all while maintaining high sensitivity. When used in combination with laser line imaging, this design eliminates sample photobleaching and unwanted photochemistry while greatly enhancing mapping speed, all with high selectivity and sensitivity. We will present spectral image data and discuss applications that are made possible by low cost HTVS-enabled instruments.
Giordano, Assunta; Forte, Giovanni; Massimo, Luigia; Riccio, Raffaele; Bifulco, Giuseppe; Di Micco, Simone
2018-04-12
Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for. Trifluoromethyl-benzenesulfonamides 3-21 were repositioned by means of IVS identifying new lead compounds (14-16, 19 and 20) for the inhibition of erbB4 in the low micromolar range. Among these, compound 20 exhibited an interesting value of IC 50 on MCF7 cell lines, thus validating IVS in lead repurposing. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Virtual Worlds for Virtual Organizing
Rhoten, Diana; Lutters, Wayne
The members and resources of a virtual organization are dispersed across time and space, yet they function as a coherent entity through the use of technologies, networks, and alliances. As virtual organizations proliferate and become increasingly important in society, many may exploit the technical architecture s of virtual worlds, which are the confluence of computer-mediated communication, telepresence, and virtual reality originally created for gaming. A brief socio-technical history describes their early origins and the waves of progress followed by stasis that brought us to the current period of renewed enthusiasm. Examination of contemporary examples demonstrates how three genres of virtual worlds have enabled new arenas for virtual organizing: developer-defined closed worlds, user-modifiable quasi-open worlds, and user-generated open worlds. Among expected future trends are an increase in collaboration born virtually rather than imported from existing organizations, a tension between high-fidelity recreations of the physical world and hyper-stylized imaginations of fantasy worlds, and the growth of specialized worlds optimized for particular sectors, companies, or cultures.
Periwal, Vinita; Scaria, Vinod
2017-01-01
The ubiquitous role of microRNAs (miRNAs) in a number of pathological processes has suggested that they could act as potential drug targets. RNA-binding small molecules offer an attractive means for modulating miRNA function. The availability of bioassay data sets for a variety of biological assays and molecules in public domain provides a new opportunity toward utilizing them to create models and further utilize them for in silico virtual screening approaches to prioritize or assign potential functions for small molecules. Here, we describe a computational strategy based on machine learning for creation of predictive models from high-throughput biological screens for virtual screening of small molecules with the potential to inhibit microRNAs. Such models could be potentially used for computational prioritization of small molecules before performing high-throughput biological assay.
Directory of Open Access Journals (Sweden)
Mantsyzov AB
2012-09-01
Full Text Available Alexey B Mantsyzov,1 Guillaume Bouvier,2 Nathalie Evrard-Todeschi,1 Gildas Bertho11Université Paris Descartes, Sorbonne, Paris, France; 2Institut Pasteur, Paris, FranceAbstract: Evaluation of docking results is one of the most important problems for virtual screening and in silico drug design. Modern approaches for the identification of active compounds in a large data set of docked molecules use energy scoring functions. One of the general and most significant limitations of these methods relates to inaccurate binding energy estimation, which results in false scoring of docked compounds. Automatic analysis of poses using self-organizing maps (AuPosSOM represents an alternative approach for the evaluation of docking results based on the clustering of compounds by the similarity of their contacts with the receptor. A scoring function was developed for the identification of the active compounds in the AuPosSOM clustered dataset. In addition, the AuPosSOM efficiency for the clustering of compounds and the identification of key contacts considered as important for its activity, were also improved. Benchmark tests for several targets revealed that together with the developed scoring function, AuPosSOM represents a good alternative to the energy-based scoring functions for the evaluation of docking results.Keywords: scoring, docking, virtual screening, CAR, AuPosSOM
Discovery of selective inhibitors against EBNA1 via high throughput in silico virtual screening.
Directory of Open Access Journals (Sweden)
Ning Li
2010-04-01
Full Text Available Epstein-Barr Virus (EBV latent infection is associated with several human malignancies and is a causal agent of lymphoproliferative diseases during immunosuppression. While inhibitors of herpesvirus DNA polymerases, like gancyclovir, reduce EBV lytic cycle infection, these treatments have limited efficacy for treating latent infection. EBNA1 is an EBV-encoded DNA-binding protein required for viral genome maintenance during latent infection.Here, we report the identification of a new class of small molecules that inhibit EBNA1 DNA binding activity. These compounds were identified by virtual screening of 90,000 low molecular mass compounds using computational docking programs with the solved crystal structure of EBNA1. Four structurally related compounds were found to inhibit EBNA1-DNA binding in biochemical assays with purified EBNA1 protein. Compounds had a range of 20-100 microM inhibition of EBNA1 in fluorescence polarization assays and were further validated for inhibition using electrophoresis mobility shift assays. These compounds exhibited no significant inhibition of an unrelated DNA binding protein. Three of these compounds inhibited EBNA1 transcription activation function in cell-based assays and reduced EBV genome copy number when incubated with a Burkitt lymphoma cell line.These experiments provide a proof-of-principle that virtual screening can be used to identify specific inhibitors of EBNA1 that may have potential for treatment of EBV latent infection.
Nesaratnam, N; Thomas, P; Vivian, A
2017-10-01
IntroductionDissociated tests of strabismus provide valuable information for diagnosis and monitoring of ocular misalignment in patients with normal retinal correspondence. However, they are vulnerable to operator error and rely on a fixed head position. Virtual reality headsets obviate the need for head fixation, while providing other clear theoretical advantages, including complete control over the illumination and targets presented for the patient's interaction.PurposeWe compared the performance of a virtual reality-based test of ocular misalignment to that of the traditional Lees screen, to establish the feasibility of using virtual reality technology in ophthalmic settings in the future.MethodsThree patients underwent a traditional Lees screen test, and a virtual reality headset-based test of ocular motility. The virtual reality headset-based programme consisted of an initial test to measure horizontal and vertical deviation, followed by a test for torsion.ResultsThe pattern of deviation obtained using the virtual reality-based test showed agreement with that obtained from the Lees screen for patients with a fourth nerve palsy, comitant esotropia, and restrictive thyroid eye disease.ConclusionsThis study reports the first use of a virtual reality headset in assessing ocular misalignment, and demonstrates that it is a feasible dissociative test of strabismus.
Chaput, Ludovic; Martinez-Sanz, Juan; Saettel, Nicolas; Mouawad, Liliane
2016-01-01
In a structure-based virtual screening, the choice of the docking program is essential for the success of a hit identification. Benchmarks are meant to help in guiding this choice, especially when undertaken on a large variety of protein targets. Here, the performance of four popular virtual screening programs, Gold, Glide, Surflex and FlexX, is compared using the Directory of Useful Decoys-Enhanced database (DUD-E), which includes 102 targets with an average of 224 ligands per target and 50 decoys per ligand, generated to avoid biases in the benchmarking. Then, a relationship between these program performances and the properties of the targets or the small molecules was investigated. The comparison was based on two metrics, with three different parameters each. The BEDROC scores with α = 80.5, indicated that, on the overall database, Glide succeeded (score > 0.5) for 30 targets, Gold for 27, FlexX for 14 and Surflex for 11. The performance did not depend on the hydrophobicity nor the openness of the protein cavities, neither on the families to which the proteins belong. However, despite the care in the construction of the DUD-E database, the small differences that remain between the actives and the decoys likely explain the successes of Gold, Surflex and FlexX. Moreover, the similarity between the actives of a target and its crystal structure ligand seems to be at the basis of the good performance of Glide. When all targets with significant biases are removed from the benchmarking, a subset of 47 targets remains, for which Glide succeeded for only 5 targets, Gold for 4 and FlexX and Surflex for 2. The performance dramatic drop of all four programs when the biases are removed shows that we should beware of virtual screening benchmarks, because good performances may be due to wrong reasons. Therefore, benchmarking would hardly provide guidelines for virtual screening experiments, despite the tendency that is maintained, i.e., Glide and Gold display better
LASSO-ligand activity by surface similarity order: a new tool for ligand based virtual screening.
Reid, Darryl; Sadjad, Bashir S; Zsoldos, Zsolt; Simon, Aniko
2008-01-01
Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.
LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening
Reid, Darryl; Sadjad, Bashir S.; Zsoldos, Zsolt; Simon, Aniko
2008-06-01
Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.
Manoharan, Prabu; Ghoshal, Nanda
2018-05-01
Traditional structure-based virtual screening method to identify drug-like small molecules for BACE1 is so far unsuccessful. Location of BACE1, poor Blood Brain Barrier permeability and P-glycoprotein (Pgp) susceptibility of the inhibitors make it even more difficult. Fragment-based drug design method is suitable for efficient optimization of initial hit molecules for target like BACE1. We have developed a fragment-based virtual screening approach to identify/optimize the fragment molecules as a starting point. This method combines the shape, electrostatic, and pharmacophoric features of known fragment molecules, bound to protein conjugate crystal structure, and aims to identify both chemically and energetically feasible small fragment ligands that bind to BACE1 active site. The two top-ranked fragment hits were subjected for a 53 ns MD simulation. Principle component analysis and free energy landscape analysis reveal that the new ligands show the characteristic features of established BACE1 inhibitors. The potent method employed in this study may serve for the development of potential lead molecules for BACE1-directed Alzheimer's disease therapeutics.
Schuster, Daniela; Nashev, Lyubomir G; Kirchmair, Johannes; Laggner, Christian; Wolber, Gerhard; Langer, Thierry; Odermatt, Alex
2008-07-24
17Beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) plays a pivotal role in the local synthesis of the most potent estrogen estradiol. Its expression is a prognostic marker for the outcome of patients with breast cancer and inhibition of 17beta-HSD1 is currently under consideration for breast cancer prevention and treatment. We aimed to identify nonsteroidal 17beta-HSD1 inhibitor scaffolds by virtual screening with pharmacophore models built from crystal structures containing steroidal compounds. The most promising model was validated by comparing predicted and experimentally determined inhibitory activities of several flavonoids. Subsequently, a virtual library of nonsteroidal compounds was screened against the 3D pharmacophore. Analysis of 14 selected compounds yielded four that inhibited the activity of human 17beta-HSD1 (IC 50 below 50 microM). Specificity assessment of identified 17beta-HSD1 inhibitors emphasized the importance of including related short-chain dehydrogenase/reductase (SDR) members to analyze off-target effects. Compound 29 displayed at least 10-fold selectivity over the related SDR enzymes tested.
Discovery of novel SERCA inhibitors by virtual screening of a large compound library.
Elam, Christopher; Lape, Michael; Deye, Joel; Zultowsky, Jodie; Stanton, David T; Paula, Stefan
2011-05-01
Two screening protocols based on recursive partitioning and computational ligand docking methodologies, respectively, were employed for virtual screens of a compound library with 345,000 entries for novel inhibitors of the enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA), a potential target for cancer chemotherapy. A total of 72 compounds that were predicted to be potential inhibitors of SERCA were tested in bioassays and 17 displayed inhibitory potencies at concentrations below 100 μM. The majority of these inhibitors were composed of two phenyl rings tethered to each other by a short link of one to three atoms. Putative interactions between SERCA and the inhibitors were identified by inspection of docking-predicted poses and some of the structural features required for effective SERCA inhibition were determined by analysis of the classification pattern employed by the recursive partitioning models. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Directory of Open Access Journals (Sweden)
Sehrish Iftikhar
2017-11-01
Full Text Available Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against A. solani. We employed computational methodologies to design new SDH inhibitors using homology modeling; pharmacophore modeling and structure based virtual screening. The three dimensional SDH model showed good stereo-chemical and structural properties. Based on virtual screening results twelve commercially available compounds were purchased and tested in vitro and in vivo. The compounds were found to inhibit mycelial growth of A. solani. Moreover in vitro trials showed that inhibitory effects were enhanced with increase in concentrations. Similarly increased disease control was observed in pre-treated potato tubers. Hence the applied in silico strategy led us to identify novel fungicides.
Biedermann, Alexander
2014-01-01
Alexander Biedermann presents a generic hardware-based virtualization approach, which may transform an array of any off-the-shelf embedded processors into a multi-processor system with high execution dynamism. Based on this approach, he highlights concepts for the design of energy aware systems, self-healing systems as well as parallelized systems. For the latter, the novel so-called Agile Processing scheme is introduced by the author, which enables a seamless transition between sequential and parallel execution schemes. The design of such virtualizable systems is further aided by introduction
Roy, Kunal; Mitra, Indrani
2011-07-01
Quantitative structure-activity relationships (QSARs) have important applications in drug discovery research, environmental fate modeling, property prediction, etc. Validation has been recognized as a very important step for QSAR model development. As one of the important objectives of QSAR modeling is to predict activity/property/toxicity of new chemicals falling within the domain of applicability of the developed models and QSARs are being used for regulatory decisions, checking reliability of the models and confidence of their predictions is a very important aspect, which can be judged during the validation process. One prime application of a statistically significant QSAR model is virtual screening for molecules with improved potency based on the pharmacophoric features and the descriptors appearing in the QSAR model. Validated QSAR models may also be utilized for design of focused libraries which may be subsequently screened for the selection of hits. The present review focuses on various metrics used for validation of predictive QSAR models together with an overview of the application of QSAR models in the fields of virtual screening and focused library design for diverse series of compounds with citation of some recent examples.
Moyer-Packenham, Patricia S.; Bullock, Emma K.; Shumway, Jessica F.; Tucker, Stephen I.; Watts, Christina M.; Westenskow, Arla; Anderson-Pence, Katie L.; Maahs-Fladung, Cathy; Boyer-Thurgood, Jennifer; Gulkilik, Hilal; Jordan, Kerry
2016-01-01
This paper focuses on understanding the role that affordances played in children's learning performance and efficiency during clinical interviews of their interactions with mathematics apps on touch-screen devices. One hundred children, ages 3 to 8, each used six different virtual manipulative mathematics apps during 30-40-min interviews. The…
The influence of negative training set size on machine learning-based virtual screening.
Kurczab, Rafał; Smusz, Sabina; Bojarski, Andrzej J
2014-01-01
The paper presents a thorough analysis of the influence of the number of negative training examples on the performance of machine learning methods. The impact of this rather neglected aspect of machine learning methods application was examined for sets containing a fixed number of positive and a varying number of negative examples randomly selected from the ZINC database. An increase in the ratio of positive to negative training instances was found to greatly influence most of the investigated evaluating parameters of ML methods in simulated virtual screening experiments. In a majority of cases, substantial increases in precision and MCC were observed in conjunction with some decreases in hit recall. The analysis of dynamics of those variations let us recommend an optimal composition of training data. The study was performed on several protein targets, 5 machine learning algorithms (SMO, Naïve Bayes, Ibk, J48 and Random Forest) and 2 types of molecular fingerprints (MACCS and CDK FP). The most effective classification was provided by the combination of CDK FP with SMO or Random Forest algorithms. The Naïve Bayes models appeared to be hardly sensitive to changes in the number of negative instances in the training set. In conclusion, the ratio of positive to negative training instances should be taken into account during the preparation of machine learning experiments, as it might significantly influence the performance of particular classifier. What is more, the optimization of negative training set size can be applied as a boosting-like approach in machine learning-based virtual screening.
Evaluating the predictivity of virtual screening for ABL kinase inhibitors to hinder drug resistance
DEFF Research Database (Denmark)
Gani, Osman A B S M; Narayanan, Dilip; Engh, Richard A
2013-01-01
decoy sets and tested with virtual screening approaches with and without explicit use of target structures (docking). We show how various scoring functions and choice of inactive ligand sets influence overall and early enrichment of the libraries. Although ligand-based methods, for example principal...... component analyses of chemical properties, can distinguish some decoy sets from active compounds, the addition of target structural information via docking improves enrichment, and explicit consideration of multiple target conformations (i.e. types I and II) achieves best enrichment of active versus...
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Chen C
2014-09-01
Full Text Available Can Chen,1,2,* Ting Wang,1,3,* Fengbo Wu,1,* Wei Huang,4 Gu He,1 Liang Ouyang,1 Mingli Xiang,1 Cheng Peng,4 Qinglin Jiang1,2 1State Key Laboratory of Biotherapy and Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 2College of Pharmacy and the First Affiliated Hospital, Chengdu Medical College, Chengdu, 3Department of Cardiology, Genenal Hospital of Chengdu Military Command, Chengdu, 4State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workAbstract: Compared with normal differentiated cells, cancer cells upregulate the expression of pyruvate kinase isozyme M2 (PKM2 to support glycolytic intermediates for anabolic processes, including the synthesis of nucleic acids, amino acids, and lipids. In this study, a combination of the structure-based pharmacophore modeling and a hybrid protocol of virtual screening methods comprised of pharmacophore model-based virtual screening, docking-based virtual screening, and in silico ADMET (absorption, distribution, metabolism, excretion and toxicity analysis were used to retrieve novel PKM2 activators from commercially available chemical databases. Tetrahydroquinoline derivatives were identified as potential scaffolds of PKM2 activators. Thus, the hybrid virtual screening approach was applied to screen the focused tetrahydroquinoline derivatives embedded in the ZINC database. Six hit compounds were selected from the final hits and experimental studies were then performed. Compound 8 displayed a potent inhibitory effect on human lung cancer cells. Following treatment with Compound 8, cell viability, apoptosis, and reactive oxygen species (ROS production were examined in A549 cells. Finally, we evaluated the effects of Compound 8 on mice xenograft tumor models in vivo. These results may provide important
Directory of Open Access Journals (Sweden)
Qifeng Bai
Full Text Available We designed a program called MolGridCal that can be used to screen small molecule database in grid computing on basis of JPPF grid environment. Based on MolGridCal program, we proposed an integrated strategy for virtual screening and binding mode investigation by combining molecular docking, molecular dynamics (MD simulations and free energy calculations. To test the effectiveness of MolGridCal, we screened potential ligands for β2 adrenergic receptor (β2AR from a database containing 50,000 small molecules. MolGridCal can not only send tasks to the grid server automatically, but also can distribute tasks using the screensaver function. As for the results of virtual screening, the known agonist BI-167107 of β2AR is ranked among the top 2% of the screened candidates, indicating MolGridCal program can give reasonable results. To further study the binding mode and refine the results of MolGridCal, more accurate docking and scoring methods are used to estimate the binding affinity for the top three molecules (agonist BI-167107, neutral antagonist alprenolol and inverse agonist ICI 118,551. The results indicate agonist BI-167107 has the best binding affinity. MD simulation and free energy calculation are employed to investigate the dynamic interaction mechanism between the ligands and β2AR. The results show that the agonist BI-167107 also has the lowest binding free energy. This study can provide a new way to perform virtual screening effectively through integrating molecular docking based on grid computing, MD simulations and free energy calculations. The source codes of MolGridCal are freely available at http://molgridcal.codeplex.com.
Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu
2015-07-27
Virtual screening methods are commonly used nowadays in drug discovery processes. However, to ensure their reliability, they have to be carefully evaluated. The evaluation of these methods is often realized in a retrospective way, notably by studying the enrichment of benchmarking data sets. To this purpose, numerous benchmarking data sets were developed over the years, and the resulting improvements led to the availability of high quality benchmarking data sets. However, some points still have to be considered in the selection of the active compounds, decoys, and protein structures to obtain optimal benchmarking data sets.
Discovery of novel EGFR tyrosine kinase inhibitors by structure-based virtual screening.
Li, Siyuan; Sun, Xianqiang; Zhao, Hongli; Tang, Yun; Lan, Minbo
2012-06-15
By using of structure-based virtual screening, 13 novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were discovered from 197,116 compounds in the SPECS database here. Among them, 8 compounds significantly inhibited EGFR kinase activity with IC(50) values lower than 10 μM. 3-{[1-(3-Chloro-4-fluorophenyl)-3,5-dioxo-4-pyrazolidinylidene]methyl}phenyl 2-thiophenecarboxylate (13), particularly, was the most potent inhibitor possessing the IC(50) value of 3.5 μM. The docking studies also provide some useful information that the docking models of the 13 compounds are beneficial to find a new path for designing novel EGFR inhibitors. Copyright © 2012 Elsevier Ltd. All rights reserved.
ILP-2 modeling and virtual screening of an FDA-approved library:a possible anticancer therapy.
Khalili, Saeed; Mohammadpour, Hemn; Shokrollahi Barough, Mahideh; Kokhaei, Parviz
2016-06-23
The members of the inhibitors of apoptosis protein (IAP) family inhibit diverse components of the caspase signaling pathway, notably caspase 3, 7, and 9. ILP-2 (BIRC-8) is the most recently identified member of the IAPs, mainly interacting with caspase 9. This interaction would eventually lead to death resistance in the case of cancerous cells. Therefore, structural modeling of ILP-2 and finding applicable inhibitors of its interaction with caspase 9 are a compelling challenge. Three main protein modeling approaches along with various model refinement measures were harnessed to achieve a reliable 3D model, using state-of-the-art software. Thereafter, the selected model was employed to perform virtual screening of an FDA approved library. A model built by a combinatorial approach (homology and ab initio approaches) was chosen as the best model. Model refinement processes successfully bolstered the model quality. Virtual screening of the compound library introduced several high affinity inhibitor candidates that interact with functional residues of ILP2. Given the 3D structure of the ILP2 molecule, we found promising inhibitory molecules. In addition to high affinity towards the ILP2 molecule, these molecules interact with residues that play pivotal rules in ILP2-caspase interaction. These molecules would inhibit ILP2-caspase interaction and consequently would lead to reactivated cell apoptosis through the caspases pathway.
Virtual Reality: Principles and Applications
MÉRIENNE , Frédéric
2017-01-01
Virtual reality aims at immersing a user in a virtual environment. Dedicated virtual reality technologies of human–computer interaction enable to make the link between the user and a virtual environment in capturing the user’s motion, acting on his senses as well as computing the virtual experience in real-time. The immersion in virtual environment is evaluated through the user’s perception and reaction. Virtual reality is used in a large variety of application domains which need multisensory...
Männel, Barbara; Jaiteh, Mariama; Zeifman, Alexey; Randakova, Alena; Möller, Dorothee; Hübner, Harald; Gmeiner, Peter; Carlsson, Jens
2017-10-20
Functionally selective ligands stabilize conformations of G protein-coupled receptors (GPCRs) that induce a preference for signaling via a subset of the intracellular pathways activated by the endogenous agonists. The possibility to fine-tune the functional activity of a receptor provides opportunities to develop drugs that selectively signal via pathways associated with a therapeutic effect and avoid those causing side effects. Animal studies have indicated that ligands displaying functional selectivity at the D 2 dopamine receptor (D 2 R) could be safer and more efficacious drugs against neuropsychiatric diseases. In this work, computational design of functionally selective D 2 R ligands was explored using structure-based virtual screening. Molecular docking of known functionally selective ligands to a D 2 R homology model indicated that such compounds were anchored by interactions with the orthosteric site and extended into a common secondary pocket. A tailored virtual library with close to 13 000 compounds bearing 2,3-dichlorophenylpiperazine, a privileged orthosteric scaffold, connected to diverse chemical moieties via a linker was docked to the D 2 R model. Eighteen top-ranked compounds that occupied both the orthosteric and allosteric site were synthesized, leading to the discovery of 16 partial agonists. A majority of the ligands had comparable maximum effects in the G protein and β-arrestin recruitment assays, but a subset displayed preference for a single pathway. In particular, compound 4 stimulated β-arrestin recruitment (EC 50 = 320 nM, E max = 16%) but had no detectable G protein signaling. The use of structure-based screening and virtual libraries to discover GPCR ligands with tailored functional properties will be discussed.
Moysey, S. M.; Smith, E.; Sellers, V.; Wyant, P.; Boyer, D. M.; Mobley, C.; Brame, S.
2015-12-01
Although field experiences are an important aspect of geoscience education, the opportunity to provide physical world experiences to large groups of introductory students is often limited by access, logistical, and financial constraints. Our project (NSF IUSE 1504619) is investigating the use of immersive virtual reality (VR) technologies as a surrogate for real field experiences in introductory geosciences classes. We are developing a toolbox that leverages innovations in the field of VR, including the Oculus Rift and Google Cardboard, to enable every student in an introductory geology classroom the opportunity to have a first-person virtual field experience in the Grand Canyon. We have opted to structure our VR experience as an interactive game where students must explore the Canyon to accomplish a series of tasks designed to emphasize key aspects of geoscience learning. So far we have produced two demo products for the virtual field trip. The first is a standalone "Rock Box" app developed for the iPhone, which allows students to select different rock samples, examine them in 3D, and obtain basic information about the properties of each sample. The app can act as a supplement to the traditional rock box used in physical geology labs. The second product is a fully functioning VR environment for the Grand Canyon developed using satellite-based topographic and imagery data to retain real geologic features within the experience. Players can freely navigate to explore anywhere they desire within the Canyon, but are guided to points of interest where they are able to complete exercises that will be aligned with specific learning goals. To this point we have integrated elements of the "Rock Box" app within the VR environment, allowing players to examine 3D details of rock samples they encounter within the Grand Canyon. We plan to provide demos of both products and obtain user feedback during our presentation.
Lescinsky, D. T.; Wyborn, L. A.; Evans, B. J. K.; Allen, C.; Fraser, R.; Rankine, T.
2014-12-01
We present collaborative work on a generic, modular infrastructure for virtual laboratories (VLs, similar to science gateways) that combine online access to data, scientific code, and computing resources as services that support multiple data intensive scientific computing needs across a wide range of science disciplines. We are leveraging access to 10+ PB of earth science data on Lustre filesystems at Australia's National Computational Infrastructure (NCI) Research Data Storage Infrastructure (RDSI) node, co-located with NCI's 1.2 PFlop Raijin supercomputer and a 3000 CPU core research cloud. The development, maintenance and sustainability of VLs is best accomplished through modularisation and standardisation of interfaces between components. Our approach has been to break up tightly-coupled, specialised application packages into modules, with identified best techniques and algorithms repackaged either as data services or scientific tools that are accessible across domains. The data services can be used to manipulate, visualise and transform multiple data types whilst the scientific tools can be used in concert with multiple scientific codes. We are currently designing a scalable generic infrastructure that will handle scientific code as modularised services and thereby enable the rapid/easy deployment of new codes or versions of codes. The goal is to build open source libraries/collections of scientific tools, scripts and modelling codes that can be combined in specially designed deployments. Additional services in development include: provenance, publication of results, monitoring, workflow tools, etc. The generic VL infrastructure will be hosted at NCI, but can access alternative computing infrastructures (i.e., public/private cloud, HPC).The Virtual Geophysics Laboratory (VGL) was developed as a pilot project to demonstrate the underlying technology. This base is now being redesigned and generalised to develop a Virtual Hazards Impact and Risk Laboratory
Virtualization A Manager's Guide
Kusnetzky, Dan
2011-01-01
What exactly is virtualization? As this concise book explains, virtualization is a smorgasbord of technologies that offer organizations many advantages, whether you're managing extremely large stores of rapidly changing data, scaling out an application, or harnessing huge amounts of computational power. With this guide, you get an overview of the five main types of virtualization technology, along with information on security, management, and modern use cases. Topics include: Access virtualization-Allows access to any application from any deviceApplication virtualization-Enables applications
Optical methods for enabling focus cues in head-mounted displays for virtual and augmented reality
Hua, Hong
2017-05-01
Developing head-mounted displays (HMD) that offer uncompromised optical pathways to both digital and physical worlds without encumbrance and discomfort confronts many grand challenges, both from technological perspectives and human factors. Among the many challenges, minimizing visual discomfort is one of the key obstacles. One of the key contributing factors to visual discomfort is the lack of the ability to render proper focus cues in HMDs to stimulate natural eye accommodation responses, which leads to the well-known accommodation-convergence cue discrepancy problem. In this paper, I will provide a summary on the various optical methods approaches toward enabling focus cues in HMDs for both virtual reality (VR) and augmented reality (AR).
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Florbela Pereira
2014-05-01
Figure 1. The unreported 15 lead antibiotic MNPs and MbNPs from AntiMarin database, using the best Rfs antibiotic model with a probability of being antibiotic greater than or equal to 0.8. Figure 2. The selected 4 lead antitumor MNPs and MbNPs from the AntiMarin database, using the best Rfs antitumor model with a probability of being antitumor greater than or equal to 0.8. The present work corroborates by one side the results of our previous work6 and enables the presentation of a new set of possible lead like bioactive compounds. Additionally, it is shown the usefulness of quantum-chemical descriptors in the discrimination of biological active and inactive compounds. The use of the εHOMO quantum-chemical descriptor in the discrimination of large scale data sets of lead-like or drug-like compounds has never been reported. This approach results in the reduction, in great extent, of the number of compounds used in real screens, and it reinforces the results of our previous work. Furthermore, besides the virtual screening, the computational methods can be very useful to build appropriate databases, allowing for effective shortcuts of NP extracts dereplication procedures, which will certainly result in increasing the efficiency of drug discovery.
Two-dimensional combinatorial screening enables the bottom-up design of a microRNA-10b inhibitor.
Velagapudi, Sai Pradeep; Disney, Matthew D
2014-03-21
The RNA motifs that bind guanidinylated kanamycin A (G Kan A) and guanidinylated neomycin B (G Neo B) were identified via two-dimensional combinatorial screening (2DCS). The results of these studies enabled the "bottom-up" design of a small molecule inhibitor of oncogenic microRNA-10b.
Ain, Qurrat Ul; Aleksandrova, Antoniya; Roessler, Florian D; Ballester, Pedro J
2015-01-01
Docking tools to predict whether and how a small molecule binds to a target can be applied if a structural model of such target is available. The reliability of docking depends, however, on the accuracy of the adopted scoring function (SF). Despite intense research over the years, improving the accuracy of SFs for structure-based binding affinity prediction or virtual screening has proven to be a challenging task for any class of method. New SFs based on modern machine-learning regression models, which do not impose a predetermined functional form and thus are able to exploit effectively much larger amounts of experimental data, have recently been introduced. These machine-learning SFs have been shown to outperform a wide range of classical SFs at both binding affinity prediction and virtual screening. The emerging picture from these studies is that the classical approach of using linear regression with a small number of expert-selected structural features can be strongly improved by a machine-learning approach based on nonlinear regression allied with comprehensive data-driven feature selection. Furthermore, the performance of classical SFs does not grow with larger training datasets and hence this performance gap is expected to widen as more training data becomes available in the future. Other topics covered in this review include predicting the reliability of a SF on a particular target class, generating synthetic data to improve predictive performance and modeling guidelines for SF development. WIREs Comput Mol Sci 2015, 5:405-424. doi: 10.1002/wcms.1225 For further resources related to this article, please visit the WIREs website.
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Aman C. Kaushik
2018-02-01
Full Text Available GPR142 (G protein receptor 142 is a novel orphan GPCR (G protein coupled receptor belonging to “Class A” of GPCR family and expressed in β cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling, and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.
Kaushik, Aman C.; Kumar, Sanjay; Wei, Dong Q.; Sahi, Shakti
2018-02-01
GPR142 (G protein receptor 142) is a novel orphan GPCR (G protein coupled receptor) belonging to ‘Class A’ of GPCR family and expressed in beta cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.
Podshivalov, D. D.; Timofeev, V. I.; Sidorov-Biryukov, D. D.; Kuranova, I. P.
2017-05-01
Bacterial phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis (PPAT Mt) is a convenient target protein for the directed search for selective inhibitors as potent antituberculosis drugs. Four compounds suitable for the detailed investigation of their interactions with PPAT Mt were found by virtual screening. The active-site region of the enzyme was chosen as the ligand-binding site. The positions of the ligands found by the docking were refined by molecular dynamics simulation. The nearest environment of the ligands, the positions of which in the active site of the enzyme were found in a computational experiment, was analyzed. The compounds under consideration were shown to directly interact with functionally important active-site amino-acid residues and block access of substrates to the active site. Therefore, these compounds can be used for the design of selective inhibitors of PPAT Mt as potent antituberculosis drugs.
High-throughput quantum chemistry and virtual screening for OLED material components
Halls, Mathew D.; Giesen, David J.; Hughes, Thomas F.; Goldberg, Alexander; Cao, Yixiang
2013-09-01
Computational structure enumeration, analysis using an automated simulation workflow and filtering of large chemical structure libraries to identify lead systems, has become a central paradigm in drug discovery research. Transferring this paradigm to challenges in materials science is now possible due to advances in the speed of computational resources and the efficiency and stability of chemical simulation packages. State-of-the-art software tools that have been developed for drug discovery can be applied to efficiently explore the chemical design space to identify solutions for problems such as organic light-emitting diode material components. In this work, virtual screening for OLED materials based on intrinsic quantum mechanical properties is illustrated. Also, a new approach to more reliably identify candidate systems is introduced that is based on the chemical reaction energetics of defect pathways for OLED materials.
Pharmacophore modeling, virtual screening and molecular docking of ATPase inhibitors of HSP70.
Sangeetha, K; Sasikala, R P; Meena, K S
2017-10-01
Heat shock protein 70 is an effective anticancer target as it influences many signaling pathways. Hence the study investigated the important pharmacophore feature required for ATPase inhibitors of HSP70 by generating a ligand based pharmacophore model followed by virtual based screening and subsequent validation by molecular docking in Discovery studio V4.0. The most extrapolative pharmacophore model (hypotheses 8) consisted of four hydrogen bond acceptors. Further validation by external test set prediction identified 200 hits from Mini Maybridge, Drug Diverse, SCPDB compounds and Phytochemicals. Consequently, the screened compounds were refined by rule of five, ADMET and molecular docking to retain the best competitive hits. Finally Phytochemical compounds Muricatetrocin B, Diacetylphiladelphicalactone C, Eleutheroside B and 5-(3-{[1-(benzylsulfonyl)piperidin-4-yl]amino}phenyl)- 4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid were obtained as leads to inhibit the ATPase activity of HSP70 in our findings and thus can be proposed for further in vitro and in vivo evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Gowthaman, Ragul; Miller, Sven A; Rogers, Steven; Khowsathit, Jittasak; Lan, Lan; Bai, Nan; Johnson, David K; Liu, Chunjing; Xu, Liang; Anbanandam, Asokan; Aubé, Jeffrey; Roy, Anuradha; Karanicolas, John
2016-05-12
Protein-protein interactions represent an exciting and challenging target class for therapeutic intervention using small molecules. Protein interaction sites are often devoid of the deep surface pockets presented by "traditional" drug targets, and crystal structures reveal that inhibitors typically engage these sites using very shallow binding modes. As a consequence, modern virtual screening tools developed to identify inhibitors of traditional drug targets do not perform as well when they are instead deployed at protein interaction sites. To address the need for novel inhibitors of important protein interactions, here we introduce an alternate docking strategy specifically designed for this regime. Our method, termed DARC (Docking Approach using Ray-Casting), matches the topography of a surface pocket "observed" from within the protein to the topography "observed" when viewing a potential ligand from the same vantage point. We applied DARC to carry out a virtual screen against the protein interaction site of human antiapoptotic protein Mcl-1 and found that four of the top-scoring 21 compounds showed clear inhibition in a biochemical assay. The Ki values for these compounds ranged from 1.2 to 21 μM, and each had ligand efficiency comparable to promising small-molecule inhibitors of other protein-protein interactions. These hit compounds do not resemble the natural (protein) binding partner of Mcl-1, nor do they resemble any known inhibitors of Mcl-1. Our results thus demonstrate the utility of DARC for identifying novel inhibitors of protein-protein interactions.
Jasper, Julia B; Humbeck, Lina; Brinkjost, Tobias; Koch, Oliver
2018-03-16
Protein ligand interaction fingerprints are a powerful approach for the analysis and assessment of docking poses to improve docking performance in virtual screening. In this study, a novel interaction fingerprint approach (PADIF, protein per atom score contributions derived interaction fingerprint) is presented which was specifically designed for utilising the GOLD scoring functions' atom contributions together with a specific scoring scheme. This allows the incorporation of known protein-ligand complex structures for a target-specific scoring. Unlike many other methods, this approach uses weighting factors reflecting the relative frequency of a specific interaction in the references and penalizes destabilizing interactions. In addition, and for the first time, an exhaustive validation study was performed that assesses the performance of PADIF and two other interaction fingerprints in virtual screening. Here, PADIF shows superior results, and some rules of thumb for a successful use of interaction fingerprints could be identified.
Anastilosis Virtual de Felipéia
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Hélio Costa Lima
2011-04-01
Full Text Available This text is about a virtual anastylosis of Felipéia, capital of Paraíba, the first city founded in Brazil under the Spanish Crown in 1585, during the Iberic Union. Recently, infographics resources enabled the reconstruction, with great precision, of the old city’s ground plans from Dutch maps from 1634-37, and establish the first hypothesis of a tridimensional configuration of the city. Now, measuring and studies are being done to make possible a piece by piece virtual anastylosis of the buildings and, after that, a tridimensional virtual reconstruction of the historical city, which will enable virtual walkabouts on the streets, squares and buildings.
Lahiani, Amal; Klaiman, Eldad; Grimm, Oliver
2018-01-01
Medical diagnosis and clinical decisions rely heavily on the histopathological evaluation of tissue samples, especially in oncology. Historically, classical histopathology has been the gold standard for tissue evaluation and assessment by pathologists. The most widely and commonly used dyes in histopathology are hematoxylin and eosin (H&E) as most malignancies diagnosis is largely based on this protocol. H&E staining has been used for more than a century to identify tissue characteristics and structures morphologies that are needed for tumor diagnosis. In many cases, as tissue is scarce in clinical studies, fluorescence imaging is necessary to allow staining of the same specimen with multiple biomarkers simultaneously. Since fluorescence imaging is a relatively new technology in the pathology landscape, histopathologists are not used to or trained in annotating or interpreting these images. To allow pathologists to annotate these images without the need for additional training, we designed an algorithm for the conversion of fluorescence images to brightfield H&E images. In this algorithm, we use fluorescent nuclei staining to reproduce the hematoxylin information and natural tissue autofluorescence to reproduce the eosin information avoiding the necessity to specifically stain the proteins or intracellular structures with an additional fluorescence stain. Our method is based on optimizing a transform function from fluorescence to H&E images using least mean square optimization. It results in high quality virtual H&E digital images that can easily and efficiently be analyzed by pathologists. We validated our results with pathologists by making them annotate tumor in real and virtual H&E whole slide images and we obtained promising results. Hence, we provide a solution that enables pathologists to assess tissue and annotate specific structures based on multiplexed fluorescence images.
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Amal Lahiani
2018-01-01
Full Text Available Context: Medical diagnosis and clinical decisions rely heavily on the histopathological evaluation of tissue samples, especially in oncology. Historically, classical histopathology has been the gold standard for tissue evaluation and assessment by pathologists. The most widely and commonly used dyes in histopathology are hematoxylin and eosin (H&E as most malignancies diagnosis is largely based on this protocol. H&E staining has been used for more than a century to identify tissue characteristics and structures morphologies that are needed for tumor diagnosis. In many cases, as tissue is scarce in clinical studies, fluorescence imaging is necessary to allow staining of the same specimen with multiple biomarkers simultaneously. Since fluorescence imaging is a relatively new technology in the pathology landscape, histopathologists are not used to or trained in annotating or interpreting these images. Aims, Settings and Design: To allow pathologists to annotate these images without the need for additional training, we designed an algorithm for the conversion of fluorescence images to brightfield H&E images. Subjects and Methods: In this algorithm, we use fluorescent nuclei staining to reproduce the hematoxylin information and natural tissue autofluorescence to reproduce the eosin information avoiding the necessity to specifically stain the proteins or intracellular structures with an additional fluorescence stain. Statistical Analysis Used: Our method is based on optimizing a transform function from fluorescence to H&E images using least mean square optimization. Results: It results in high quality virtual H&E digital images that can easily and efficiently be analyzed by pathologists. We validated our results with pathologists by making them annotate tumor in real and virtual H&E whole slide images and we obtained promising results. Conclusions: Hence, we provide a solution that enables pathologists to assess tissue and annotate specific structures
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Wang J
2016-12-01
Full Text Available Jing Wang,1,* Chunxia Qiao,1,* He Xiao,1 Zhou Lin,1 Yan Li,1 Jiyan Zhang,1 Beifen Shen,1 Tinghuan Fu,2 Jiannan Feng1 1Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, 2First Affiliated Hospital of PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: According to the three-dimensional (3D complex structure of (hIL-6·hIL-6R·gp 1302 and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD and MDL Drug Data Report (MDDR, by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist. Keywords: virtual screening, structural optimization, human interlukin-6, small molecular antagonist, XG-7 cells, apoptosis
Fragment virtual screening based on Bayesian categorization for discovering novel VEGFR-2 scaffolds.
Zhang, Yanmin; Jiao, Yu; Xiong, Xiao; Liu, Haichun; Ran, Ting; Xu, Jinxing; Lu, Shuai; Xu, Anyang; Pan, Jing; Qiao, Xin; Shi, Zhihao; Lu, Tao; Chen, Yadong
2015-11-01
The discovery of novel scaffolds against a specific target has long been one of the most significant but challengeable goals in discovering lead compounds. A scaffold that binds in important regions of the active pocket is more favorable as a starting point because scaffolds generally possess greater optimization possibilities. However, due to the lack of sufficient chemical space diversity of the databases and the ineffectiveness of the screening methods, it still remains a great challenge to discover novel active scaffolds. Since the strengths and weaknesses of both fragment-based drug design and traditional virtual screening (VS), we proposed a fragment VS concept based on Bayesian categorization for the discovery of novel scaffolds. This work investigated the proposal through an application on VEGFR-2 target. Firstly, scaffold and structural diversity of chemical space for 10 compound databases were explicitly evaluated. Simultaneously, a robust Bayesian classification model was constructed for screening not only compound databases but also their corresponding fragment databases. Although analysis of the scaffold diversity demonstrated a very unevenly distribution of scaffolds over molecules, results showed that our Bayesian model behaved better in screening fragments than molecules. Through a literature retrospective research, several generated fragments with relatively high Bayesian scores indeed exhibit VEGFR-2 biological activity, which strongly proved the effectiveness of fragment VS based on Bayesian categorization models. This investigation of Bayesian-based fragment VS can further emphasize the necessity for enrichment of compound databases employed in lead discovery by amplifying the diversity of databases with novel structures.
Le-Thi-Thu, Huong; Casanola-Martín, Gerardo M; Marrero-Ponce, Yovani; Rescigno, Antonio; Abad, Concepcion; Khan, Mahmud Tareq Hassan
2014-01-01
The tyrosinase is a bifunctional, copper-containing enzyme widely distributed in the phylogenetic tree. This enzyme is involved in the production of melanin and some other pigments in humans, animals and plants, including skin pigmentations in mammals, and browning process in plants and vegetables. Therefore, enzyme inhibitors has been under the attention of the scientist community, due to its broad applications in food, cosmetic, agricultural and medicinal fields, to avoid the undesirable effects of abnormal melanin overproduction. However, the research of novel chemical with antityrosinase activity demands the use of more efficient tools to speed up the tyrosinase inhibitors discovery process. This chapter is focused in the different components of a predictive modeling workflow for the identification and prioritization of potential new compounds with activity against the tyrosinase enzyme. In this case, two structure chemical libraries Spectrum Collection and Drugbank are used in this attempt to combine different virtual screening data mining techniques, in a sequential manner helping to avoid the usually expensive and time consuming traditional methods. Some of the sequential steps summarize here comprise the use of drug-likeness filters, similarity searching, classification and potency QSAR multiclassifier systems, modeling molecular interactions systems, and similarity/diversity analysis. Finally, the methodologies showed here provide a rational workflow for virtual screening hit analysis and selection as a promissory drug discovery strategy for use in target identification phase.
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Singh S
2018-05-01
Full Text Available Swati Singh,1 Garima Khare,1 Ritika Kar Bahal,1 Prahlad C Ghosh,1 Anil K Tyagi1,2 1Department of Biochemistry, University of Delhi South Campus, New Delhi, India; 2Guru Gobind Singh Indraprastha University, New Delhi, India Background: 7,8-Diaminopelargonic acid synthase (BioA, an enzyme of biotin biosynthesis pathway, is a well-known promising target for anti-tubercular drug development. Methods: In this study, structure-based virtual screening was employed against the active site of BioA to identify new chemical entities for BioA inhibition and top ranking compounds were evaluated for their ability to inhibit BioA enzymatic activity. Results: Seven compounds inhibited BioA enzymatic activity by greater than 60% at 100 µg/mL with most potent compounds being A36, A35 and A65, displaying IC50 values of 10.48 µg/mL (28.94 µM, 33.36 µg/mL (88.16 µM and 39.17 µg/mL (114.42 µM, respectively. Compounds A65 and A35 inhibited Mycobacterium tuberculosis (M. tuberculosis growth with MIC90 of 20 µg/mL and 80 µg/mL, respectively, whereas compound A36 exhibited relatively weak inhibition of M. tuberculosis growth (83% inhibition at 200 µg/mL. Compound A65 emerged as the most potent compound identified in our study that inhibited BioA enzymatic activity and growth of the pathogen and possessed drug-like properties. Conclusion: Our study has identified a few hit molecules against M. tuberculosis BioA that can act as potential candidates for further development of potent anti-tubercular therapeutic agents. Keywords: Mycobacterium tuberculosis, BioA, virtual screening, drug discovery
Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors.
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Frederick Daidone
Full Text Available Dopa decarboxylase (DDC, a pyridoxal 5'-phosphate (PLP enzyme responsible for the biosynthesis of dopamine and serotonin, is involved in Parkinson's disease (PD. PD is a neurodegenerative disease mainly due to a progressive loss of dopamine-producing cells in the midbrain. Co-administration of L-Dopa with peripheral DDC inhibitors (carbidopa or benserazide is the most effective symptomatic treatment for PD. Although carbidopa and trihydroxybenzylhydrazine (the in vivo hydrolysis product of benserazide are both powerful irreversible DDC inhibitors, they are not selective because they irreversibly bind to free PLP and PLP-enzymes, thus inducing diverse side effects. Therefore, the main goals of this study were (a to use virtual screening to identify potential human DDC inhibitors and (b to evaluate the reliability of our virtual-screening (VS protocol by experimentally testing the "in vitro" activity of selected molecules. Starting from the crystal structure of the DDC-carbidopa complex, a new VS protocol, integrating pharmacophore searches and molecular docking, was developed. Analysis of 15 selected compounds, obtained by filtering the public ZINC database, yielded two molecules that bind to the active site of human DDC and behave as competitive inhibitors with K(i values ≥10 µM. By performing in silico similarity search on the latter compounds followed by a substructure search using the core of the most active compound we identified several competitive inhibitors of human DDC with K(i values in the low micromolar range, unable to bind free PLP, and predicted to not cross the blood-brain barrier. The most potent inhibitor with a K(i value of 500 nM represents a new lead compound, targeting human DDC, that may be the basis for lead optimization in the development of new DDC inhibitors. To our knowledge, a similar approach has not been reported yet in the field of DDC inhibitors discovery.
Shah, Falgun; Mukherjee, Prasenjit; Gut, Jiri; Legac, Jennifer; Rosenthal, Philip J; Tekwani, Babu L; Avery, Mitchell A
2011-04-25
Malaria, in particular that caused by Plasmodium falciparum , is prevalent across the tropics, and its medicinal control is limited by widespread drug resistance. Cysteine proteases of P. falciparum , falcipain-2 (FP-2) and falcipain-3 (FP-3), are major hemoglobinases, validated as potential antimalarial drug targets. Structure-based virtual screening of a focused cysteine protease inhibitor library built with soft rather than hard electrophiles was performed against an X-ray crystal structure of FP-2 using the Glide docking program. An enrichment study was performed to select a suitable scoring function and to retrieve potential candidates against FP-2 from a large chemical database. Biological evaluation of 50 selected compounds identified 21 diverse nonpeptidic inhibitors of FP-2 with a hit rate of 42%. Atomic Fukui indices were used to predict the most electrophilic center and its electrophilicity in the identified hits. Comparison of predicted electrophilicity of electrophiles in identified hits with those in known irreversible inhibitors suggested the soft-nature of electrophiles in the selected target compounds. The present study highlights the importance of focused libraries and enrichment studies in structure-based virtual screening. In addition, few compounds were screened against homologous human cysteine proteases for selectivity analysis. Further evaluation of structure-activity relationships around these nonpeptidic scaffolds could help in the development of selective leads for antimalarial chemotherapy.
Optimization of TRPV6 Calcium Channel Inhibitors Using a 3D Ligand-Based Virtual Screening Method.
Simonin Céline; Awale Mahendra; Brand Michael; van Deursen Ruud; Schwartz Julian; Fine Michael; Kovacs Gergely; Häfliger Pascal; Gyimesi Gergely; Sithampari Abilashan; Charles Roch-Philippe; Hediger Matthias A; Reymond Jean-Louis
2015-01-01
Herein we report the discovery of the first potent and selective inhibitor of TRPV6 a calcium channel overexpressed in breast and prostate cancer and its use to test the effect of blocking TRPV6 mediated Ca(2+) influx on cell growth. The inhibitor was discovered through a computational method xLOS a 3D shape and pharmacophore similarity algorithm a type of ligand based virtual screening (LBVS) method described briefly here. Starting with a single weakly active seed molecule two successive rou...
How to Achieve Better Results Using PASS-Based Virtual Screening: Case Study for Kinase Inhibitors
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Pavel V. Pogodin
2018-04-01
Full Text Available Discovery of new pharmaceutical substances is currently boosted by the possibility of utilization of the Synthetically Accessible Virtual Inventory (SAVI library, which includes about 283 million molecules, each annotated with a proposed synthetic one-step route from commercially available starting materials. The SAVI database is well-suited for ligand-based methods of virtual screening to select molecules for experimental testing. In this study, we compare the performance of three approaches for the analysis of structure-activity relationships that differ in their criteria for selecting of “active” and “inactive” compounds included in the training sets. PASS (Prediction of Activity Spectra for Substances, which is based on a modified Naïve Bayes algorithm, was applied since it had been shown to be robust and to provide good predictions of many biological activities based on just the structural formula of a compound even if the information in the training set is incomplete. We used different subsets of kinase inhibitors for this case study because many data are currently available on this important class of drug-like molecules. Based on the subsets of kinase inhibitors extracted from the ChEMBL 20 database we performed the PASS training, and then applied the model to ChEMBL 23 compounds not yet present in ChEMBL 20 to identify novel kinase inhibitors. As one may expect, the best prediction accuracy was obtained if only the experimentally confirmed active and inactive compounds for distinct kinases in the training procedure were used. However, for some kinases, reasonable results were obtained even if we used merged training sets, in which we designated as inactives the compounds not tested against the particular kinase. Thus, depending on the availability of data for a particular biological activity, one may choose the first or the second approach for creating ligand-based computational tools to achieve the best possible results in
Innovation and Virtual Environments: Towards Virtual Knowledge Brokers
VERONA G; PRANDELLI E.; SAWHNEY M.
2006-01-01
The authors examine the implications of virtual customer environments for supporting the innovation process. By building on the literature of knowledge brokers, they introduce the concept of virtual knowledge brokers — actors who leverage the internet to support third parties’ innovation activities. These actors enable firms to extend their reach in engaging with customers and they also allow firms to have a richer dialogue with customers because of their perceived neutrality. Consequently...
Directory of Open Access Journals (Sweden)
Laura Guasch
Full Text Available BACKGROUND: There has been great interest in determining whether natural products show biological activity toward protein targets of pharmacological relevance. One target of particular interest is DPP-IV whose most important substrates are incretins that, among other beneficial effects, stimulates insulin biosynthesis and secretion. Incretins have very short half-lives because of their rapid degradation by DPP-IV and, therefore, inhibiting this enzyme improves glucose homeostasis. As a result, DPP-IV inhibitors are of considerable interest to the pharmaceutical industry. The main goals of this study were (a to develop a virtual screening process to identify potential DPP-IV inhibitors of natural origin; (b to evaluate the reliability of our virtual-screening protocol by experimentally testing the in vitro activity of selected natural-product hits; and (c to use the most active hit for predicting derivatives with higher binding affinities for the DPP-IV binding site. METHODOLOGY/PRINCIPAL FINDINGS: We predicted that 446 out of the 89,165 molecules present in the natural products subset of the ZINC database would inhibit DPP-IV with good ADMET properties. Notably, when these 446 molecules were merged with 2,342 known DPP-IV inhibitors and the resulting set was classified into 50 clusters according to chemical similarity, there were 12 clusters that contained only natural products for which no DPP-IV inhibitory activity has been previously reported. Nine molecules from 7 of these 12 clusters were then selected for in vitro activity testing and 7 out of the 9 molecules were shown to inhibit DPP-IV (where the remaining two molecules could not be solubilized, preventing the evaluation of their DPP-IV inhibitory activity. Then, the hit with the highest activity was used as a lead compound in the prediction of more potent derivatives. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that our virtual-screening protocol was successful in identifying novel
Virtual screening for novel Staphylococcus Aureus NorA efflux pump inhibitors from natural products.
Thai, Khac-Minh; Ngo, Trieu-Du; Phan, Thien-Vy; Tran, Thanh-Dao; Nguyen, Ngoc-Vinh; Nguyen, Thien-Hai; Le, Minh-Tri
2015-01-01
NorA is a member of the Major Facilitator Superfamily (MFS) drug efflux pumps that have been shown to mediate antibiotic resistance in Staphylococcus aureus (SA). In this study, QSAR analysis, virtual screening and molecular docking were implemented in an effort to discover novel SA NorA efflux pump inhibitors. Originally, a set of 47 structurally diverse compounds compiled from the literature was used to develop linear QSAR models and another set of 15 different compounds were chosen for extra validation. The final model which was estimated by statistical values for the full data set (n = 45, Q(2) = 0.80, RMSE = 0.20) and for the external test set (n = 15, R(2) = 0.60, |res|max = 0.75, |res|min = 0.02) was applied on the collection of 182 flavonoides and the traditional Chinese medicine (TCM) database to screen for novel NorA inhibitors. Finally, 33 lead compounds that met the Lipinski's rules of five/three and had good predicted pIC50 values from in silico screening process were employed to analyze the binding ability by docking studies on NorA homology model in place of its unavailable crystal structures at two active sites, the central channel and the Walker B.
Directory of Open Access Journals (Sweden)
Craig A. Doupnik
2015-01-01
Full Text Available Ion channels represent a large family of membrane proteins with many being well established targets in pharmacotherapy. The ‘druggability’ of heteromeric channels comprised of different subunits remains obscure, due largely to a lack of channel-specific probes necessary to delineate their therapeutic potential in vivo. Our initial studies reported here, investigated the family of inwardly rectifying potassium (Kir channels given the availability of high resolution crystal structures for the eukaryotic constitutively active Kir2.2 channel. We describe a ‘limited’ homology modeling approach that can yield chimeric Kir channels having an outer vestibule structure representing nearly any known vertebrate or invertebrate channel. These computationally-derived channel structures were tested in silico for ‘docking’ to NMR structures of tertiapin (TPN, a 21 amino acid peptide found in bee venom. TPN is a highly selective and potent blocker for the epithelial rat Kir1.1 channel, but does not block human or zebrafish Kir1.1 channel isoforms. Our Kir1.1 channel-TPN docking experiments recapitulated published in vitro findings for TPN-sensitive and TPN-insensitive channels. Additionally, in silico site-directed mutagenesis identified ‘hot spots’ within the channel outer vestibule that mediate energetically favorable docking scores and correlate with sites previously identified with in vitro thermodynamic mutant-cycle analysis. These ‘proof-of-principle’ results establish a framework for virtual screening of re-engineered peptide toxins for interactions with computationally derived Kir channels that currently lack channel-specific blockers. When coupled with electrophysiological validation, this virtual screening approach may accelerate the drug discovery process, and can be readily applied to other ion channels families where high resolution structures are available.
Revisiting Parametric Types and Virtual Classes
DEFF Research Database (Denmark)
Madsen, Anders Bach; Ernst, Erik
2010-01-01
manner, because virtual classes are closely tied to nominal typing. This paper adds new insight about the dichotomy between these two approaches; it illustrates how virtual constraints and type refinements, as recently introduced in gbeta and Scala, enable structural treatment of virtual types; finally...
Virtual Laboratory Enabling Collaborative Research in Applied Vehicle Technologies
Lamar, John E.; Cronin, Catherine K.; Scott, Laura E.
2005-01-01
The virtual laboratory is a new technology, based on the internet, that has had wide usage in a variety of technical fields because of its inherent ability to allow many users to participate simultaneously in instruction (education) or in the collaborative study of a common problem (real-world application). The leadership in the Applied Vehicle Technology panel has encouraged the utilization of this technology in its task groups for some time and its parent organization, the Research and Technology Agency, has done the same for its own administrative use. This paper outlines the application of the virtual laboratory to those fields important to applied vehicle technologies, gives the status of the effort, and identifies the benefit it can have on collaborative research. The latter is done, in part, through a specific example, i.e. the experience of one task group.
Gómez-Bombarelli, Rafael; Aguilera-Iparraguirre, Jorge; Hirzel, Timothy D.; Duvenaud, David; MacLaurin, Dougal; Blood-Forsythe, Martin A.; Chae, Hyun Sik; Einzinger, Markus; Ha, Dong-Gwang; Wu, Tony; Markopoulos, Georgios; Jeon, Soonok; Kang, Hosuk; Miyazaki, Hiroshi; Numata, Masaki; Kim, Sunghan; Huang, Wenliang; Hong, Seong Ik; Baldo, Marc; Adams, Ryan P.; Aspuru-Guzik, Alán
2016-10-01
Virtual screening is becoming a ground-breaking tool for molecular discovery due to the exponential growth of available computer time and constant improvement of simulation and machine learning techniques. We report an integrated organic functional material design process that incorporates theoretical insight, quantum chemistry, cheminformatics, machine learning, industrial expertise, organic synthesis, molecular characterization, device fabrication and optoelectronic testing. After exploring a search space of 1.6 million molecules and screening over 400,000 of them using time-dependent density functional theory, we identified thousands of promising novel organic light-emitting diode molecules across the visible spectrum. Our team collaboratively selected the best candidates from this set. The experimentally determined external quantum efficiencies for these synthesized candidates were as large as 22%.
Chalil Madathil, Kapil; Greenstein, Joel S
2017-11-01
Collaborative virtual reality-based systems have integrated high fidelity voice-based communication, immersive audio and screen-sharing tools into virtual environments. Such three-dimensional collaborative virtual environments can mirror the collaboration among usability test participants and facilitators when they are physically collocated, potentially enabling moderated usability tests to be conducted effectively when the facilitator and participant are located in different places. We developed a virtual collaborative three-dimensional remote moderated usability testing laboratory and employed it in a controlled study to evaluate the effectiveness of moderated usability testing in a collaborative virtual reality-based environment with two other moderated usability testing methods: the traditional lab approach and Cisco WebEx, a web-based conferencing and screen sharing approach. Using a mixed methods experimental design, 36 test participants and 12 test facilitators were asked to complete representative tasks on a simulated online shopping website. The dependent variables included the time taken to complete the tasks; the usability defects identified and their severity; and the subjective ratings on the workload index, presence and satisfaction questionnaires. Remote moderated usability testing methodology using a collaborative virtual reality system performed similarly in terms of the total number of defects identified, the number of high severity defects identified and the time taken to complete the tasks with the other two methodologies. The overall workload experienced by the test participants and facilitators was the least with the traditional lab condition. No significant differences were identified for the workload experienced with the virtual reality and the WebEx conditions. However, test participants experienced greater involvement and a more immersive experience in the virtual environment than in the WebEx condition. The ratings for the virtual
Miller, Kimberly J; Adair, Brooke S; Pearce, Alan J; Said, Catherine M; Ozanne, Elizabeth; Morris, Meg M
2014-03-01
use of virtual reality and commercial gaming systems (VR/gaming) at home by older adults is receiving attention as a means of enabling physical activity. to summarise evidence for the effectiveness and feasibility of VR/gaming system utilisation by older adults at home for enabling physical activity to improve impairments, activity limitations or participation. a systematic review searching 12 electronic databases from 1 January 2000-10 July 2012 using key search terms. Two independent reviewers screened yield articles using pre-determined selection criteria, extracted data using customised forms and applied the Cochrane Collaboration Risk of Bias Tool and the Downs and Black Checklist to rate study quality. fourteen studies investigating the effects of VR/gaming system use by healthy older adults and people with neurological conditions on activity limitations, body functions and physical impairments and cognitive and emotional well-being met the selection criteria. Study quality ratings were low and, therefore, evidence was not strong enough to conclude that interventions were effective. Feasibility was inconsistently reported in studies. Where feasibility was discussed, strong retention (≥70%) and adherence (≥64%) was reported. Initial assistance to use the technologies, and the need for monitoring exertion, aggravation of musculoskeletal symptoms and falls risk were reported. existing evidence to support the feasibility and effectiveness VR/gaming systems use by older adults at home to enable physical activity to address impairments, activity limitations and participation is weak with a high risk of bias. The findings of this review may inform future, more rigorous research.
Virtual Video Prototyping for Healthcare Systems
DEFF Research Database (Denmark)
Bardram, Jakob Eyvind; Bossen, Claus; Lykke-Olesen, Andreas
2002-01-01
Virtual studio technology enables the mixing of physical and digital 3D objects and thus expands the way of representing design ideas in terms of virtual video prototypes, which offers new possibilities for designers by combining elements of prototypes, mock-ups, scenarios, and conventional video....... In this article we report our initial experience in the domain of pervasive healthcare with producing virtual video prototypes and using them in a design workshop. Our experience has been predominantly favourable. The production of a virtual video prototype forces the designers to decide very concrete design...... issues, since one cannot avoid paying attention to the physical, real-world constraints and to details in the usage-interaction between users and technology. From the users' perspective, during our evaluation of the virtual video prototype, we experienced how it enabled users to relate...
Wang, Jing; Wang, Su; Li, Lihong; Fan, Yi; Lu, Hongbing; Liang, Zhengrong
2008-10-01
Computed tomography colonography (CTC) or CT-based virtual colonoscopy (VC) is an emerging tool for detection of colonic polyps. Compared to the conventional fiber-optic colonoscopy, VC has demonstrated the potential to become a mass screening modality in terms of safety, cost, and patient compliance. However, current CTC delivers excessive X-ray radiation to the patient during data acquisition. The radiation is a major concern for screening application of CTC. In this work, we performed a simulation study to demonstrate a possible ultra low-dose CT technique for VC. The ultra low-dose abdominal CT images were simulated by adding noise to the sinograms of the patient CTC images acquired with normal dose scans at 100 mA s levels. The simulated noisy sinogram or projection data were first processed by a Karhunen-Loeve domain penalized weighted least-squares (KL-PWLS) restoration method and then reconstructed by a filtered backprojection algorithm for the ultra low-dose CT images. The patient-specific virtual colon lumen was constructed and navigated by a VC system after electronic colon cleansing of the orally-tagged residue stool and fluid. By the KL-PWLS noise reduction, the colon lumen can successfully be constructed and the colonic polyp can be detected in an ultra low-dose level below 50 mA s. Polyp detection can be found more easily by the KL-PWLS noise reduction compared to the results using the conventional noise filters, such as Hanning filter. These promising results indicate the feasibility of an ultra low-dose CTC pipeline for colon screening with less-stressful bowel preparation by fecal tagging with oral contrast.
Seuss, Hannes; Dankerl, Peter; Cavallaro, Alexander; Uder, Michael; Hammon, Matthias
2016-05-20
To evaluate screening and diagnostic accuracy for the detection of osteoblastic rib lesions using an advanced post-processing package enabling in-plane rib reading in CT-images. We retrospectively assessed the CT-data of 60 consecutive prostate cancer patients by applying dedicated software enabling in-plane rib reading. Reading the conventional multiplanar reconstructions was considered to be the reference standard. To simulate clinical practice, the reader was given 10 s to screen for sclerotic rib lesions in each patient applying both approaches. Afterwards, every rib was evaluated individually with both approaches without a time limit. Sensitivities, specificities, positive/negative predictive values and the time needed for detection were calculated depending on the lesion's size (largest diameter 10 mm). In 53 of 60 patients, all ribs were properly displayed in plane, in five patients ribs were partially displayed correctly, and in two patients none of the ribs were displayed correctly. During the 10-s screening approach all patients with sclerotic rib lesions were correctly identified reading the in-plane images (including the patients without a correct rib segmentation), whereas 14 of 23 patients were correctly identified reading conventional multiplanar images. Overall screening sensitivity, specificity, and positive/negative predictive values were 100/27.0/46.0/100 %, respectively, for in-plane reading and 60.9/100/100/80.4 %, respectively, for multiplanar reading. Overall diagnostic (no time limit) sensitivity, specificity, and positive/negative predictive values of in-plane reading were 97.8/92.8/74.6/99.5 %, respectively. False positive results predominantly occurred for lesions <5 mm in size. In-plane reading of the ribs allows reliable detection of osteoblastic lesions for screening purposes. The limited specificity results from false positives predominantly occurring for small lesions.
Virtual Reality Design: How Head-Mounted Displays Change Design Paradigms of Virtual Reality Worlds
Directory of Open Access Journals (Sweden)
Christian Stein
2016-09-01
Full Text Available With the upcoming generation of virtual reality HMDs, new virtual worlds, scenarios, and games are created especially for them. These are no longer bound to a remote screen or a relatively static user, but to an HMD as a more immersive device. This article discusses requirements for virtual scenarios implemented in new-generation HMDs to achieve a comfortable user experience. Furthermore, the effects of positional tracking are introduced and the relation between the user’s virtual and physical body is analyzed. The observations made are exemplified by existing software prototypes. They indicate how the term “virtual reality,” with all its loaded connotations, may be reconceptualized to express the peculiarities of HMDs in the context of gaming, entertainment, and virtual experiences.
Natural Walking in Virtual Reality: A Review
DEFF Research Database (Denmark)
Nilsson, Niels Chr.; Serafin, Stefania; Steinicke, Franke
2018-01-01
Recent technological developments have finally brought virtual reality (VR) out of the laboratory and into the hands of developers and consumers. However, a number of challenges remain. Virtual travel is one of the most common and universal tasks performed inside virtual environments, yet enabling...... users to navigate virtual environments is not a trivial challenge—especially if the user is walking. In this article, we initially provide an overview of the numerous virtual travel techniques that have been proposed prior to the commercialization of VR. Then we turn to the mode of travel...... that is the most difficult to facilitate, that is, walking. The challenge of providing users with natural walking experiences in VR can be divided into two separate, albeit related, challenges: (1) enabling unconstrained walking in virtual worlds that are larger than the tracked physical space and (2) providing...
Sugumar, Ramya; Adithavarman, Abhinand Ponneri; Dakshinamoorthi, Anusha; David, Darling Chellathai; Ragunath, Padmavathi Kannan
2016-03-01
Pneumocystis jirovecii is a fungus that causes Pneumocystis pneumonia in HIV and other immunosuppressed patients. Treatment of Pneumocystis pneumonia with the currently available antifungals is challenging and associated with considerable adverse effects. There is a need to develop drugs against novel targets with minimal human toxicities. Histone Acetyl Transferase (HAT) Rtt109 is a potential therapeutic target in Pneumocystis jirovecii species. HAT is linked to transcription and is required to acetylate conserved lysine residues on histone proteins by transferring an acetyl group from acetyl CoA to form e-N-acetyl lysine. Therefore, inhibitors of HAT can be useful therapeutic options in Pneumocystis pneumonia. To screen phytochemicals against (HAT) Rtt109 using bioinformatics tool. The tertiary structure of Pneumocystis jirovecii (HAT) Rtt109 was modeled by Homology Modeling. The ideal template for modeling was obtained by performing Psi BLAST of the protein sequence. Rtt109-AcCoA/Vps75 protein from Saccharomyces cerevisiae (PDB structure 3Q35) was chosen as the template. The target protein was modeled using Swiss Modeler and validated using Ramachandran plot and Errat 2. Comprehensive text mining was performed to identify phytochemical compounds with antipneumonia and fungicidal properties and these compounds were filtered based on Lipinski's Rule of 5. The chosen compounds were subjected to virtual screening against the target protein (HAT) Rtt109 using Molegro Virtual Docker 4.5. Osiris Property Explorer and Open Tox Server were used to predict ADME-T properties of the chosen phytochemicals. Tertiary structure model of HAT Rtt 109 had a ProSA score of -6.57 and Errat 2 score of 87.34. Structure validation analysis by Ramachandran plot for the model revealed 97% of amino acids were in the favoured region. Of all the phytochemicals subjected to virtual screening against the target protein (HAT) Rtt109, baicalin exhibited highest binding affinity towards the
Directory of Open Access Journals (Sweden)
Liansheng Qiao
2016-12-01
Full Text Available Adlay (Coix larchryma-jobi L. was the commonly used Traditional Chinese Medicine (TCM with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM, was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM proteins based on
Gennaro, Silvano De
The VENUS (Virtual Environment Navigation in the Underground Sites) project is probably the largest Virtual Reality application to Engineering design in the world. VENUS is just over one year old and offers a fully immersive and stereoscopic "flythru" of the LHC pits for the proposed experiments, including the experimental area equipment and the surface models that are being prepared for a territorial impact study. VENUS' Virtual Prototypes are an ideal replacement for the wooden models traditionally build for the past CERN machines, as they are generated directly from the EUCLID CAD files, therefore they are totally reliable, they can be updated in a matter of minutes, and they allow designers to explore them from inside, in a one-to-one scale. Navigation can be performed on the computer screen, on a stereoscopic large projection screen, or in immersive conditions, with an helmet and 3D mouse. By using specialised collision detection software, the computer can find optimal paths to lower each detector part into the pits and position it to destination, letting us visualize the whole assembly probess. During construction, these paths can be fed to a robot controller, which can operate the bridge cranes and build LHC almost without human intervention. VENUS is currently developing a multiplatform VR browser that will let the whole HEP community access LHC's Virtual Protoypes over the web. Many interesting things took place during the conference on Virtual Reality. For more information please refer to the Virtual Reality section.
Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar
2016-12-13
Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design.
Directory of Open Access Journals (Sweden)
Irene Maffucci
2018-03-01
Full Text Available Nwat-MMGBSA is a variant of MM-PB/GBSA based on the inclusion of a number of explicit water molecules that are the closest to the ligand in each frame of a molecular dynamics trajectory. This method demonstrated improved correlations between calculated and experimental binding energies in both protein-protein interactions and ligand-receptor complexes, in comparison to the standard MM-GBSA. A protocol optimization, aimed to maximize efficacy and efficiency, is discussed here considering penicillopepsin, HIV1-protease, and BCL-XL as test cases. Calculations were performed in triplicates on both classic HPC environments and on standard workstations equipped by a GPU card, evidencing no statistical differences in the results. No relevant differences in correlation to experiments were also observed when performing Nwat-MMGBSA calculations on 4 or 1 ns long trajectories. A fully automatic workflow for structure-based virtual screening, performing from library set-up to docking and Nwat-MMGBSA rescoring, has then been developed. The protocol has been tested against no rescoring or standard MM-GBSA rescoring within a retrospective virtual screening of inhibitors of AmpC β-lactamase and of the Rac1-Tiam1 protein-protein interaction. In both cases, Nwat-MMGBSA rescoring provided a statistically significant increase in the ROC AUCs of between 20 and 30%, compared to docking scoring or to standard MM-GBSA rescoring.
Maffucci, Irene; Hu, Xiao; Fumagalli, Valentina; Contini, Alessandro
2018-03-01
Nwat-MMGBSA is a variant of MM-PB/GBSA based on the inclusion of a number of explicit water molecules that are the closest to the ligand in each frame of a molecular dynamics trajectory. This method demonstrated improved correlations between calculated and experimental binding energies in both protein-protein interactions and ligand-receptor complexes, in comparison to the standard MM-GBSA. A protocol optimization, aimed to maximize efficacy and efficiency, is discussed here considering penicillopepsin, HIV1-protease, and BCL-XL as test cases. Calculations were performed in triplicates on both classic HPC environments and on standard workstations equipped by a GPU card, evidencing no statistical differences in the results. No relevant differences in correlation to experiments were also observed when performing Nwat-MMGBSA calculations on 4 ns or 1 ns long trajectories. A fully automatic workflow for structure-based virtual screening, performing from library set-up to docking and Nwat-MMGBSA rescoring, has then been developed. The protocol has been tested against no rescoring or standard MM-GBSA rescoring within a retrospective virtual screening of inhibitors of AmpC β-lactamase and of the Rac1-Tiam1 protein-protein interaction. In both cases, Nwat-MMGBSA rescoring provided a statistically significant increase in the ROC AUCs of between 20% and 30%, compared to docking scoring or to standard MM-GBSA rescoring.
BET Bromodomain Inhibitors with One-Step Synthesis Discovered from Virtual Screen.
Ayoub, Alex M; Hawk, Laura M L; Herzig, Ryan J; Jiang, Jiewei; Wisniewski, Andrea J; Gee, Clifford T; Zhao, Peiliang; Zhu, Jin-Yi; Berndt, Norbert; Offei-Addo, Nana K; Scott, Thomas G; Qi, Jun; Bradner, James E; Ward, Timothy R; Schönbrunn, Ernst; Georg, Gunda I; Pomerantz, William C K
2017-06-22
Chemical inhibition of epigenetic regulatory proteins BrdT and Brd4 is emerging as a promising therapeutic strategy in contraception, cancer, and heart disease. We report an easily synthesized dihydropyridopyrimidine pan-BET inhibitor scaffold, which was uncovered via a virtual screen followed by testing in a fluorescence anisotropy assay. Dihydropyridopyimidine 3 was subjected to further characterization and is highly selective for the BET family of bromodomains. Structure-activity relationship data and ligand deconstruction highlight the importance of the substitution of the uracil moiety for potency and selectivity. Compound 3 was also cocrystallized with Brd4 for determining the ligand binding pose and rationalizing subsequent structure-activity data. An additional series of dihydropyridopyrimidines was synthesized to exploit the proximity of a channel near the ZA loop of Brd4, leading to compounds with submicromolar affinity and cellular target engagement. Given these findings, novel and easily synthesized inhibitors are being introduced to the growing field of bromodomain inhibitor development.
BET Bromodomain Inhibitors with One-Step Synthesis Discovered from Virtual Screen
Energy Technology Data Exchange (ETDEWEB)
Ayoub, Alex M.; Hawk, Laura M.L.; Herzig, Ryan J.; Jiang, Jiewei; Wisniewski, Andrea J.; Gee, Clifford T.; Zhao, Peiliang; Zhu, Jin-Yi; Berndt, Norbert; Offei-Addo, Nana K.; Scott, Thomas G.; Qi, Jun; Bradner, James E.; Ward, Timothy R.; Schönbrunn, Ernst; Georg, Gunda I.; Pomerantz, William C.K. (Moffitt); (UMM); (Harvard-Med)
2017-06-06
Chemical inhibition of epigenetic regulatory proteins BrdT and Brd4 is emerging as a promising therapeutic strategy in contraception, cancer, and heart disease. We report an easily synthesized dihydropyridopyrimidine pan-BET inhibitor scaffold, which was uncovered via a virtual screen followed by testing in a fluorescence anisotropy assay. Dihydropyridopyimidine 3 was subjected to further characterization and is highly selective for the BET family of bromodomains. Structure–activity relationship data and ligand deconstruction highlight the importance of the substitution of the uracil moiety for potency and selectivity. Compound 3 was also cocrystallized with Brd4 for determining the ligand binding pose and rationalizing subsequent structure–activity data. An additional series of dihydropyridopyrimidines was synthesized to exploit the proximity of a channel near the ZA loop of Brd4, leading to compounds with submicromolar affinity and cellular target engagement. Given these findings, novel and easily synthesized inhibitors are being introduced to the growing field of bromodomain inhibitor development.
Virtual Screening and Prediction of Site of Metabolism for Cytochrome P450 1A2 Ligands
DEFF Research Database (Denmark)
Vasanthanathan, P.; Hritz, Jozef; Taboureau, Olivier
2009-01-01
questions have been addressed: 1. Binding orientations and conformations were successfully predicted for various substrates. 2. A virtual screen was performed with satisfying enrichment rates. 3. A classification of individual compounds into active and inactive was performed. It was found that while docking...... can be used successfully to address the first two questions, it seems to be more difficult to perform the classification. Different scoring functions were included, and the well-characterized water molecule in the active site was included in various ways. Results are compared to experimental data...
Speck-Planche, Alejandro; Cordeiro, M N D S
2014-02-10
Escherichia coli remains one of the principal pathogens that cause nosocomial infections, medical conditions that are increasingly common in healthcare facilities. E. coli is intrinsically resistant to many antibiotics, and multidrug-resistant strains have emerged recently. Chemoinformatics has been a great ally of experimental methodologies such as high-throughput screening, playing an important role in the discovery of effective antibacterial agents. However, there is no approach that can design safer anti-E. coli agents, because of the multifactorial nature and complexity of bacterial diseases and the lack of desirable ADMET (absorption, distribution, metabolism, elimination, and toxicity) profiles as a major cause of disapproval of drugs. In this work, we introduce the first multitasking model based on quantitative-structure biological effect relationships (mtk-QSBER) for simultaneous virtual prediction of anti-E. coli activities and ADMET properties of drugs and/or chemicals under many experimental conditions. The mtk-QSBER model was developed from a large and heterogeneous data set of more than 37800 cases, exhibiting overall accuracies of >95% in both training and prediction (validation) sets. The utility of our mtk-QSBER model was demonstrated by performing virtual prediction of properties for the investigational drug avarofloxacin (AVX) under 260 different experimental conditions. Results converged with the experimental evidence, confirming the remarkable anti-E. coli activities and safety of AVX. Predictions also showed that our mtk-QSBER model can be a promising computational tool for virtual screening of desirable anti-E. coli agents, and this chemoinformatic approach could be extended to the search for safer drugs with defined pharmacological activities.
Virtual screening using the ligand ZINC database for novel lipoxygenase-3 inhibitors.
Monika; Kour, Janmeet; Singh, Kulwinder
2013-01-01
The leukotrienes constitute a group of arachidonic acid-derived compounds with biologic activities suggesting important roles in inflammation and immediate hypersensitivity. Epidermis-type lipoxygenase-3 (ALOXE3), a distinct subclass within the multigene family of mammalian lipoxygenases, is a novel isoenzyme involved in the metabolism of leukotrienes and plays a very important role in skin barrier functions. Lipoxygenase selective inhibitors such as azelastine and zileuton are currently used to reduce inflammatory response. Nausea, pharyngolaryngeal pain, headache, nasal burning and somnolence are the most frequently reported adverse effects of these drugs. Therefore, there is still a need to develop more potent lipoxygenase inhibitors. In this paper, we report the screening of various compounds from the ZINC database (contains over 21 million compounds) using the Molegro Virtual Docker software against the ALOXE3 protein. Screening was performed using molecular constraints tool to filter compounds with physico-chemical properties similar to the 1N8Q bound ligand protocatechuic acid. The analysis resulted in 4319 Lipinski compliant hits which are docked and scored to identify structurally novel ligands that make similar interactions to those of known ligands or may have different interactions with other parts of the binding site. Our screening approach identified four molecules ZINC84299674; ZINC76643455; ZINC84299122 & ZINC75626957 with MolDock score of -128.901, -120.22, -116.873 & - 102.116 kcal/mol, respectively. Their energy scores were better than the 1N8Q bound co-crystallized ligand protocatechuic acid (with MolDock score of -77.225 kcal/mol). All the ligands were docked within the binding pocket forming interactions with amino acid residues.
Podshivalov, D.; Mandzhieva, Yu. B.; Sidorov-Biryukov, D. D.; Timofeev, V. I.; Kuranova, I. P.
2018-01-01
Bacterial imidazoleglycerol-phosphate dehydratase from Mycobacterium tuberculosis (HisB- Mt) is a convenient target for the discovery of selective inhibitors as potential antituberculosis drugs. The virtual screening was performed to find compounds suitable for the design of selective inhibitors of HisB- Mt. The positions of four ligands, which were selected based on the docking scoring function and docked to the activesite region of the enzyme, were refined by molecular dynamics simulation. The nearest environment of the ligands was determined. These compounds selectively bind to functionally essential active-site residues, thus blocking access of substrates to the active site of the enzyme, and can be used as lead compounds for the design of selective inhibitors of HisB- M.
Sakkiah, Sugunadevi; Thangapandian, Sundarapandian; John, Shalini; Lee, Keun Woo
2011-01-01
This study was performed to find the selective chemical features for Aurora kinase-B inhibitors using the potent methods like Hip-Hop, virtual screening, homology modeling, molecular dynamics and docking. The best hypothesis, Hypo1 was validated toward a wide range of test set containing the selective inhibitors of Aurora kinase-B. Homology modeling and molecular dynamics studies were carried out to perform the molecular docking studies. The best hypothesis Hypo1 was used as a 3D query to screen the chemical databases. The screened molecules from the databases were sorted based on ADME and drug like properties. The selective hit compounds were docked and the hydrogen bond interactions with the critical amino acids present in Aurora kinase-B were compared with the chemical features present in the Hypo1. Finally, we suggest that the chemical features present in the Hypo1 are vital for a molecule to inhibit the Aurora kinase-B activity.
Alawa, Karam A.; Sayed, Mohamed; Arboleda, Alejandro; Durkee, Heather A.; Aguilar, Mariela C.; Lee, Richard K.
2017-02-01
Glaucoma is the leading cause of irreversible blindness worldwide. Due to its wide prevalence, effective screening tools are necessary. The purpose of this project is to design and evaluate a system that enables portable, cost effective, smartphone based visual field screening based on frequency doubling technology. The system is comprised of an Android smartphone to display frequency doubling stimuli and handle processing, a Bluetooth remote for user input, and a virtual reality headset to simulate the exam. The LG Nexus 5 smartphone and BoboVR Z3 virtual reality headset were used for their screen size and lens configuration, respectively. The system is capable of running the C-20, N-30, 24-2, and 30-2 testing patterns. Unlike the existing system, the smartphone FDT tests both eyes concurrently by showing the same background to both eyes but only displaying the stimulus to one eye at a time. Both the Humphrey Zeiss FDT and the smartphone FDT were tested on five subjects without a history of ocular disease with the C-20 testing pattern. The smartphone FDT successfully produced frequency doubling stimuli at the correct spatial and temporal frequency. Subjects could not tell which eye was being tested. All five subjects preferred the smartphone FDT to the Humphrey Zeiss FDT due to comfort and ease of use. The smartphone FDT is a low-cost, portable visual field screening device that can be used as a screening tool for glaucoma.
Donovan, Diane; Loch, Birgit
2013-01-01
How can active learning, peer learning and prompt feedback be achieved in large first-year mathematics classes? Further, what technologies may support these aims? In this article, we assert that test revision sessions in first-year mathematics held in a technology-enhanced lecture theatre can be highly interactive with students solving problems, learning from each other and receiving immediate feedback. This is facilitated by pen-enabled screens and synchronization software. We argue that the educational benefits achievable through the technology do outweigh the technological distractions, and that these benefits can be achieved by focused, targeted one-off sessions and not only by a semester-long, regular approach. Repeat mid-semester test revision sessions were offered on a non-compulsory basis using pen-enabled screens for all students. Students worked practice test questions and marked solutions to mathematical problems on the screens. Students' work was then displayed anonymously for their peers to see. Answers were discussed with the whole class. We discuss outcomes from two offerings of these sessions using student feedback and lecturer reflections and show the impact of participation on self-reported student confidence. Pedagogical approaches that the technology allowed for the first time in a large class are highlighted. Students responded uniformly positively.
Directory of Open Access Journals (Sweden)
Yeonjin Jeong
2017-01-01
Full Text Available We consider a multidevice network with asymmetric antenna configurations which supports not only communications between an access point and devices but also device-to-device (D2D communications for the Internet of things. For the network, we propose the transmit and receive beamforming with the channel state information (CSI for virtual multiple-input multiple-output (MIMO enabled by D2D receive cooperation. We analyze the sum rate achieved by a device pair in the proposed method and identify the strategies to improve the sum rate of the device pair. We next present a distributed algorithm and its equivalent algorithm for device pairing to maximize the throughput of the multidevice network. Simulation results confirm the advantages of the transmit CSI and D2D cooperation as well as the validity of the distributive algorithm.
A Virtual Environments Editor for Driving Scenes
Directory of Open Access Journals (Sweden)
Ronald R. Mourant
2003-12-01
Full Text Available The goal of this project was to enable the rapid creation of three-dimensional virtual driving environments. We designed and implemented a high-level scene editor that allows a user to construct a driving environment by pasting icons that represent 1 road segments, 2 road signs, 3 trees and 4 buildings. These icons represent two- and three-dimensional objects that have been predesigned. Icons can be placed in the scene at specific locations (x, y, and z coordinates. The editor includes the capability of a user to "drive" a vehicle using a computer mouse for steering, accelerating and braking. At any time during the process of building a virtual environment, a user may switch to "Run Mode" and inspect the three-dimensional scene by "driving" through it using the mouse. Adjustments and additions can be made to the virtual environment by going back to "Build Mode". Once a user is satisfied with the threedimensional virtual environment, it can be saved in a file. The file can used with Java3D software that enables the traversing of three-dimensional environments. The process of building virtual environments from predesigned icons can be applied to many other application areas. It will enable novice computer users to rapidly construct and use three-dimensional virtual environments.
Kireeva, Natalia; Pervov, Vladislav S
2017-08-09
The organic electrolytes of most current commercial rechargeable Li-ion batteries (LiBs) are flammable, toxic, and have limited electrochemical energy windows. All-solid-state battery technology promises improved safety, cycling performance, electrochemical stability, and possibility of device miniaturization and enables a number of breakthrough technologies towards the development of new high power and energy density microbatteries for electronics with low processing cost, solid oxide fuel cells, electrochromic devices, etc. Currently, rational materials design is attracting significant attention, which has resulted in a strong demand for methodologies that can accelerate the design of materials with tailored properties; cheminformatics can be considered as an efficient tool in this respect. This study was focused on several aspects: (i) identification of the parameters responsible for high Li-ion conductivity in garnet structured oxides; (ii) development of quantitative models to elucidate composition-structure-Li ionic conductivity relationships, taking into account the experimental details of sample preparation; (iii) circumscription of the materials space of solid garnet-type electrolytes, which is attractive for virtual screening. Several candidate compounds have been recommended for synthesis as potential solid state electrolyte materials.
2012-01-01
The changing manufacturing environment requires more responsive and adaptable manufacturing systems. The theme of the 4th International Conference on Changeable, Agile, Reconfigurable and Virtual production (CARV2011) is “Enabling Manufacturing Competitiveness and Economic Sustainability”. Leading edge research and best implementation practices and experiences, which address these important issues and challenges, are presented. The proceedings include advances in manufacturing systems design, planning, evaluation, control and evolving paradigms such as mass customization, personalization, changeability, re-configurability and flexibility. New and important concepts such as the dynamic product families and platforms, co-evolution of products and systems, and methods for enhancing manufacturing systems’ economic sustainability and prolonging their life to produce more than one product generation are treated. Enablers of change in manufacturing systems, production volume and capability scalability and man...
Sirci, F.; Istyastono, E.P.; Vischer, H.F.; Nijmeijer, S.; Kuijer, M.; Kooistra, A.J.; Wijtmans, M.; Mannhold, R.; Leurs, R.; de Esch, I.J.P.; de Graaf, C.
2012-01-01
Virtual fragment screening (VFS) is a promising new method that uses computer models to identify small, fragment-like biologically active molecules as useful starting points for fragment-based drug discovery (FBDD). Training sets of true active and inactive fragment-like molecules to construct and
Directory of Open Access Journals (Sweden)
Sereina Riniker
2017-07-01
Full Text Available The first challenge in the 2014 competition launched by the Teach-Discover-Treat (TDT initiative asked for the development of a tutorial for ligand-based virtual screening, based on data from a primary phenotypic high-throughput screen (HTS against malaria. The resulting Workflows were applied to select compounds from a commercial database, and a subset of those were purchased and tested experimentally for anti-malaria activity. Here, we present the two most successful Workflows, both using machine-learning approaches, and report the results for the 114 compounds tested in the follow-up screen. Excluding the two known anti-malarials quinidine and amodiaquine and 31 compounds already present in the primary HTS, a high hit rate of 57% was found.
Virtual Reality Interaction Using Mobile Devices
Aseeri, Sahar A.
2013-07-01
With the use of an immersive display system such as CAVE system, the user is able to realize a 3D immersive virtual environment realistically. However, interacting with virtual worlds in CAVE systems using traditional input devices to perform easy operations such as manipulation, object selection, and navigation is often difficult. This difficulty could diminish the immersion and sense of presence when it comes to 3D virtual environment tasks. Our research aims to implement and evaluate alternative approaches of interaction with immersive virtual environments on mobile devices for manipulation and object selection tasks. As many researchers have noted, using a mobile device as an interaction device has a number of advantages, including built-in display, built-in control, and touch screen facility. These advantages facilitate simple tasks within immersive virtual environments. This research proposes new methods using mobile devices like Smart-phones to perform di↵erent kinds of interactions both as an input device, (e.g. performing selection and manipulation of objects) and as an output device (e.g. utilizing the screen as an extra view for a virtual camera or information display). Moreover, we developed a prototype system to demonstrate and informally evaluate these methods. The research conclusion suggests using mobile devices as a 3D-controller. This will be a more intuitive approach to interact within the virtual environment.
Virtual Video Prototyping of Pervasive Healthcare Systems
DEFF Research Database (Denmark)
Bardram, Jakob Eyvind; Bossen, Claus; Madsen, Kim Halskov
2002-01-01
Virtual studio technology enables the mixing of physical and digital 3D objects and thus expands the way of representing design ideas in terms of virtual video prototypes, which offers new possibilities for designers by combining elements of prototypes, mock-ups, scenarios, and conventional video....... In this article we report our initial experience in the domain of pervasive healthcare with producing virtual video prototypes and using them in a design workshop. Our experience has been predominantly favourable. The production of a virtual video prototype forces the designers to decide very concrete design...... issues, since one cannot avoid paying attention to the physical, real-world constraints and to details in the usage-interaction between users and technology. From the users' perspective, during our evaluation of the virtual video prototype, we experienced how it enabled users to relate...
Sulfonylureas and Glinides as New PPARγ Agonists:. Virtual Screening and Biological Assays
Scarsi, Marco; Podvinec, Michael; Roth, Adrian; Hug, Hubert; Kersten, Sander; Albrecht, Hugo; Schwede, Torsten; Meyer, Urs A.; Rücker, Christoph
2007-12-01
This work combines the predictive power of computational drug discovery with experimental validation by means of biological assays. In this way, a new mode of action for type 2 diabetes drugs has been unvealed. Most drugs currently employed in the treatment of type 2 diabetes either target the sulfonylurea receptor stimulating insulin release (sulfonylureas, glinides), or target PPARγ improving insulin resistance (thiazolidinediones). Our work shows that sulfonylureas and glinides bind to PPARγ and exhibit PPARγ agonistic activity. This result was predicted in silico by virtual screening and confirmed in vitro by three biological assays. This dual mode of action of sulfonylureas and glinides may open new perspectives for the molecular pharmacology of antidiabetic drugs, since it provides evidence that drugs can be designed which target both the sulfonylurea receptor and PPARγ. Targeting both receptors could in principle allow to increase pancreatic insulin secretion, as well as to improve insulin resistance.
Displays enabling mobile multimedia
Kimmel, Jyrki
2007-02-01
With the rapid advances in telecommunications networks, mobile multimedia delivery to handsets is now a reality. While a truly immersive multimedia experience is still far ahead in the mobile world, significant advances have been made in the constituent audio-visual technologies to make this become possible. One of the critical components in multimedia delivery is the mobile handset display. While such alternatives as headset-style near-to-eye displays, autostereoscopic displays, mini-projectors, and roll-out flexible displays can deliver either a larger virtual screen size than the pocketable dimensions of the mobile device can offer, or an added degree of immersion by adding the illusion of the third dimension in the viewing experience, there are still challenges in the full deployment of such displays in real-life mobile communication terminals. Meanwhile, direct-view display technologies have developed steadily, and can provide a development platform for an even better viewing experience for multimedia in the near future. The paper presents an overview of the mobile display technology space with an emphasis on the advances and potential in developing direct-view displays further to meet the goal of enabling multimedia in the mobile domain.
Development of a virtual speaking simulator using Image Based Rendering.
Lee, J M; Kim, H; Oh, M J; Ku, J H; Jang, D P; Kim, I Y; Kim, S I
2002-01-01
The fear of speaking is often cited as the world's most common social phobia. The rapid growth of computer technology has enabled the use of virtual reality (VR) for the treatment of the fear of public speaking. There are two techniques for building virtual environments for the treatment of this fear: a model-based and a movie-based method. Both methods have the weakness that they are unrealistic and not controllable individually. To understand these disadvantages, this paper presents a virtual environment produced with Image Based Rendering (IBR) and a chroma-key simultaneously. IBR enables the creation of realistic virtual environments where the images are stitched panoramically with the photos taken from a digital camera. And the use of chroma-keys puts virtual audience members under individual control in the environment. In addition, real time capture technique is used in constructing the virtual environments enabling spoken interaction between the subject and a therapist or another subject.
Albright, Glenn; Bryan, Craig; Adam, Cyrille; McMillan, Jeremiah; Shockley, Kristen
2017-07-01
Primary health care professionals are in an excellent position to identify, screen, and conduct brief interventions for patients with mental health and substance use disorders. However, discomfort in initiating conversations about behavioral health, time concerns, lack of knowledge about screening tools, and treatment resources are barriers. This study examines the impact of an online simulation where users practice role-playing with emotionally responsive virtual patients to learn motivational interviewing strategies to better manage screening, brief interventions, and referral conversations. Baseline data were collected from 227 participants who were then randomly assigned into the treatment or wait-list control groups. Treatment group participants then completed the simulation, postsimulation survey, and 3-month follow-up survey. Results showed significant increases in knowledge/skill to identify and engage in collaborative decision making with patients. Results strongly suggest that role-play simulation experiences can be an effective means of teaching screening and brief intervention.
Manoharan, Prabu; Chennoju, Kiranmai; Ghoshal, Nanda
2015-07-01
BACE1 is an attractive target in Alzheimer's disease (AD) treatment. A rational drug design effort for the inhibition of BACE1 is actively pursued by researchers in both academic and pharmaceutical industries. This continued effort led to the steady accumulation of BACE1 crystal structures, co-complexed with different classes of inhibitors. This wealth of information is used in this study to develop target specific proteochemometric models and these models are exploited for predicting the prospective BACE1 inhibitors. The models developed in this study have performed excellently in predicting the computationally generated poses, separately obtained from single and ensemble docking approaches. The simple protein-ligand contact (SPLC) model outperforms other sophisticated high end models, in virtual screening performance, developed during this study. In an attempt to account for BACE1 protein active site flexibility information in predictive models, we included the change in the area of solvent accessible surface and the change in the volume of solvent accessible surface in our models. The ensemble and single receptor docking results obtained from this study indicate that the structural water mediated interactions improve the virtual screening results. Also, these waters are essential for recapitulating bioactive conformation during docking study. The proteochemometric models developed in this study can be used for the prediction of BACE1 inhibitors, during the early stage of AD drug discovery.
Analysis of a Moon outpost for Mars enabling technologies through a Virtual Reality environment
Casini, Andrea E. M.; Maggiore, Paolo; Viola, Nicole; Basso, Valter; Ferrino, Marinella; Hoffman, Jeffrey A.; Cowley, Aidan
2018-02-01
The Moon is now being considered as the starting point for human exploration of the Solar System beyond low-Earth orbit. Many national space agencies are actively advocating to build up a lunar surface habitat capability starting from 2030 or earlier: according to ESA Technology Roadmaps for Exploration this should be the result of a broad international cooperation. Taking into account an incremental approach to reduce risks and costs of space missions, a lunar outpost can be considered as a test bed towards Mars, allowing to validate enabling technologies, such as water processing, waste management, power generation and storage, automation, robotics and human factors. Our natural satellite is rich in resources that could be used to pursue such a goal through a necessary assessment of ISRU techniques. The aim of this research is the analysis of a Moon outpost dedicated to the validation of enabling technologies for human space exploration. The main building blocks of the outpost are identified and feasible evolutionary scenarios are depicted, to highlight the incremental steps to build up the outpost. Main aspects that are dealt with include outpost location and architecture, as well as ISRU facilities, which in a far term future can help reduce the mass at launch, by producing hydrogen and oxygen for consumables, ECLSS, and propellant for Earth-Moon sorties and Mars journeys. A test outpost is implemented in a Virtual Reality (VR) environment as a first proof-of-concepts, where the elements are computer-based mock-ups. The VR facility has a first-person interactive perspective, allowing for specific in-depth analyses of ergonomics and operations. The feedbacks of these analyses are crucial to highlight requirements that might otherwise be overlooked, while their general outputs are fundamental to write down procedures. Moreover, the mimic of astronauts' EVAs is useful for pre-flight training, but can also represent an additional tool for failures troubleshooting
Composable processor virtualization for embedded systems
Molnos, A.M.; Milutinovic, A.; She, D.; Goossens, K.G.W.
2010-01-01
Processor virtualization divides a physical processor's time among a set of virual machines, enabling efficient hardware utilization, application security and allowing co-existence of different operating systems on the same processor. Through initially intended for the server domain, virtualization
On Being Bored and Lost (in Virtuality)
Moore, Kristen; Pflugfelder, Ehren Helmut
2010-01-01
Education in virtual worlds has the potential, it seems, for engaging students in innovative ways and for enabling new discourses on a host of issues. Virtual locations like "Second Life," "Kaneva," or "World of Warcraft," among other multi-user virtual environments (MUVEs), also come with unique challenges for educators as they consider the…
Directory of Open Access Journals (Sweden)
Shachar Maidenbaum
Full Text Available Virtual worlds and environments are becoming an increasingly central part of our lives, yet they are still far from accessible to the blind. This is especially unfortunate as such environments hold great potential for them for uses such as social interaction, online education and especially for use with familiarizing the visually impaired user with a real environment virtually from the comfort and safety of his own home before visiting it in the real world. We have implemented a simple algorithm to improve this situation using single-point depth information, enabling the blind to use a virtual cane, modeled on the "EyeCane" electronic travel aid, within any virtual environment with minimal pre-processing. Use of the Virtual-EyeCane, enables this experience to potentially be later used in real world environments with identical stimuli to those from the virtual environment. We show the fast-learned practical use of this algorithm for navigation in simple environments.
Terzopoulos, Demetri; Qureshi, Faisal Z.
Computer vision and sensor networks researchers are increasingly motivated to investigate complex multi-camera sensing and control issues that arise in the automatic visual surveillance of extensive, highly populated public spaces such as airports and train stations. However, they often encounter serious impediments to deploying and experimenting with large-scale physical camera networks in such real-world environments. We propose an alternative approach called "Virtual Vision", which facilitates this type of research through the virtual reality simulation of populated urban spaces, camera sensor networks, and computer vision on commodity computers. We demonstrate the usefulness of our approach by developing two highly automated surveillance systems comprising passive and active pan/tilt/zoom cameras that are deployed in a virtual train station environment populated by autonomous, lifelike virtual pedestrians. The easily reconfigurable virtual cameras distributed in this environment generate synthetic video feeds that emulate those acquired by real surveillance cameras monitoring public spaces. The novel multi-camera control strategies that we describe enable the cameras to collaborate in persistently observing pedestrians of interest and in acquiring close-up videos of pedestrians in designated areas.
Directory of Open Access Journals (Sweden)
Pathan AAK
2016-05-01
Full Text Available Akbar Ali Khan Pathan,1,2,* Bhavana Panthi,3,* Zahid Khan,1 Purushotham Reddy Koppula,4–6 Mohammed Saud Alanazi,1 Sachchidanand,3 Narasimha Reddy Parine,1 Mukesh Chourasia3,* 1Genome Research Chair (GRC, Department of Biochemistry, College of Science, King Saud University, 2Integrated Gulf Biosystems, Riyadh, Kingdom of Saudi Arabia; 3Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Hajipur, India; 4Department of Internal Medicine, School of Medicine, 5Harry S. Truman Memorial Veterans Affairs Hospital, 6Department of Radiology, School of Medicine, Columbia, MO, USA *These authors contributed equally to this work Objective: Kirsten rat sarcoma (K-Ras protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods: In the present study, we targeted the nucleotide-binding site in the “on” and “off” state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results: Interestingly, the designed compounds exhibit a binding preference for the
Virtual radiology rounds: adding value in the digital era
International Nuclear Information System (INIS)
Fefferman, Nancy R.; Strubel, Naomi A.; Prithiani, Chandan; Chakravarti, Sujata; Caprio, Martha; Recht, Michael P.
2016-01-01
To preserve radiology rounds in the changing health care environment, we have introduced virtual radiology rounds, an initiative enabling clinicians to remotely review imaging studies with the radiologist. We describe our initial experience with virtual radiology rounds and referring provider impressions. Virtual radiology rounds, a web-based conference, use remote sharing of radiology workstations. Participants discuss imaging studies by speakerphone. Virtual radiology rounds were piloted with the Neonatal Intensive Care Unit (NICU) and the Congenital Cardiovascular Care Unit (CCVCU). Providers completed a survey assessing the perceived impact and overall value of virtual radiology rounds on patient care using a 10-point scale. Pediatric radiologists participating in virtual radiology rounds completed a survey assessing technical, educational and clinical aspects of this methodology. Sixteen providers responded to the survey; 9 NICU and 7 CCVCU staff (physicians, nurse practitioners and fellows). Virtual radiology rounds occurred 4-5 sessions/week with an average of 6.4 studies. Clinicians rated confidence in their own image interpretation with a 7.4 average rating for NICU and 7.5 average rating for CCVCU. Clinicians unanimously rated virtual radiology rounds as adding value. NICU staff preferred virtual radiology rounds to traditional rounds and CCVCU staff supported their new participation in virtual radiology rounds. Four of the five pediatric radiologists participating in virtual radiology rounds responded to the survey reporting virtual radiology rounds to be easy to facilitate (average rating: 9.3), to moderately impact interpretation of imaging studies (average rating: 6), and to provide substantial educational value for radiologists (average rating: 8.3). All pediatric radiologists felt strongly that virtual radiology rounds enable increased integration of the radiologist into the clinical care team (average rating: 8.8). Virtual radiology rounds are a
Virtual radiology rounds: adding value in the digital era
Energy Technology Data Exchange (ETDEWEB)
Fefferman, Nancy R.; Strubel, Naomi A.; Prithiani, Chandan; Chakravarti, Sujata; Caprio, Martha; Recht, Michael P. [New York University School of Medicine, Department of Radiology, New York, NY (United States)
2016-11-15
To preserve radiology rounds in the changing health care environment, we have introduced virtual radiology rounds, an initiative enabling clinicians to remotely review imaging studies with the radiologist. We describe our initial experience with virtual radiology rounds and referring provider impressions. Virtual radiology rounds, a web-based conference, use remote sharing of radiology workstations. Participants discuss imaging studies by speakerphone. Virtual radiology rounds were piloted with the Neonatal Intensive Care Unit (NICU) and the Congenital Cardiovascular Care Unit (CCVCU). Providers completed a survey assessing the perceived impact and overall value of virtual radiology rounds on patient care using a 10-point scale. Pediatric radiologists participating in virtual radiology rounds completed a survey assessing technical, educational and clinical aspects of this methodology. Sixteen providers responded to the survey; 9 NICU and 7 CCVCU staff (physicians, nurse practitioners and fellows). Virtual radiology rounds occurred 4-5 sessions/week with an average of 6.4 studies. Clinicians rated confidence in their own image interpretation with a 7.4 average rating for NICU and 7.5 average rating for CCVCU. Clinicians unanimously rated virtual radiology rounds as adding value. NICU staff preferred virtual radiology rounds to traditional rounds and CCVCU staff supported their new participation in virtual radiology rounds. Four of the five pediatric radiologists participating in virtual radiology rounds responded to the survey reporting virtual radiology rounds to be easy to facilitate (average rating: 9.3), to moderately impact interpretation of imaging studies (average rating: 6), and to provide substantial educational value for radiologists (average rating: 8.3). All pediatric radiologists felt strongly that virtual radiology rounds enable increased integration of the radiologist into the clinical care team (average rating: 8.8). Virtual radiology rounds are a
Virtual Hematoxylin and Eosin Transillumination Microscopy Using Epi-Fluorescence Imaging.
Giacomelli, Michael G; Husvogt, Lennart; Vardeh, Hilde; Faulkner-Jones, Beverly E; Hornegger, Joachim; Connolly, James L; Fujimoto, James G
2016-01-01
We derive a physically realistic model for the generation of virtual transillumination, white light microscopy images using epi-fluorescence measurements from thick, unsectioned tissue. We demonstrate this technique by generating virtual transillumination H&E images of unsectioned human breast tissue from epi-fluorescence multiphoton microscopy data. The virtual transillumination algorithm is shown to enable improved contrast and color accuracy compared with previous color mapping methods. Finally, we present an open source implementation of the algorithm in OpenGL, enabling real-time GPU-based generation of virtual transillumination microscopy images using conventional fluorescence microscopy systems.
FTree query construction for virtual screening: a statistical analysis.
Gerlach, Christof; Broughton, Howard; Zaliani, Andrea
2008-02-01
FTrees (FT) is a known chemoinformatic tool able to condense molecular descriptions into a graph object and to search for actives in large databases using graph similarity. The query graph is classically derived from a known active molecule, or a set of actives, for which a similar compound has to be found. Recently, FT similarity has been extended to fragment space, widening its capabilities. If a user were able to build a knowledge-based FT query from information other than a known active structure, the similarity search could be combined with other, normally separate, fields like de-novo design or pharmacophore searches. With this aim in mind, we performed a comprehensive analysis of several databases in terms of FT description and provide a basic statistical analysis of the FT spaces so far at hand. Vendors' catalogue collections and MDDR as a source of potential or known "actives", respectively, have been used. With the results reported herein, a set of ranges, mean values and standard deviations for several query parameters are presented in order to set a reference guide for the users. Applications on how to use this information in FT query building are also provided, using a newly built 3D-pharmacophore from 57 5HT-1F agonists and a published one which was used for virtual screening for tRNA-guanine transglycosylase (TGT) inhibitors.
When Rural Reality Goes Virtual.
Husain, Dilshad D.
1998-01-01
In rural towns where sparse population and few business are barriers, virtual reality may be the only way to bring work-based learning to students. A partnership between a small-town high school, the Ohio Supercomputer Center, and a high-tech business will enable students to explore the workplace using virtual reality. (JOW)
Shibi, Indira G; Aswathy, Lilly; Jisha, Radhakrishnan S; Masand, Vijay H; Gajbhiye, Jayant M
2016-01-01
Malaria parasites show resistance to most of the antimalarial drugs and hence developing antimalarials which can act on multitargets rather than a single target will be a promising strategy of drug design. Here we report a new approach by which virtual screening of 292 unique phytochemicals present in 72 traditionally important herbs is used for finding out inhibitors of plasmepsin-2 and falcipain-2 for antimalarial activity against P. falciparum. Initial screenings of the selected molecules by Random Forest algorithm model of Weka using the bioassay datasets AID 504850 and AID 2302 screened 120 out of the total 292 phytochemicals to be active against the targets. Toxtree scan cautioned 21 compounds to be either carcinogenic or mutagenic and were thus removed for further analysis. Out of the remaining 99 compounds, only 46 compounds offered drug-likeness as per the 'rule of five' criteria. Out of ten antimalarial drug targets, only two target proteins such as 3BPF and 3PNR of falcipain-2 and 1PFZ and 2BJU of plasmepsin-2 are selected as targets. The potential binding of the selected 46 compounds to the active sites of these four targets was analyzed using MOE software. The docked conformations and the interactions with the binding pocket residues of the target proteins were understood by 'Ligplot' analysis. It has been found that 8 compounds are dual inhibitors of falcipain-2 and plasmepsin-2, with the best binding energies. Compound 117 (6aR, 12aS)-12a-Hydroxy-9-methoxy-2,3-dimethylenedioxy-8-prenylrotenone (Usaratenoid C) present in the plant Millettia usaramensis showed maximum molecular docking score.
Investigating multimodal communication in virtual meetings
DEFF Research Database (Denmark)
Persson, John Stouby; Mathiassen, Lars
2014-01-01
recordings of their oral exchanges and video recordings of their shared dynamic representation of the project’s status and plans, our analysis reveals how their interrelating of visual and verbal communication acts enabled effective communication and coordination. In conclusion, we offer theoretical......To manage distributed work, organizations increasingly rely on virtual meetings based on multimodal, synchronous communication technologies. However, despite technological advances, it is still challenging to coordinate knowledge through these meetings with spatial and cultural separation. Against...... propositions that explain how interrelating of verbal and visual acts based on shared dynamic representations enable communication repairs during virtual meetings. We argue the proposed framework provides researchers with a novel and practical approach to investigate the complex data involved in virtual...
Directory of Open Access Journals (Sweden)
Abolhassan Naghibi
2016-03-01
Full Text Available Background and Purpose: Cervical cancer is the most prevalent cancer among women in the world. Cervical cancer is no symptoms and can be treated if diagnosed in the first stage of the disease. The aim of this study was to survey the affecting factors of the Pap smears test on perceptual factors, enabling and reinforcing (PEN-3 model constructs in women. Materials and Methods: This study was a descriptive cross-sectional study. The sample size was 416 married women with random sampling. The questionnaire had 50 questions based on PEN-3 model structures. Data were analyzed by descriptive statistics and logistic regression method in software SPSS 20. Results: The mean age of women was 32.70 ± 21.00 years. The knowledge of risk factors and screening methods for cervical cancer was 37.2. About 40% of women had a history of Pap smears. The most important of perception factors were effective, family history of the disease, encourage people to Pap smear, and fear of detecting of cervical cancer. The most important enabling factors were the presence of expert health personnel to provide training and Pap smear test (50.3%, lack of time and too busy to do Pap smear test (23.2%. The reinforcing factors were the media advice (41.3%, doctor’s advice (32.5% and neglect and forgetfulness (36.2%. Conclusion: This study has shown the Pap smear screening behavior affected by personal factors, family, cultural and economic. Application of PEN-3 can effective in planning and designing intervention programs for cervical cancer screening.
Discovery of Natural Products as Novel and Potent FXR Antagonists by Virtual Screening
Diao, Yanyan; Jiang, Jing; Zhang, Shoude; Li, Shiliang; Shan, Lei; Huang, Jin; Zhang, Weidong; Li, Honglin
2018-04-01
Farnesoid X receptor (FXR) is a member of nuclear receptor family involved in multiple physiological processes through regulating specific target genes. The critical role of FXR as a transcriptional regulator makes it a promising target for diverse diseases, especially those related to metabolic disorders such as diabetes and cholestasis. However, the underlying activation mechanism of FXR is still a blur owing to the absence of proper FXR modulators. To identify potential FXR modulators, an in-house natural product database (NPD) containing over 4000 compounds was screened by structure-based virtual screening strategy and subsequent hit-based similarity searching method. After the yeast two-hybrid (Y2H) assay, six natural products were identified as FXR antagonists which blocked the CDCA-induced SRC-1 association. The IC50 values of compounds 2a, a diterpene bearing polycyclic skeleton, and 3a, named daphneone with chain scaffold, are as low as 1.29 μM and 1.79 μM, respectively. Compared to the control compound guggulsterone (IC50 = 6.47 μM), compounds 2a and 3a displayed 5-fold and 3-fold higher antagonistic activities against FXR, respectively. Remarkably, the two representative compounds shared low topological similarities with other reported FXR antagonists. According to the putative binding poses, the molecular basis of these antagonists against FXR was also elucidated in this report.
Patel, Shivani; Modi, Palmi; Chhabria, Mahesh
2018-05-01
Caspase-1 is a key endoprotease responsible for the post-translational processing of pro-inflammatory cytokines IL-1β, 18 & 33. Excessive secretion of IL-1β leads to numerous inflammatory and autoimmune diseases. Thus caspase-1 inhibition would be considered as an important therapeutic strategy for development of newer anti-inflammatory agents. Here we have employed an integrated virtual screening by combining pharmacophore mapping and docking to identify small molecules as caspase-1 inhibitors. The ligand based 3D pharmacophore model was generated having the essential structural features of (HBA, HY & RA) using a data set of 27 compounds. A validated pharmacophore hypothesis (Hypo 1) was used to screen ZINC and Minimaybridge chemical databases. The retrieved virtual hits were filtered by ADMET properties and molecular docking analysis. Subsequently, the cross-docking study was also carried out using crystal structure of caspase-1, 3, 7 and 8 to identify the key residual interaction for specific caspase-1 inhibition. Finally, the best mapped and top scored (ZINC00885612, ZINC72003647, BTB04175 and BTB04410) molecules were subjected to molecular dynamics simulation for accessing the dynamic structure of protein after ligand binding. This study identifies the most promising hits, which can be leads for the development of novel caspase-1 inhibitors as anti-inflammatory agents. Copyright © 2018 Elsevier Inc. All rights reserved.
A Virtual Commissioning Learning Platform
DEFF Research Database (Denmark)
Mortensen, Steffen; Madsen, Ole
2018-01-01
The introduction of reconfigurable manufacturing systems (RMS), Industry 4.0 and the associated technologies requires the establishment of new competencies. Towards that goal, Aalborg University (AAU) has developed an Industry 4.0 learning factory, the AAU Smart Production Lab. The AAU Smart...... Production Lab integrates a number of Industry 4.0 technologies for learning and research purposes. One of the many techniques is virtual commissioning. Virtual commissioning uses a virtual plant model and real controllers (PLCs) enabling a full emulation of the manufacturing system for verification. Virtual...... commissioning can lower the commissioning time up to 63%, allowing faster time to market. However, virtual commission is still missing industrial impact one of the reasons being lack of competencies and integration experiences. The paper presents the setup of the virtual commissioning learning platform...
Virtual Hematoxylin and Eosin Transillumination Microscopy Using Epi-Fluorescence Imaging.
Directory of Open Access Journals (Sweden)
Michael G Giacomelli
Full Text Available We derive a physically realistic model for the generation of virtual transillumination, white light microscopy images using epi-fluorescence measurements from thick, unsectioned tissue. We demonstrate this technique by generating virtual transillumination H&E images of unsectioned human breast tissue from epi-fluorescence multiphoton microscopy data. The virtual transillumination algorithm is shown to enable improved contrast and color accuracy compared with previous color mapping methods. Finally, we present an open source implementation of the algorithm in OpenGL, enabling real-time GPU-based generation of virtual transillumination microscopy images using conventional fluorescence microscopy systems.
Virtual Proprioception for eccentric training.
LeMoyne, Robert; Mastroianni, Timothy
2017-07-01
Wireless inertial sensors enable quantified feedback, which can be applied to evaluate the efficacy of therapy and rehabilitation. In particular eccentric training promotes a beneficial rehabilitation and strength training strategy. Virtual Proprioception for eccentric training applies real-time feedback from a wireless gyroscope platform enabled through a software application for a smartphone. Virtual Proprioception for eccentric training is applied to the eccentric phase of a biceps brachii strength training and contrasted to a biceps brachii strength training scenario without feedback. During the operation of Virtual Proprioception for eccentric training the intent is to not exceed a prescribed gyroscope signal threshold based on the real-time presentation of the gyroscope signal, in order to promote the eccentric aspect of the strength training endeavor. The experimental trial data is transmitted wireless through connectivity to the Internet as an email attachment for remote post-processing. A feature set is derived from the gyroscope signal for machine learning classification of the two scenarios of Virtual Proprioception real-time feedback for eccentric training and eccentric training without feedback. Considerable classification accuracy is achieved through the application of a multilayer perceptron neural network for distinguishing between the Virtual Proprioception real-time feedback for eccentric training and eccentric training without feedback.
Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge
Kumar, Ashutosh; Zhang, Kam Y. J.
2012-05-01
SAMPL3 fragment based virtual screening challenge provides a valuable opportunity for researchers to test their programs, methods and screening protocols in a blind testing environment. We participated in SAMPL3 challenge and evaluated our virtual fragment screening protocol, which involves RosettaLigand as the core component by screening a 500 fragments Maybridge library against bovine pancreatic trypsin. Our study reaffirmed that the real test for any virtual screening approach would be in a blind testing environment. The analyses presented in this paper also showed that virtual screening performance can be improved, if a set of known active compounds is available and parameters and methods that yield better enrichment are selected. Our study also highlighted that to achieve accurate orientation and conformation of ligands within a binding site, selecting an appropriate method to calculate partial charges is important. Another finding is that using multiple receptor ensembles in docking does not always yield better enrichment than individual receptors. On the basis of our results and retrospective analyses from SAMPL3 fragment screening challenge we anticipate that chances of success in a fragment screening process could be increased significantly with careful selection of receptor structures, protein flexibility, sufficient conformational sampling within binding pocket and accurate assignment of ligand and protein partial charges.
Machinima interventions: innovative approaches to immersive virtual world curriculum integration
Directory of Open Access Journals (Sweden)
Andrew John Middleton
2008-12-01
Full Text Available The educational value of Immersive Virtual Worlds (IVWs seems to be in their social immersive qualities and as an accessible simulation technology. In contrast to these synchronous applications this paper discusses the use of educational machinima developed in IVW virtual film sets. It also introduces the concept of media intervention, proposing that digital media works best when simply developed for deployment within a blended curriculum to inform learning activity, and where the media are specifically designed to set challenges, seed ideas, or illustrate problems. Machinima, digital films created in IVWs, or digital games offer a rich mechanism for delivering such interventions. Scenes are storyboarded, constructed, shot and edited using techniques similar to professional film production, drawing upon a cast of virtual world avatars controlled through a human–computer interface, rather than showing real-life actors. The approach enables academics or students to make films using screen capture software and desktop editing tools. In student-generated production models the learning value may be found in the production process itself. This paper discusses six case studies and several themes from research on ideas for educational machinima including: access to production; creativity in teaching and learning; media intervention methodology; production models; reusability; visualisation and simulation.
CamMedNP: building the Cameroonian 3D structural natural products database for virtual screening.
Ntie-Kang, Fidele; Mbah, James A; Mbaze, Luc Meva'a; Lifongo, Lydia L; Scharfe, Michael; Hanna, Joelle Ngo; Cho-Ngwa, Fidelis; Onguéné, Pascal Amoa; Owono Owono, Luc C; Megnassan, Eugene; Sippl, Wolfgang; Efange, Simon M N
2013-04-16
Computer-aided drug design (CADD) often involves virtual screening (VS) of large compound datasets and the availability of such is vital for drug discovery protocols. We present CamMedNP - a new database beginning with more than 2,500 compounds of natural origin, along with some of their derivatives which were obtained through hemisynthesis. These are pure compounds which have been previously isolated and characterized using modern spectroscopic methods and published by several research teams spread across Cameroon. In the present study, 224 distinct medicinal plant species belonging to 55 plant families from the Cameroonian flora have been considered. About 80 % of these have been previously published and/or referenced in internationally recognized journals. For each compound, the optimized 3D structure, drug-like properties, plant source, collection site and currently known biological activities are given, as well as literature references. We have evaluated the "drug-likeness" of this database using Lipinski's "Rule of Five". A diversity analysis has been carried out in comparison with the ChemBridge diverse database. CamMedNP could be highly useful for database screening and natural product lead generation programs.
Jiang, Tianyu; Zhu, Peng; Du, Lupei; Li, Minyong
2018-01-01
Quorum sensing (QS) is a cell-to-cell communication system that regulates gene expression as a result of the production and perception of signal molecules called autoinducers (AIs). AI-2 is a QS autoinducer produced by both Gram-negative and Gram-positive bacteria, in which it regulates intraspecies and interspecies communication. The identification of QS inhibitors is considered a promising strategy for the development of anti-virulence drugs with reduced selective pressure for resistance. Here we describe a high-throughput virtual screening approach to identify AI-2 quorum sensing inhibitors on the basis of Vibrio harveyi LuxPQ crystal structure. Seven potent inhibitors with IC 50 values in the micromolar range were selected with no effect or low effect on V. harveyi growth rate.
Bowser, D; Marqusee, H; El Koussa, M; Atun, R
2017-11-01
To identify barriers and enablers that impact access to early screening, detection, and diagnosis of breast cancer both globally and more specifically in the Middle East and North Africa (MENA) region (with a specific focus on Egypt, Jordan, Oman, Saudi Arabia, United Arab Emirates [UAE], and Kuwait) with a specific focus on the health system. A systematic review of literature. We conducted a systematic reviewing using the PRISMA methodology. We searched PubMed, Global Index Medicus, and EMBASE for studies on 'breast cancer', 'breast neoplasm,' or 'screening, early detection, and early diagnosis' as well as key words related to the following barriers: religion, culture, health literacy, lack of knowledge/awareness/understanding, attitudes, fatalism/fear, shame/embarrassment, and physician gender from January 1, 2000 until September 1, 2016. Two independent reviewers screened both titles and abstracts. The application of inclusion and exclusion criteria yielded a final list of articles. A conceptual framework was used to guide the thematic analysis and examine health system barriers and enablers to breast cancer screening at the broader macro health system level, at the health provider level, and the individual level. The analysis was conducted globally and in the MENA region. A total of 11,936 references were identified through the initial search strategy, of which 55 were included in the final thematic analysis. The results found the following barriers and enablers to access to breast cancer screening at the health system level, the health provider level, and the individual level: health system structures such as health insurance and care coordination systems, costs, time concerns, provider characteristics including gender of the provider, quality of care issues, medical concerns, and fear. In addition, the following seven barriers and enablers were identified at the health system or provider level as significantly impacting screening for breast cancer: (1) access
Virtual NC machine model with integrated knowledge data
International Nuclear Information System (INIS)
Sidorenko, Sofija; Dukovski, Vladimir
2002-01-01
The concept of virtual NC machining was established for providing a virtual product that could be compared with an appropriate designed product, in order to make NC program correctness evaluation, without real experiments. This concept is applied in the intelligent CAD/CAM system named VIRTUAL MANUFACTURE. This paper presents the first intelligent module that enables creation of the virtual models of existed NC machines and virtual creation of new ones, applying modular composition. Creation of a virtual NC machine is carried out via automatic knowledge data saving (features of the created NC machine). (Author)
Directory of Open Access Journals (Sweden)
Pablo Andrei Nogara
2015-01-01
Full Text Available Alzheimer’s disease (AD is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acetylcholine (ACh in the brain by using acetylcholinesterase inhibitors (AChEIs. In this study, we used the ZINC databank and the Lipinski’s rule of five to perform a virtual screening and a molecular docking (using Auto Dock Vina 1.1.1 aiming to select possible compounds that have quaternary ammonium atom able to inhibit acetylcholinesterase (AChE activity. The molecules were obtained by screening and further in vitro assays were performed to analyze the most potent inhibitors through the IC50 value and also to describe the interaction models between inhibitors and enzyme by molecular docking. The results showed that compound D inhibited AChE activity from different vertebrate sources and butyrylcholinesterase (BChE from Equus ferus (EfBChE, with IC50 ranging from 1.69 ± 0.46 to 5.64 ± 2.47 µM. Compound D interacted with the peripheral anionic subsite in both enzymes, blocking substrate entrance to the active site. In contrast, compound C had higher specificity as inhibitor of EfBChE. In conclusion, the screening was effective in finding inhibitors of AChE and BuChE from different organisms.
Litfin, Thomas; Zhou, Yaoqi; Yang, Yuedong
2017-04-15
The high cost of drug discovery motivates the development of accurate virtual screening tools. Binding-homology, which takes advantage of known protein-ligand binding pairs, has emerged as a powerful discrimination technique. In order to exploit all available binding data, modelled structures of ligand-binding sequences may be used to create an expanded structural binding template library. SPOT-Ligand 2 has demonstrated significantly improved screening performance over its previous version by expanding the template library 15 times over the previous one. It also performed better than or similar to other binding-homology approaches on the DUD and DUD-E benchmarks. The server is available online at http://sparks-lab.org . yaoqi.zhou@griffith.edu.au or yuedong.yang@griffith.edu.au. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
A Cross-Disciplinary Literature Review: Examining Trust on Virtual Teams
Berry, Gregory R.
2011-01-01
Effective and efficient teams communicate, collaborate, and perform, even if these teams are not co-located. Although much is known about enabling effectiveness on face-to-face teams, considerably less is known about similarly enabling effectiveness on virtual teams. Yet the use of virtual teams is common and will likely become more commonplace as…
Creating Virtual-hand and Virtual-face Illusions to Investigate Self-representation.
Ma, Ke; Lippelt, Dominique P; Hommel, Bernhard
2017-03-01
Studies investigating how people represent themselves and their own body often use variants of "ownership illusions", such as the traditional rubber-hand illusion or the more recently discovered enfacement illusion. However, these examples require rather artificial experimental setups, in which the artificial effector needs to be stroked in synchrony with the participants' real hand or face-a situation in which participants have no control over the stroking or the movements of their real or artificial effector. Here, we describe a technique to establish ownership illusions in a setup that is more realistic, more intuitive, and of presumably higher ecological validity. It allows creating the virtual-hand illusion by having participants control the movements of a virtual hand presented on a screen or in virtual space in front of them. If the virtual hand moves in synchrony with the participants' own real hand, they tend to perceive the virtual hand as part of their own body. The technique also creates the virtual-face illusion by having participants control the movements of a virtual face in front of them, again with the effect that they tend to perceive the face as their own if it moves in synchrony with their real face. Studying the circumstances that illusions of this sort can be created, increased, or reduced provides important information about how people create and maintain representations of themselves.
Energy Technology Data Exchange (ETDEWEB)
2016-11-18
There is a lack of state-of-the-art HPC simulation tools for simulating general quantum computing. Furthermore, there are no real software tools that integrate current quantum computers into existing classical HPC workflows. This product, the Quantum Virtual Machine (QVM), solves this problem by providing an extensible framework for pluggable virtual, or physical, quantum processing units (QPUs). It enables the execution of low level quantum assembly codes and returns the results of such executions.
Directory of Open Access Journals (Sweden)
Ahsan Kareem
2017-08-01
Full Text Available Despite many advances in the area of wind effects on structures in recent decades, research has been traditionally conducted within limited resources scattered geographically. With the trend toward increasingly complex designs of civil infrastructure combined with the escalating potential for losses by extreme wind events, a new culture of research needs to be established based on innovative and collaborative solutions for better management of the impact of extreme wind events. To address this change, this paper presents a new paradigm of a multiscale cyber-based laboratory framework for the analysis/design, modeling, and simulation of wind load effects based on an ongoing collaborative cyberinfrastructure-based platform, Virtual Organization for Reducing the Toll of EXtreme Winds (VORTEX-Winds, https://vortex-winds.org, and discusses its current status since its inception in 2007 and ongoing developments. This collaborative framework as it evolves would enable a paradigm shift by offering advanced cyber-enabled modules (e-modules for accelerating advances in research and education to achieve improved understanding and better modeling of wind effects on structures. Accordingly, it will enhance wind community’s analysis and design capabilities to address next-generation challenges posed by wind. Through empowering those without computational or experimental resources, the e-modules will encompass a large set of subject areas and topics categorized as Database-enabled design, Full-scale/Field site data repository, Statistical/Stochastic toolboxes, Tele-experimentation, Uncertainty modeling, Damage assessment, and Computational platforms. This prototype will allow access to the individual e-module, while it is envisaged that next level of development in VORTEX-Winds will have the capability for an automated and integrated analysis/design through a nexus of e-modules. A highlight of the e-modules currently completed or in development is presented
Virtual Reality in the Medical Field
Motomatsu, Haruka
2014-01-01
The objective is to analyze the use of the emerging 3D computer technology of VirtualReality in the use of relieving pain in physically impaired conditions such as burn victims,amputees, and phantom limb patients, during therapy and medical procedures. Virtualtechnology generates a three dimensional visual virtual world in which enables interaction.Comparison will be made between the emerging technology of the Virtual Reality and methodsusually used, which are the use of medicine. Medicine ha...
Ericksen, Spencer S; Wu, Haozhen; Zhang, Huikun; Michael, Lauren A; Newton, Michael A; Hoffmann, F Michael; Wildman, Scott A
2017-07-24
In structure-based virtual screening, compound ranking through a consensus of scores from a variety of docking programs or scoring functions, rather than ranking by scores from a single program, provides better predictive performance and reduces target performance variability. Here we compare traditional consensus scoring methods with a novel, unsupervised gradient boosting approach. We also observed increased score variation among active ligands and developed a statistical mixture model consensus score based on combining score means and variances. To evaluate performance, we used the common performance metrics ROCAUC and EF1 on 21 benchmark targets from DUD-E. Traditional consensus methods, such as taking the mean of quantile normalized docking scores, outperformed individual docking methods and are more robust to target variation. The mixture model and gradient boosting provided further improvements over the traditional consensus methods. These methods are readily applicable to new targets in academic research and overcome the potentially poor performance of using a single docking method on a new target.
Moyer-Packenham, Patricia S.; Bullock, Emma K.; Shumway, Jessica F.; Tucker, Stephen I.; Watts, Christina M.; Westenskow, Arla; Anderson-Pence, Katie L.; Maahs-Fladung, Cathy; Boyer-Thurgood, Jennifer; Gulkilik, Hilal; Jordan, Kerry
2016-03-01
This paper focuses on understanding the role that affordances played in children's learning performance and efficiency during clinical interviews of their interactions with mathematics apps on touch-screen devices. One hundred children, ages 3 to 8, each used six different virtual manipulative mathematics apps during 30-40-min interviews. The study used a convergent mixed methods design, in which quantitative and qualitative data were collected concurrently to answer the research questions (Creswell and Plano Clark 2011). Videos were used to capture each child's interactions with the virtual manipulative mathematics apps, document learning performance and efficiency, and record children's interactions with the affordances within the apps. Quantitized video data answered the research question on differences in children's learning performance and efficiency between pre- and post-assessments. A Wilcoxon matched pairs signed-rank test was used to explore these data. Qualitative video data was used to identify affordance access by children when using each app, identifying 95 potential helping and hindering affordances among the 18 apps. The results showed that there were changes in children's learning performance and efficiency when children accessed a helping or a hindering affordance. Helping affordances were more likely to be accessed by children who progressed between the pre- and post-assessments, and the same affordances had helping and hindering effects for different children. These results have important implications for the design of virtual manipulative mathematics learning apps.
Cooperation, Coordination, and Trust in Virtual Teams: Insights from Virtual Games
Korsgaard, M. Audrey; Picot, Arnold; Wigand, Rolf T.; Welpe, Isabelle M.; Assmann, Jakob J.
This chapter considers fundamental concepts of effective virtual teams, illustrated by research on Travian, a massively multiplayer online strategy game wherein players seek to build empires. Team inputs are the resources that enable individuals to work interdependently toward a common goal, including individual and collective capabilities, shared knowledge structures, and leadership style. Team processes, notably coordination and cooperation, transform team inputs to desired collective outcomes. Because the members of virtual teams are geographically dispersed, relying on information and communication technology, three theories are especially relevant for understanding how they can function effectively: social presence theory, media richness theory, and media synchronicity theory. Research in settings like Travian can inform our understanding of structures, processes, and performance of virtual teams. Such research could provide valuable insight into the emergence and persistence of trust and cooperation, as well as the impact of different communication media for coordination and information management in virtual organizations.
Low cost heads-up virtual reality (HUVR) with optical tracking and haptic feedback
Margolis, Todd
2011-01-23
Researchers at the University of California, San Diego, have created a new, relatively low-cost augmented reality system that enables users to touch the virtual environment they are immersed in. The Heads-Up Virtual Reality device (HUVR) couples a consumer 3D HD flat screen TV with a half-silvered mirror to project any graphic image onto the user\\'s hands and into the space surrounding them. With his or her head position optically tracked to generate the correct perspective view, the user maneuvers a force-feedback (haptic) device to interact with the 3D image, literally \\'touching\\' the object\\'s angles and contours as if it was a tangible physical object. HUVR can be used for training and education in structural and mechanical engineering, archaeology and medicine as well as other tasks that require hand-eye coordination. One of the most unique characteristics of HUVR is that a user can place their hands inside of the virtual environment without occluding the 3D image. Built using open-source software and consumer level hardware, HUVR offers users a tactile experience in an immersive environment that is functional, affordable and scalable.
Low cost heads-up virtual reality (HUVR) with optical tracking and haptic feedback
Margolis, Todd; DeFanti, Thomas A.; Dawe, Greg; Prudhomme, Andrew; Schulze, Jurgen P.; Cutchin, Steve
2011-03-01
Researchers at the University of California, San Diego, have created a new, relatively low-cost augmented reality system that enables users to touch the virtual environment they are immersed in. The Heads-Up Virtual Reality device (HUVR) couples a consumer 3D HD flat screen TV with a half-silvered mirror to project any graphic image onto the user's hands and into the space surrounding them. With his or her head position optically tracked to generate the correct perspective view, the user maneuvers a force-feedback (haptic) device to interact with the 3D image, literally 'touching' the object's angles and contours as if it was a tangible physical object. HUVR can be used for training and education in structural and mechanical engineering, archaeology and medicine as well as other tasks that require hand-eye coordination. One of the most unique characteristics of HUVR is that a user can place their hands inside of the virtual environment without occluding the 3D image. Built using open-source software and consumer level hardware, HUVR offers users a tactile experience in an immersive environment that is functional, affordable and scalable.
VIRTUALIZATION TECHNICAL THINKING WITHIN THE INFORMATION TECHNOLOGY
Directory of Open Access Journals (Sweden)
Robert Lis
2014-11-01
Full Text Available The article presents the possibilities of virtualization technical thinking within the information technology. This question expresses the need for virtualization of existing information systems to improve the conduct of business by the company. In resulting virtualization of the technical-computer thought on against existing needs of the functioning of 16-bit systems in 64-bit systems. Enables cost-effective use of excess capacity existing computing resources.
Game-Based Virtual Worlds as Decentralized Virtual Activity Systems
Scacchi, Walt
There is widespread interest in the development and use of decentralized systems and virtual world environments as possible new places for engaging in collaborative work activities. Similarly, there is widespread interest in stimulating new technological innovations that enable people to come together through social networking, file/media sharing, and networked multi-player computer game play. A decentralized virtual activity system (DVAS) is a networked computer supported work/play system whose elements and social activities can be both virtual and decentralized (Scacchi et al. 2008b). Massively multi-player online games (MMOGs) such as World of Warcraft and online virtual worlds such as Second Life are each popular examples of a DVAS. Furthermore, these systems are beginning to be used for research, deve-lopment, and education activities in different science, technology, and engineering domains (Bainbridge 2007, Bohannon et al. 2009; Rieber 2005; Scacchi and Adams 2007; Shaffer 2006), which are also of interest here. This chapter explores two case studies of DVASs developed at the University of California at Irvine that employ game-based virtual worlds to support collaborative work/play activities in different settings. The settings include those that model and simulate practical or imaginative physical worlds in different domains of science, technology, or engineering through alternative virtual worlds where players/workers engage in different kinds of quests or quest-like workflows (Jakobsson 2006).
Final Report: Enabling Exascale Hardware and Software Design through Scalable System Virtualization
Energy Technology Data Exchange (ETDEWEB)
Bridges, Patrick G.
2015-02-01
In this grant, we enhanced the Palacios virtual machine monitor to increase its scalability and suitability for addressing exascale system software design issues. This included a wide range of research on core Palacios features, large-scale system emulation, fault injection, perfomrance monitoring, and VMM extensibility. This research resulted in large number of high-impact publications in well-known venues, the support of a number of students, and the graduation of two Ph.D. students and one M.S. student. In addition, our enhanced version of the Palacios virtual machine monitor has been adopted as a core element of the Hobbes operating system under active DOE-funded research and development.
Semantically Enabling Knowledge Representation of Metamorphic Petrology Data
West, P.; Fox, P. A.; Spear, F. S.; Adali, S.; Nguyen, C.; Hallett, B. W.; Horkley, L. K.
2012-12-01
More and more metamorphic petrology data is being collected around the world, and is now being organized together into different virtual data portals by means of virtual organizations. For example, there is the virtual data portal Petrological Database (PetDB, http://www.petdb.org) of the Ocean Floor that is organizing scientific information about geochemical data of ocean floor igneous and metamorphic rocks; and also The Metamorphic Petrology Database (MetPetDB, http://metpetdb.rpi.edu) that is being created by a global community of metamorphic petrologists in collaboration with software engineers and data managers at Rensselaer Polytechnic Institute. The current focus is to provide the ability for scientists and researchers to register their data and search the databases for information regarding sample collections. What we present here is the next step in evolution of the MetPetDB portal, utilizing semantically enabled features such as discovery, data casting, faceted search, knowledge representation, and linked data as well as organizing information about the community and collaboration within the virtual community itself. We take the information that is currently represented in a relational database and make it available through web services, SPARQL endpoints, semantic and triple-stores where inferencing is enabled. We will be leveraging research that has taken place in virtual observatories, such as the Virtual Solar Terrestrial Observatory (VSTO) and the Biological and Chemical Oceanography Data Management Office (BCO-DMO); vocabulary work done in various communities such as Observations and Measurements (ISO 19156), FOAF (Friend of a Friend), Bibo (Bibliography Ontology), and domain specific ontologies; enabling provenance traces of samples and subsamples using the different provenance ontologies; and providing the much needed linking of data from the various research organizations into a common, collaborative virtual observatory. In addition to better
DEFF Research Database (Denmark)
Simmons, Katie J; Gotfryd, Kamil; Billesbølle, Christian B
2013-01-01
Abstract Membrane proteins are intrinsically involved in both human and pathogen physiology, and are the target of 60% of all marketed drugs. During the past decade, advances in the studies of membrane proteins using X-ray crystallography, electron microscopy and NMR-based techniques led to the e...... this is a virtual high-throughput screening (vHTS) technique initially developed for soluble proteins. This paper describes application of this technique to the discovery of inhibitors of the leucine transporter (LeuT), a member of the neurotransmitter:sodium symporter (NSS) family....
International Nuclear Information System (INIS)
Wayne, R.A.
1997-01-01
The primary responsibility of an intrusion detection system (IDS) operator is to monitor the system, assess alarms, and summon and coordinate the response team when a threat is acknowledged. The tools currently provided to the operator are somewhat limited: monitors must be switched, keystrokes must be entered to call up intrusion sensor data, and communication with the response force must be maintained. The Virtual tower is an operator interface assembled from low-cost commercial-off-the-shelf hardware and software; it enables large amounts of data to be displayed in a virtual manner that provides instant recognition for the operator and increases assessment accuracy in alarm annunciator and control systems. This is accomplished by correlating and fusing the data into a 360-degree visual representation that employs color, auxiliary attributes, video, and directional audio to prompt the operator. The Virtual Tower would be a valuable low-cost enhancement to existing systems
Telehealth solutions to enable global collaboration in rheumatic heart disease screening.
Lopes, Eduardo Lv; Beaton, Andrea Z; Nascimento, Bruno R; Tompsett, Alison; Dos Santos, Julia Pa; Perlman, Lindsay; Diamantino, Adriana C; Oliveira, Kaciane Kb; Oliveira, Cassio M; Nunes, Maria do Carmo P; Bonisson, Leonardo; Ribeiro, Antônio Lp; Sable, Craig
2018-02-01
Background The global burden of rheumatic heart disease is nearly 33 million people. Telemedicine, using cloud-server technology, provides an ideal solution for sharing images performed by non-physicians with cardiologists who are experts in rheumatic heart disease. Objective We describe our experience in using telemedicine to support a large rheumatic heart disease outreach screening programme in the Brazilian state of Minas Gerais. Methods The Programa de Rastreamento da Valvopatia Reumática (PROVAR) is a prospective cross-sectional study aimed at gathering epidemiological data on the burden of rheumatic heart disease in Minas Gerais and testing of a non-expert, telemedicine-supported model of outreach rheumatic heart disease screening. The primary goal is to enable expert support of remote rheumatic heart disease outreach through cloud-based sharing of echocardiographic images between Minas Gerais and Washington. Secondary goals include (a) developing and sharing online training modules for non-physicians in echocardiography performance and interpretation and (b) utilising a secure web-based system to share clinical and research data. Results PROVAR included 4615 studies that were performed by non-experts at 21 schools and shared via cloud-telemedicine technology. Latent rheumatic heart disease was found in 251 subjects (4.2% of subjects: 3.7% borderline and 0.5% definite disease). Of the studies, 50% were preformed on full functional echocardiography machines and transmitted via Digital Imaging and Communications in Medicine (DICOM) and 50% were performed on handheld echocardiography machines and transferred via a secure Dropbox connection. The average time between study performance date and interpretation was 10 days. There was 100% success in initial image transfer. Less than 1% of studies performed by non-experts could not be interpreted. Discussion A sustainable, low-cost telehealth model, using task-shifting with non-medical personal in low and middle
Developing Mixed Reality Educational Applications: The Virtual Touch Toolkit.
Mateu, Juan; Lasala, María José; Alamán, Xavier
2015-08-31
In this paper, we present Virtual Touch, a toolkit that allows the development of educational activities through a mixed reality environment such that, using various tangible elements, the interconnection of a virtual world with the real world is enabled. The main goal of Virtual Touch is to facilitate the installation, configuration and programming of different types of technologies, abstracting the creator of educational applications from the technical details involving the use of tangible interfaces and virtual worlds. Therefore, it is specially designed to enable teachers to themselves create educational activities for their students in a simple way, taking into account that teachers generally lack advanced knowledge in computer programming and electronics. The toolkit has been used to develop various educational applications that have been tested in two secondary education high schools in Spain.
Developing Mixed Reality Educational Applications: The Virtual Touch Toolkit
Mateu, Juan; Lasala, María José; Alamán, Xavier
2015-01-01
In this paper, we present Virtual Touch, a toolkit that allows the development of educational activities through a mixed reality environment such that, using various tangible elements, the interconnection of a virtual world with the real world is enabled. The main goal of Virtual Touch is to facilitate the installation, configuration and programming of different types of technologies, abstracting the creator of educational applications from the technical details involving the use of tangible interfaces and virtual worlds. Therefore, it is specially designed to enable teachers to themselves create educational activities for their students in a simple way, taking into account that teachers generally lack advanced knowledge in computer programming and electronics. The toolkit has been used to develop various educational applications that have been tested in two secondary education high schools in Spain. PMID:26334275
Binding-site assessment by virtual fragment screening.
Directory of Open Access Journals (Sweden)
Niu Huang
2010-04-01
Full Text Available The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock approximately 11,000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors.
Hardware/software virtualization for the reconfigurable multicore platform.
Ferger, M.; Al Kadi, M.; Hübner, M.; Koedam, M.L.P.J.; Sinha, S.S.; Goossens, K.G.W.; Marchesan Almeida, Gabriel; Rodrigo Azambuja, J.; Becker, Juergen
2012-01-01
This paper presents the Flex Tiles approach for the virtualization of hardware and software for a reconfigurable multicore architecture. The approach enables the virtualization of a dynamic tile-based hardware architecture consisting of processing tiles connected via a network-on-chip and a
Semi-Immersive Virtual Turbine Engine Simulation System
Abidi, Mustufa H.; Al-Ahmari, Abdulrahman M.; Ahmad, Ali; Darmoul, Saber; Ameen, Wadea
2018-05-01
The design and verification of assembly operations is essential for planning product production operations. Recently, virtual prototyping has witnessed tremendous progress, and has reached a stage where current environments enable rich and multi-modal interaction between designers and models through stereoscopic visuals, surround sound, and haptic feedback. The benefits of building and using Virtual Reality (VR) models in assembly process verification are discussed in this paper. In this paper, we present the virtual assembly (VA) of an aircraft turbine engine. The assembly parts and sequences are explained using a virtual reality design system. The system enables stereoscopic visuals, surround sounds, and ample and intuitive interaction with developed models. A special software architecture is suggested to describe the assembly parts and assembly sequence in VR. A collision detection mechanism is employed that provides visual feedback to check the interference between components. The system is tested for virtual prototype and assembly sequencing of a turbine engine. We show that the developed system is comprehensive in terms of VR feedback mechanisms, which include visual, auditory, tactile, as well as force feedback. The system is shown to be effective and efficient for validating the design of assembly, part design, and operations planning.
Klann, Tyler S; Black, Joshua B; Chellappan, Malathi; Safi, Alexias; Song, Lingyun; Hilton, Isaac B; Crawford, Gregory E; Reddy, Timothy E; Gersbach, Charles A
2017-06-01
Large genome-mapping consortia and thousands of genome-wide association studies have identified non-protein-coding elements in the genome as having a central role in various biological processes. However, decoding the functions of the millions of putative regulatory elements discovered in these studies remains challenging. CRISPR-Cas9-based epigenome editing technologies have enabled precise perturbation of the activity of specific regulatory elements. Here we describe CRISPR-Cas9-based epigenomic regulatory element screening (CERES) for improved high-throughput screening of regulatory element activity in the native genomic context. Using dCas9 KRAB repressor and dCas9 p300 activator constructs and lentiviral single guide RNA libraries to target DNase I hypersensitive sites surrounding a gene of interest, we carried out both loss- and gain-of-function screens to identify regulatory elements for the β-globin and HER2 loci in human cells. CERES readily identified known and previously unidentified regulatory elements, some of which were dependent on cell type or direction of perturbation. This technology allows the high-throughput functional annotation of putative regulatory elements in their native chromosomal context.
Bioprospecting of Thermostable Cellulolytic Enzymes through Modeling and Virtual Screening Method
Directory of Open Access Journals (Sweden)
R. Navanietha Krishnaraj
2017-04-01
Full Text Available Cellulolytic enzymes are promising candidates for the use of cellulose in any bioprocess operations and for the disposal of the cellulosic wastes in an environmentally benign manner. Cellulases from thermophiles have the advantage of hydrolyzing cellulose at wider range of operating conditions unlike the normal enzymes. Herein we report the modeled structures of cellulolytic enzymes (endoglucanase, cellobiohydrolase and ß-glucosidase from a thermophilic bacterium,Clostridium thermocellumand their validation using Root Mean Square Deviation (RMSD and Ramachandran plot analyses. Further, the molecular interactions of the modeled enzyme with cellulose were analyzed using molecular docking technique. The results of molecular docking showed that the endoglucanase, cellobiohydrolase and ß-glucosidase had the binding affinities of -10.7, -9.0 and -10.8 kcal/mol, respectively. A correlation between the binding affinity of the endoglucanase with cellulose and the enzyme activity was also demonstrated. The results showed that the binding affinities of cellulases with cellulose could be used as a tool to assess the hydrolytic activity of cellulases. The results obtained could be used in virtual screening of cellulolytic enzymes based on the molecular interactions with the substrate, and aid in developing systems biology models of thermophiles for industrial biotechnology applications.
Directory of Open Access Journals (Sweden)
Wei Wang
2017-01-01
Full Text Available Chloride intracellular channel 1 (CLIC1 is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM database using structure-based virtual screening and molecular dynamics (MD simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition.
Zhao, Yongli; Hu, Liyazhou; Wang, Wei; Li, Yajie; Zhang, Jie
2017-01-01
With the continuous opening of resource acquisition and application, there are a large variety of network hardware appliances deployed as the communication infrastructure. To lunch a new network application always implies to replace the obsolete devices and needs the related space and power to accommodate it, which will increase the energy and capital investment. Network function virtualization1 (NFV) aims to address these problems by consolidating many network equipment onto industry standard elements such as servers, switches and storage. Many types of IT resources have been deployed to run Virtual Network Functions (vNFs), such as virtual switches and routers. Then how to deploy NFV in optical transport networks is a of great importance problem. This paper focuses on this problem, and gives an implementation architecture of NFV-enabled optical transport networks based on Software Defined Optical Networking (SDON) with the procedure of vNFs call and return. Especially, an implementation solution of NFV-enabled optical transport node is designed, and a parallel processing method for NFV-enabled OTN nodes is proposed. To verify the performance of NFV-enabled SDON, the protocol interaction procedures of control function virtualization and node function virtualization are demonstrated on SDON testbed. Finally, the benefits and challenges of the parallel processing method for NFV-enabled OTN nodes are simulated and analyzed.
Virtual reality representations in contemporary media
Chan, Melanie
2014-01-01
The idea of virtual realities has a long and complex historical trajectory, spanning from Plato's concept of the cave and the simulacrum, to artistic styles such as Trompe L'oeil, and more recently developments in 3D film, television and gaming. However, this book will pay particular attention to the time between the 1980s to the 1990s when virtual reality and cyberspace were represented, particularly in fiction, as a wondrous technology that enabled transcendence from the limitations of physical embodiment. The purpose of this critical historical analysis of representations of virtual reality
Developing Mixed Reality Educational Applications: The Virtual Touch Toolkit
Directory of Open Access Journals (Sweden)
Juan Mateu
2015-08-01
Full Text Available In this paper, we present Virtual Touch, a toolkit that allows the development of educational activities through a mixed reality environment such that, using various tangible elements, the interconnection of a virtual world with the real world is enabled. The main goal of Virtual Touch is to facilitate the installation, configuration and programming of different types of technologies, abstracting the creator of educational applications from the technical details involving the use of tangible interfaces and virtual worlds. Therefore, it is specially designed to enable teachers to themselves create educational activities for their students in a simple way, taking into account that teachers generally lack advanced knowledge in computer programming and electronics. The toolkit has been used to develop various educational applications that have been tested in two secondary education high schools in Spain.
... this page: //medlineplus.gov/ency/article/003578.htm Toxicology screen To use the sharing features on this page, please enable JavaScript. A toxicology screen refers to various tests that determine the ...
Collaboration and dialogue in Virtual reality
DEFF Research Database (Denmark)
Gyldendahl Jensen, Camilla
2017-01-01
“Virtual reality” adds a new dimension to constructivist problem-based learning (PBL) environments in the architectural and building construction educations, where a realistic and lifelike presence in a building enables students to assess and discuss how the various solutions interact with each...... other. Combined with “Building Information Models” (BIM), “Virtual Reality” provides an entirely new opportunity to innovate and optimize the architecture and construction in its early stages, which creates and iterative learning process. There are several studies where virtual simulation tools based...... on predefined tutorials are tested for their ability to facilitate collaborative processes. This study addresses the problem from a new angle by the virtual universe created through the students' own iterative design of a building. The “Virtual reality” system's narrative tale arises spontaneously through...
Stereoselective virtual screening of the ZINC database using atom pair 3D-fingerprints.
Awale, Mahendra; Jin, Xian; Reymond, Jean-Louis
2015-01-01
Tools to explore large compound databases in search for analogs of query molecules provide a strategically important support in drug discovery to help identify available analogs of any given reference or hit compound by ligand based virtual screening (LBVS). We recently showed that large databases can be formatted for very fast searching with various 2D-fingerprints using the city-block distance as similarity measure, in particular a 2D-atom pair fingerprint (APfp) and the related category extended atom pair fingerprint (Xfp) which efficiently encode molecular shape and pharmacophores, but do not perceive stereochemistry. Here we investigated related 3D-atom pair fingerprints to enable rapid stereoselective searches in the ZINC database (23.2 million 3D structures). Molecular fingerprints counting atom pairs at increasing through-space distance intervals were designed using either all atoms (16-bit 3DAPfp) or different atom categories (80-bit 3DXfp). These 3D-fingerprints retrieved molecular shape and pharmacophore analogs (defined by OpenEye ROCS scoring functions) of 110,000 compounds from the Cambridge Structural Database with equal or better accuracy than the 2D-fingerprints APfp and Xfp, and showed comparable performance in recovering actives from decoys in the DUD database. LBVS by 3DXfp or 3DAPfp similarity was stereoselective and gave very different analogs when starting from different diastereomers of the same chiral drug. Results were also different from LBVS with the parent 2D-fingerprints Xfp or APfp. 3D- and 2D-fingerprints also gave very different results in LBVS of folded molecules where through-space distances between atom pairs are much shorter than topological distances. 3DAPfp and 3DXfp are suitable for stereoselective searches for shape and pharmacophore analogs of query molecules in large databases. Web-browsers for searching ZINC by 3DAPfp and 3DXfp similarity are accessible at www.gdb.unibe.ch and should provide useful assistance to drug
Virtual Reality for Materials Design Laboratory
Federal Laboratory Consortium — The purpose is to research and develop materials through applied virtual reality to enable interactive "materials-by-design." Extensive theoretical and computational...
GridSpace Engine of the ViroLab Virtual Laboratory
Ciepiela, E.; Kocot, J.; Gubala, T.; Malawski, M.; Kasztelnik, M.; Bubak, M.; Bubak, M.; Turała, M.; Wiatr, K.
2008-01-01
GridSpace Engine is the central operational unit of the ViroLab Virtual Laboratory. This specific runtime environment enables access to computational and data resources by coordinating execution of experiments written in the Ruby programming language extended with virtual laboratory capabilities.
Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0.
Koch, Mathilde; Duigou, Thomas; Carbonell, Pablo; Faulon, Jean-Loup
2017-12-19
Network generation tools coupled with chemical reaction rules have been mainly developed for synthesis planning and more recently for metabolic engineering. Using the same core algorithm, these tools apply a set of rules to a source set of compounds, stopping when a sink set of compounds has been produced. When using the appropriate sink, source and rules, this core algorithm can be used for a variety of applications beyond those it has been developed for. Here, we showcase the use of the open source workflow RetroPath2.0. First, we mathematically prove that we can generate all structural isomers of a molecule using a reduced set of reaction rules. We then use this enumeration strategy to screen the chemical space around a set of monomers and predict their glass transition temperatures, as well as around aminoglycosides to search structures maximizing antibacterial activity. We also perform a screening around aminoglycosides with enzymatic reaction rules to ensure biosynthetic accessibility. We finally use our workflow on an E. coli model to complete E. coli metabolome, with novel molecules generated using promiscuous enzymatic reaction rules. These novel molecules are searched on the MS spectra of an E. coli cell lysate interfacing our workflow with OpenMS through the KNIME Analytics Platform. We provide an easy to use and modify, modular, and open-source workflow. We demonstrate its versatility through a variety of use cases including molecular structure enumeration, virtual screening in the chemical space, and metabolome completion. Because it is open source and freely available on MyExperiment.org, workflow community contributions should likely expand further the features of the tool, even beyond the use cases presented in the paper.
Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z
2012-02-01
Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. Copyright © 2011 Elsevier Inc. All rights reserved.
A virtual reality test battery for assessment and screening of spatial neglect.
Fordell, H; Bodin, K; Bucht, G; Malm, J
2011-03-01
There is a need for improved screening methods for spatial neglect. To construct a VR-test battery and evaluate its accuracy and usability in patients with acute stroke. VR-DiSTRO consists of a standard desktop computer, a CRT monitor and eye shutter stereoscopic glasses, a force feedback interface, and software, developed to create an interactive and immersive 3D experience. VR-tests were developed and validated to the conventional Star Cancellation test, Line bisection, Baking Tray Task (BTT), and Visual Extinction test. A construct validation to The Rivermead Behavioral Inattention Test, used as criterion of visuospatial neglect, was made. Usability was assessed according to ISO 9241-11. Thirty-one patients with stroke were included, 9/31 patients had neglect. The sensitivity was 100% and the specificity 82% for the VR-DiSTRO to correctly identify neglect. VR-BTT and VR-Extinction had the highest correlation (r² = 0.64 and 0.78), as well as high sensitivity and specificity. The kappa values describing the agreement between traditional neglect tests and the corresponding virtual reality test were between 0.47-0.85. Usability was assessed by a questionnaire; 77% reported that the VR-DiSTRO was 'easy' to use. Eighty-eight percent reported that they felt 'focused', 'pleased' or 'alert'. No patient had adverse symptoms. The test session took 15 min. The VR-DiSTRO quickly and with a high accuracy identified visuospatial neglect in patients with stroke in this construct validation. The usability among elderly patients with stroke was high. This VR-test battery has the potential to become an important screening instrument for neglect and a valuable adjunct to the neuropsychological assessment. © 2010 John Wiley & Sons A/S.
Cloudified Mobility and Bandwidth Prediction in Virtualized LTE Networks
Zhao, Zongliang; Karimzadeh Motallebi Azar, Morteza; Braun, Torsten; Pras, Aiko; van den Berg, Hans Leo
Network Function Virtualization involves implementing network functions (e.g., virtualized LTE component) in software that can run on a range of industry standard server hardware, and can be migrated or instantiated on demand. A prediction service hosted on cloud infrastructures enables consumers to
Virtual Prototyping and Validation of Cpps within a New Software Framework
Directory of Open Access Journals (Sweden)
Sebastian Neumeyer
2017-02-01
Full Text Available As a result of the growing demand for highly customized and individual products, companies need to enable flexible and intelligent manufacturing. Cyber-physical production systems (CPPS will act autonomously in the future in an interlinked production and enable such flexibility. However, German mid-sized plant manufacturers rarely use virtual technologies for design and validation in order to design CPPS. The research project Virtual Commissioning with Smart Hybrid Prototyping (VIB-SHP investigated the usage of virtual technologies for manufacturing systems and CPPS design. Aspects of asynchronous communicating, intelligent- and autonomous-acting production equipment in an immersive validation environment, have been investigated. To enable manufacturing system designers to validate CPPS, a software framework for virtual prototyping has been developed. A mechatronic construction kit for production system design integrates discipline-specific models and manages them in a product lifecycle management (PLM solution. With this construction kit manufacturing designers are able to apply virtual technologies and the validation of communication processes with the help of behavior models. The presented approach resolves the sequential design process for the development of mechanical, electrical, and software elements and ensures the consistency of these models. With the help of a bill of material (BOM- and signal-based alignment of the discipline-specific models in an integrated mechatronic product model, the communication of the design status and changes are improved. The re-use of already-specified and -designed modules enable quick behavior modeling, code evaluation, as well as interaction with the virtualized assembly system in an immersive environment.
Software for virtual accelerator designing
International Nuclear Information System (INIS)
Kulabukhova, N.; Ivanov, A.; Korkhov, V.; Lazarev, A.
2012-01-01
The article discusses appropriate technologies for software implementation of the Virtual Accelerator. The Virtual Accelerator is considered as a set of services and tools enabling transparent execution of computational software for modeling beam dynamics in accelerators on distributed computing resources. Distributed storage and information processing facilities utilized by the Virtual Accelerator make use of the Service-Oriented Architecture (SOA) according to a cloud computing paradigm. Control system tool-kits (such as EPICS, TANGO), computing modules (including high-performance computing), realization of the GUI with existing frameworks and visualization of the data are discussed in the paper. The presented research consists of software analysis for realization of interaction between all levels of the Virtual Accelerator and some samples of middle-ware implementation. A set of the servers and clusters at St.-Petersburg State University form the infrastructure of the computing environment for Virtual Accelerator design. Usage of component-oriented technology for realization of Virtual Accelerator levels interaction is proposed. The article concludes with an overview and substantiation of a choice of technologies that will be used for design and implementation of the Virtual Accelerator. (authors)
Incorporating Virtually Immersive Environments as a Collaborative Medium for Virtual Teaming
Directory of Open Access Journals (Sweden)
Charles J. Lesko, Jr.
2012-08-01
Full Text Available Virtually immersive environments incorporate the use of various computer modelling and simulation techniques enabling geographically dispersed virtual project teams to interact within an artificially projected three-dimensional space online. This study focused on adoption of virtually immersive technologies as a collaborative media to support virtual teaming of both graduate and undergraduate-level project management students. The data and information from this study has implications for educators using virtually immersive environments in the classroom. In this study, we specifically evaluated two key components in this paper: 1 students’ level of trust and; 2 students’ willingness to use the technology, along with their belief about the virtual environment’s ability to extend and improve knowledge sharing in their team work environment. We learned that while students did find the environment a positive add on for working collaboratively, there were students who were neither more nor less likely to use the technology for future collaborative ventures. Most of the students who were not very positive about the environment were “fence sitters” likely indicating needs related to additional training to improve communication skills. Finally, based on the full study results we have provided basic recommendations designed to support team trust building in the system along with interpersonal trust building to facilitate knowledge transfer and better strategic us of the technology.
A novel anti-tumor inhibitor identified by virtual screen with PLK1 structure and zebrafish assay.
Directory of Open Access Journals (Sweden)
Jing Lu
Full Text Available Polo-like kinase 1 (PLK1, one of the key regulators of mitosis, is a target for cancer therapy due to its abnormally high activity in several tumors. Plk1 is highly conserved and shares a nearly identical 3-D structure between zebrafish and humans. The initial 10 mitoses of zebrafish embryonic cleavages occur every∼30 minutes, and therefore provide a rapid assay to evaluate mitosis inhibitors including those targeting Plk1. To increase efficiency and specificity, we first performed a computational virtual screen of∼60000 compounds against the human Plk1 3-D structure docked to both its kinase and Polo box domain. 370 candidates with the top free-energy scores were subjected to zebrafish assay and 3 were shown to inhibit cell division. Compared to general screen for compounds inhibiting zebrafish embryonic cleavage, computation increased the efficiency by 11 folds. One of the 3 compounds, named I2, was further demonstrated to effectively inhibit multiple tumor cell proliferation in vitro and PC3 prostate cancer growth in Xenograft mouse model in vivo. Furthermore, I2 inhibited Plk1 enzyme activity in a dose dependent manner. The IC50 values of I2 in these assays are compatible to those of ON-01910, a Plk1 inhibitor currently in Phase III clinic trials. Our studies demonstrate that zebrafish assays coupled with computational screening significantly improves the efficiency of identifying specific regulators of biological targets. The PLK1 inhibitor I2, and its analogs, may have potential in cancer therapeutics.
Poster: Virtual reality interaction using mobile devices
Aseeri, Sahar A.
2013-03-01
In this work we aim to implement and evaluate alternative approaches for interacting with virtual environments on mobile devices for navigation, object selection and manipulation. Interaction with objects in virtual worlds using traditional input such as current state-of-the-art devices is often difficult and could diminish the immersion and sense of presence when it comes to 3D virtual environment tasks. We have developed new methods to perform different kinds of interactions using a mobile device (e.g. a smartphone) both as input device, performing selection and manipulation of objects, and as output device, utilizing the screen as an extra view (virtual camera or information display). Our hypothesis is that interaction via mobile devices facilitates simple tasks like the ones described within immersive virtual reality systems. We present here our initial implementation and result. © 2013 IEEE.
Virtual Technologies and Social Shaping
Kreps , David
2010-01-01
International audience; Virtual Technologies have enabled us all to become publishers and broadcasters. The world of information has become saturated with a multitude of opinions, and opportunities to express them. Track 2 "Virtual Technologies and Social Shaping" of the 9th Conference on Human Choice and Computers (HCC9) explores some of the issues that have arisen in this new information society, how we are shaped by it, and how we shape it, through i) two papers addressing issues of identi...
Su, Chuan-Jun; Chiang, Chang-Yu; Chih, Meng-Chun
2014-03-07
Good physical fitness generally makes the body less prone to common diseases. A personalized exercise plan that promotes a balanced approach to fitness helps promotes fitness, while inappropriate forms of exercise can have adverse consequences for health. This paper aims to develop an ontology-driven knowledge-based system for generating custom-designed exercise plans based on a user's profile and health status, incorporating international standard Health Level Seven International (HL7) data on physical fitness and health screening. The generated plan exposing Representational State Transfer (REST) style web services which can be accessed from any Internet-enabled device and deployed in cloud computing environments. To ensure the practicality of the generated exercise plans, encapsulated knowledge used as a basis for inference in the system is acquired from domain experts. The proposed Ubiquitous Exercise Plan Generation for Personalized Physical Fitness (UFIT) will not only improve health-related fitness through generating personalized exercise plans, but also aid users in avoiding inappropriate work outs.
Su, Hao; Yan, Ji; Xu, Jian; Fan, Xi-Zhen; Sun, Xian-Lin; Chen, Kang-Yu
2015-08-01
Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling. The activation of RhoA/Rho-kinase (ROCK) pathway plays a central role in the pathologic progression of PH and thus the Rho kinase, an essential effector of the ROCK pathway, is considered as a potential therapeutic target to attenuate PH. In the current study, a synthetic pipeline is used to discover new potent Rho inhibitors from various natural products. In the pipeline, the stepwise high-throughput virtual screening, quantitative structure-activity relationship (QSAR)-based rescoring, and kinase assay were integrated. The screening was performed against a structurally diverse, drug-like natural product library, from which six identified compounds were tested to determine their inhibitory potencies agonist Rho by using a standard kinase assay protocol. With this scheme, we successfully identified two potent Rho inhibitors, namely phloretin and baicalein, with activity values of IC50 = 0.22 and 0.95 μM, respectively. Structural examination suggested that complicated networks of non-bonded interactions such as hydrogen bonding, hydrophobic forces, and van der Waals contacts across the complex interfaces of Rho kinase are formed with the screened compounds.
Virtual reality training improves balance function.
Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng
2014-09-01
Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function.
Virtual reality training improves balance function
Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng
2014-01-01
Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function. PMID:25368651
Manually locating physical and virtual reality objects.
Chen, Karen B; Kimmel, Ryan A; Bartholomew, Aaron; Ponto, Kevin; Gleicher, Michael L; Radwin, Robert G
2014-09-01
In this study, we compared how users locate physical and equivalent three-dimensional images of virtual objects in a cave automatic virtual environment (CAVE) using the hand to examine how human performance (accuracy, time, and approach) is affected by object size, location, and distance. Virtual reality (VR) offers the promise to flexibly simulate arbitrary environments for studying human performance. Previously, VR researchers primarily considered differences between virtual and physical distance estimation rather than reaching for close-up objects. Fourteen participants completed manual targeting tasks that involved reaching for corners on equivalent physical and virtual boxes of three different sizes. Predicted errors were calculated from a geometric model based on user interpupillary distance, eye location, distance from the eyes to the projector screen, and object. Users were 1.64 times less accurate (p virtual versus physical box corners using the hands. Predicted virtual targeting errors were on average 1.53 times (p virtual targets but not significantly different for close-up virtual targets. Target size, location, and distance, in addition to binocular disparity, affected virtual object targeting inaccuracy. Observed virtual box inaccuracy was less than predicted for farther locations, suggesting possible influence of cues other than binocular vision. Human physical interaction with objects in VR for simulation, training, and prototyping involving reaching and manually handling virtual objects in a CAVE are more accurate than predicted when locating farther objects.
Global tree network for computing structures enabling global processing operations
Blumrich; Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Hoenicke, Dirk; Steinmacher-Burow, Burkhard D.; Takken, Todd E.; Vranas, Pavlos M.
2010-01-19
A system and method for enabling high-speed, low-latency global tree network communications among processing nodes interconnected according to a tree network structure. The global tree network enables collective reduction operations to be performed during parallel algorithm operations executing in a computer structure having a plurality of the interconnected processing nodes. Router devices are included that interconnect the nodes of the tree via links to facilitate performance of low-latency global processing operations at nodes of the virtual tree and sub-tree structures. The global operations performed include one or more of: broadcast operations downstream from a root node to leaf nodes of a virtual tree, reduction operations upstream from leaf nodes to the root node in the virtual tree, and point-to-point message passing from any node to the root node. The global tree network is configurable to provide global barrier and interrupt functionality in asynchronous or synchronized manner, and, is physically and logically partitionable.
Hamrin, Per; Persson, Martin
2010-01-01
Virtual Teams are becoming an increasingly common work form. The ability to connect people with required sets of skills, regardless of their location in the world has been enabled by advances in information technology over the past 20 years. However, as researchers and practitioners have discovered, this new kind of team brings with it number of challenges. This thesis aims to examine the challenges and the opportunities that technology brings to the environment of the Virtual Team and to giv...
Integrated Data Visualization and Virtual Reality Tool
Dryer, David A.
1998-01-01
The Integrated Data Visualization and Virtual Reality Tool (IDVVRT) Phase II effort was for the design and development of an innovative Data Visualization Environment Tool (DVET) for NASA engineers and scientists, enabling them to visualize complex multidimensional and multivariate data in a virtual environment. The objectives of the project were to: (1) demonstrate the transfer and manipulation of standard engineering data in a virtual world; (2) demonstrate the effects of design and changes using finite element analysis tools; and (3) determine the training and engineering design and analysis effectiveness of the visualization system.
COLLABORATION AND DIALOGUE IN VIRTUAL REALITY
Camilla Gyldendahl Jensen
2017-01-01
“Virtual reality” adds a new dimension to constructivist problem-based learning (PBL) environments in the architectural and building construction educations, where a realistic and lifelike presence in a building enables students to assess and discuss how the various solutions interact with each other. Combined with “Building Information Models” (BIM), “Virtual Reality” provides an entirely new opportunity to innovate and optimize the architecture and construction in its early stages, which cr...
Invocation of Grid operations in the ViroLab Virtual Laboratory
Bartyński, T.; Malawski, M.; Bubak, M.; Bubak, M.; Turała, M.; Wiatr, K.
2008-01-01
This paper presents invocation of grid operations within the ViroLab Virtual Laboratory. Virtual laboratory enables users to develop and execute experiments that access computational resources on the Grid exposed via various middleware technologies. An abstraction over the Grid environment is
Mobile Screens: The Visual Regime of Navigation
Verhoeff, N.
2012-01-01
In this book on screen media, space, and mobility I compare synchronically, as well as diachronically, diverse and variegated screen media - their technologies and practices – as sites for virtual mobility and navigation. Mobility as a central trope can be found on the multiple levels that are
Yan, Guoyi; Hou, Manzhou; Luo, Jiang; Pu, Chunlan; Hou, Xueyan; Lan, Suke; Li, Rui
2018-02-01
Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.5 million compounds for BRD4 inhibitors using pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulations. As a result, two molecules of twelve hits were found to be active in bioactivity tests. Among the molecules, compound 5 exhibited potent anticancer activity, and the IC 50 values against human cancer cell lines MV4-11, A375, and HeLa were 4.2, 7.1, and 11.6 μm, respectively. After that, colony formation assay, cell cycle, apoptosis analysis, wound-healing migration assay, and Western blotting were carried out to learn the bioactivity of compound 5. © 2017 John Wiley & Sons A/S.
Virtualized endoscope system. An application of virtual reality technology to diagnostic aid
International Nuclear Information System (INIS)
Mori, Kensaku; Urano, Akihiro; Toriwaki, Jun-ichiro; Hasegawa, Jun-ichi; Anno, Hirofumi; Katada, Kazuhiro.
1996-01-01
In this paper we propose a new medical image processing system called 'Virtualized Endoscope System (VES)', which can examine the inside of a virtualized human body. The virtualized human body is a 3-D digital image which is taken by such as X-ray CT scanner or MRI scanner. VES consists of three modules; (1) imaging, (2) segmentation and reconstruction and (3) interactive operation. The interactive operation module has following three major functions; (a) display of, (b) measurement from, and (c) manipulation to the virtualized human body. The user of the system can observe freely both the inside and the outside of a target organ from any point and any direction freely, and can perform necessary measurement interactively concerning angle and length at any time during observation. VES enables to observe repeatedly an area where the real endoscope can not enter without pain from any direction which the real endoscope can not. We applied this system to real 3-D X-ray CT images and obtained good result. (author)
Virtual Reality as a Tool in the Education
Piovesan, Sandra Dutra; Passerino, Liliana Maria; Pereira, Adriana Soares
2012-01-01
The virtual reality is being more and more used in the education, enabling the student to find out, to explore and to build his own knowledge. This paper presents an Educational Software for presence or distance education, for subjects of Formal Language, where the student can manipulate virtually the target that must be explored, analyzed and…
Virtual Reality: A Strategy for Training in Cross-Cultural Communication.
Meyer, Catherine; Dunn-Roberts, Richard
1992-01-01
Defines virtual reality and explains terminology, theoretical concepts, and enabling technologies. Research and applications are described; limitations of current technology are considered; and future possibilities are discussed, including the use of virtual reality in training for cross-cultural communication. (22 references) (LRW)
Walking in Place Through Virtual Worlds
DEFF Research Database (Denmark)
Nilsson, Niels Chr.; Serafin, Stefania; Nordahl, Rolf
2016-01-01
Immersive virtual reality (IVR) is seemingly on the verge of entering the homes of consumers. Enabling users to walk through virtual worlds in a limited physical space presents a challenge. With an outset in a taxonomy of virtual travel techniques, we argue that Walking-in-Place (WIP) techniques...... constitute a promising approach to virtual walking in relation to consumer IVR. Subsequently we review existing approaches to WIP locomotion and highlight the need for a more explicit focus on the perceived naturalness of WIP techniques; i.e., the degree to which WIP locomotion feels like real walking....... Finally, we summarize work we have performed in order to produce more natural WIP locomotion and present unexplored topics which need to be address if WIP techniques are to provide perceptually natural walking experiences....
Hybrid rendering of the chest and virtual bronchoscopy [corrected].
Seemann, M D; Seemann, O; Luboldt, W; Gebicke, K; Prime, G; Claussen, C D
2000-10-30
Thin-section spiral computed tomography was used to acquire the volume data sets of the thorax. The tracheobronchial system and pathological changes of the chest were visualized using a color-coded surface rendering method. The structures of interest were then superimposed on a volume rendering of the other thoracic structures, thus producing a hybrid rendering. The hybrid rendering technique exploit the advantages of both rendering methods and enable virtual bronchoscopic examinations using different representation models. Virtual bronchoscopic examinations with a transparent color-coded shaded-surface model enables the simultaneous visualization of both the airways and the adjacent structures behind of the tracheobronchial wall and therefore, offers a practical alternative to fiberoptic bronchoscopy. Hybrid rendering and virtual endoscopy obviate the need for time consuming detailed analysis and presentation of axial source images.
Shattering the Screen: Embodied Narrative in Digital Media
Directory of Open Access Journals (Sweden)
Russell J. Cook
2017-03-01
Full Text Available This illustrated phenomenological inquiry into storytelling in screen media identifies important media transformations of experience. Viewers embody, or situate their experienced selves, according to screen requirements. A viewer’s compelled perspective on the screen causes fundamental spatio-temporal transformations of narrative experience, including horizontal stretching of screen space and time compression or leakage. Virtual media have the potential, as yet unrealized, to break out of the screen and to restore narrative to its primordial, experiential roots.
Virtualization of food supply chains with the internet of things
Verdouw, C.N.; Wolfert, J.; Beulens, A.J.M.; Rialland, A.
2016-01-01
Internet technologies allow supply chains to use virtualizations dynamically in operational management processes. This will improve support for food companies in dealing with perishable products, unpredictable supply variations and stringent food safety and sustainability requirements. Virtualization enables supply chain actors to monitor, control, plan and optimize business processes remotely and in real-time through the Internet, based on virtual objects instead of observation on-site. This...
The Role of Virtual Articulator in Prosthetic and Restorative Dentistry
Aljanakh, Mohammad
2014-01-01
Virtual reality is a computer based technology linked with the future of dentistry and dental practice. The virtual articulator is one such application in prosthetic and restorative dentistry based on virtual reality that will significantly reduce the limitations of the mechanical articulator, and by simulation of real patient data, allow analyses with regard to static and dynamic occlusion as well as to jaw relation. It is the purpose of this article to present the concepts and strategies for a future replacement of the mechanical articulator by a virtual one. Also, a brief note on virtual reality haptic system has been highlighted along with newly developed touch enabled virtual articulator. PMID:25177664
Virtual Networking Performance in OpenStack Platform for Network Function Virtualization
Directory of Open Access Journals (Sweden)
Franco Callegati
2016-01-01
Full Text Available The emerging Network Function Virtualization (NFV paradigm, coupled with the highly flexible and programmatic control of network devices offered by Software Defined Networking solutions, enables unprecedented levels of network virtualization that will definitely change the shape of future network architectures, where legacy telco central offices will be replaced by cloud data centers located at the edge. On the one hand, this software-centric evolution of telecommunications will allow network operators to take advantage of the increased flexibility and reduced deployment costs typical of cloud computing. On the other hand, it will pose a number of challenges in terms of virtual network performance and customer isolation. This paper intends to provide some insights on how an open-source cloud computing platform such as OpenStack implements multitenant network virtualization and how it can be used to deploy NFV, focusing in particular on packet forwarding performance issues. To this purpose, a set of experiments is presented that refer to a number of scenarios inspired by the cloud computing and NFV paradigms, considering both single tenant and multitenant scenarios. From the results of the evaluation it is possible to highlight potentials and limitations of running NFV on OpenStack.
Virtual commissioning of automated micro-optical assembly
Schlette, Christian; Losch, Daniel; Haag, Sebastian; Zontar, Daniel; Roßmann, Jürgen; Brecher, Christian
2015-02-01
In this contribution, we present a novel approach to enable virtual commissioning for process developers in micro-optical assembly. Our approach aims at supporting micro-optics experts to effectively develop assisted or fully automated assembly solutions without detailed prior experience in programming while at the same time enabling them to easily implement their own libraries of expert schemes and algorithms for handling optical components. Virtual commissioning is enabled by a 3D simulation and visualization system in which the functionalities and properties of automated systems are modeled, simulated and controlled based on multi-agent systems. For process development, our approach supports event-, state- and time-based visual programming techniques for the agents and allows for their kinematic motion simulation in combination with looped-in simulation results for the optical components. First results have been achieved for simply switching the agents to command the real hardware setup after successful process implementation and validation in the virtual environment. We evaluated and adapted our system to meet the requirements set by industrial partners-- laser manufacturers as well as hardware suppliers of assembly platforms. The concept is applied to the automated assembly of optical components for optically pumped semiconductor lasers and positioning of optical components for beam-shaping
An inductive database prototype based on virtual mining views
Blockeel, H.; Calders, T.; Fromont, É.; Goethals, B.; Prado, A.; Robardet, C.
2008-01-01
We present a prototype of an inductive database. Our system enables the user to query not only the data stored in the database but also generalizations (e.g. rules or trees) over these data through the use of virtual mining views. The mining views are relational tables that virtually contain the
Viscosity Measurement: A Virtual Experiment - Abstract of Issues 9907W
Papadopoulos, N.; Pitta, A. T.; Markopoulos, N.; Limniou, M.; Lemos, M. A. N. D. A.; Lemos, F.; Freire, F. G.
1999-11-01
Viscosity Measurement: A Virtual Experiment simulates a series of viscosity experiments. Viscosity is an important subject in chemistry and chemical engineering. It is important when dealing with intermolecular forces in liquids and gases and it has enormous relevance in all technological aspects of equipment dealing with liquids or gases. Most university-level chemistry courses include viscosity to some extent. Viscosity Measurement includes three virtual experiments: an Ostwald viscometer simulator, a falling-ball viscometer simulator, and a balance simulator for a simple determination of the density of a liquid. The Ostwald viscometer simulator and the balance simulator allow the student to find out how composition and temperature influence the density and viscosity of an ethanol-water mixture. The falling-ball viscometer simulator allows the student to determine experimentally the size and density of the ball required to measure viscosity of various liquids. Each virtual experiment includes a corresponding theoretical section. Support from the program is sufficient to enable the students to carry out a virtual experiment sensibly and on their own. Preparation is not essential. Students can use the program unsupervised, thus saving staff time and allowing flexibility in students' time. The design of the program interface plays a key role in the success of a simulated experiment. Direct manipulation has greater intuitive appeal than alternative interface forms such as menus and has been observed to provide performance and learning advantages (1). We tried to design an interface that is visually attractive, is user friendly with simple and intuitive navigation, and provides appropriate schematic animations to clarify the principles of the laboratory procedures. The opening screen presents the virtual experiments that can be selected. Clicking an icon takes the student to the appropriate section. Viscosity Measurement allows the student to concentrate on the
Directory of Open Access Journals (Sweden)
Malgorzata Szelag
Full Text Available Signal transducers and activators of transcription (STATs facilitate action of cytokines, growth factors and pathogens. STAT activation is mediated by a highly conserved SH2 domain, which interacts with phosphotyrosine motifs for specific STAT-receptor contacts and STAT dimerization. The active dimers induce gene transcription in the nucleus by binding to a specific DNA-response element in the promoter of target genes. Abnormal activation of STAT signaling pathways is implicated in many human diseases, like cancer, inflammation and auto-immunity. Searches for STAT-targeting compounds, exploring the phosphotyrosine (pTyr-SH2 interaction site, yielded many small molecules for STAT3 but sparsely for other STATs. However, many of these inhibitors seem not STAT3-specific, thereby questioning the present modeling and selection strategies of SH2 domain-based STAT inhibitors. We generated new 3D structure models for all human (hSTATs and developed a comparative in silico docking strategy to obtain further insight into STAT-SH2 cross-binding specificity of a selection of previously identified STAT3 inhibitors. Indeed, by primarily targeting the highly conserved pTyr-SH2 binding pocket the majority of these compounds exhibited similar binding affinity and tendency scores for all STATs. By comparative screening of a natural product library we provided initial proof for the possibility to identify STAT1 as well as STAT3-specific inhibitors, introducing the 'STAT-comparative binding affinity value' and 'ligand binding pose variation' as selection criteria. In silico screening of a multi-million clean leads (CL compound library for binding of all STATs, likewise identified potential specific inhibitors for STAT1 and STAT3 after docking validation. Based on comparative virtual screening and docking validation, we developed a novel STAT inhibitor screening tool that allows identification of specific STAT1 and STAT3 inhibitory compounds. This could increase our
Mobile viewer system for virtual 3D space using infrared LED point markers and camera
Sakamoto, Kunio; Taneji, Shoto
2006-09-01
The authors have developed a 3D workspace system using collaborative imaging devices. A stereoscopic display enables this system to project 3D information. In this paper, we describe the position detecting system for a see-through 3D viewer. A 3D display system is useful technology for virtual reality, mixed reality and augmented reality. We have researched spatial imaging and interaction system. We have ever proposed 3D displays using the slit as a parallax barrier, the lenticular screen and the holographic optical elements(HOEs) for displaying active image 1)2)3)4). The purpose of this paper is to propose the interactive system using these 3D imaging technologies. The observer can view virtual images in the real world when the user watches the screen of a see-through 3D viewer. The goal of our research is to build the display system as follows; when users see the real world through the mobile viewer, the display system gives users virtual 3D images, which is floating in the air, and the observers can touch these floating images and interact them such that kids can make play clay. The key technologies of this system are the position recognition system and the spatial imaging display. The 3D images are presented by the improved parallax barrier 3D display. Here the authors discuss the measuring method of the mobile viewer using infrared LED point markers and a camera in the 3D workspace (augmented reality world). The authors show the geometric analysis of the proposed measuring method, which is the simplest method using a single camera not the stereo camera, and the results of our viewer system.
Virtual reality boosts performance at AREVA Projects
International Nuclear Information System (INIS)
Bernasconi, F.
2017-01-01
AREVA Projects is one of the 6 business units of New AREVA and it is dedicated to engineering works in a vast fan of activities from mining to waste management via uranium chemistry and nuclear fuel recycling. AREVA projects has opted for innovation to improve performance. Since 2012 virtual reality has been used through the creation of a room equipped with a high-definition screen and stereoscopic goggles. At the beginning virtual reality was used to test and validate procedures for handling equipment thanks to a dynamical digital simulation of this equipment. Now virtual reality is massively used to validate the design phase of projects without having to fabricate a physical mock-up which saves time. The next step in the use of virtual reality is the implementation of a new version of devices like helmets, gloves... that will allow a better interaction with the virtual world. The continuously increasing of computer power is always pushing back the limits of what is possible in virtual reality. (A.C.)
Tripathi, Pranav; Chaudhary, Ritu; Singh, Ajeet
2014-01-01
Conventionally, drugs are discovered by testing chemically synthesized compounds against a battery of in vivo biological screens. Information technology and Omic science enabled us for high throughput screening of compound libraries against biological targets and hits are then tested for efficacy in cells or animals. Chancroid, caused by Haemophilus ducreyi is a public health problem and has been recognized as a cofactor for Human Immunodeficiency Virus (HIV) transmission. It facilitates HIV transmission by providing an accessible portal entry, promoting viral shedding, and recruiting macrophages as well as CD4 cells to the skin. So, there is a requirement to develop an efficient drug to combat Chancroid that can also diminish HIV infection. In-silico screening of potential inhibitors against the target may facilitate in detection of the novel lead compounds for developing an effective chemo preventive strategy against Haemophilus ducreyi. The present study has investigated the effects of approximately 1100 natural compounds that inhibit three vital enzymes viz. Phosphoenolpyruvate phosphotransferase, Acetyl-coenzyme A carboxylase and Fructose 1, 6-bisphosphatase of Haemophilus ducreyi in reference to a commercial drug Rifabutin. Results reveal that the lead compound uses less energy to bind to target. The lead compound parillin has also been predicted as less immunogenic in comparison to Rifabutin. Further, better molecular dynamics, pharmacokinetics, pharmacodynamics and ADME-T properties establish it as an efficient chancroid preventer.
[Virtual microscopy in pathology teaching and postgraduate training (continuing education)].
Sinn, H P; Andrulis, M; Mogler, C; Schirmacher, P
2008-11-01
As with conventional microscopy, virtual microscopy permits histological tissue sections to be viewed on a computer screen with a free choice of viewing areas and a wide range of magnifications. This, combined with the possibility of linking virtual microscopy to E-Learning courses, make virtual microscopy an ideal tool for teaching and postgraduate training in pathology. Uses of virtual microscopy in pathology teaching include blended learning with the presentation of digital teaching slides in the internet parallel to presentation in the histology lab, extending student access to histology slides beyond the lab. Other uses are student self-learning in the Internet, as well as the presentation of virtual slides in the classroom with or without replacing real microscopes. Successful integration of virtual microscopy depends on its embedding in the virtual classroom and the creation of interactive E-learning content. Applications derived from this include the use of virtual microscopy in video clips, podcasts, SCORM modules and the presentation of virtual microscopy using interactive whiteboards in the classroom.
NASA Virtual Institutes: International Bridges for Space Exploration
Schmidt, Gregory K.
2016-01-01
NASA created the first virtual institute, the NASA Astrobiology Institute (NAI), in 2009 with an aim toward bringing together geographically disparate and multidisciplinary teams toward the goal of answering broad questions in the then-new discipline of astrobiology. With the success of the virtual institute model, NASA then created the NASA Lunar Science Institute (NLSI) in 2008 to address questions of science and human exploration of the Moon, and then the NASA Aeronautics Research Institute (NARI) in 2012 which addresses key questions in the development of aeronautics technologies. With the broadening of NASA's human exploration targets to include Near Earth Asteroids and the moons of Mars as well as the Moon, the NLSI morphed into the Solar System Exploration Research Virtual Institute (SSERVI) in 2012. SSERVI funds domestic research teams to address broad questions at the intersection of science and human exploration, with the underlying principle that science enables human exploration, and human exploration enables science. Nine domestic teams were funded in 2014 for a five-year period to address a variety of different topics, and nine international partners (with more to come) also work with the U.S. teams on a variety of topics of mutual interest. The result is a robust and productive research infrastructure that is not only scientifically productive but can respond to strategic topics of domestic and international interest, and which develops a new generation of researchers. This is all accomplished with the aid of virtual collaboration technologies which enable scientific research at a distance. The virtual institute model is widely applicable to a range of space science and exploration problems.
Fernandez Montenegro, Juan Manuel; Argyriou, Vasileios
2017-05-01
Alzheimer's screening tests are commonly used by doctors to diagnose the patient's condition and stage as early as possible. Most of these tests are based on pen-paper interaction and do not embrace the advantages provided by new technologies. This paper proposes novel Alzheimer's screening tests based on virtual environments and game principles using new immersive technologies combined with advanced Human Computer Interaction (HCI) systems. These new tests are focused on the immersion of the patient in a virtual room, in order to mislead and deceive the patient's mind. In addition, we propose two novel variations of Turing Test proposed by Alan Turing as a method to detect dementia. As a result, four tests are introduced demonstrating the wide range of screening mechanisms that could be designed using virtual environments and game concepts. The proposed tests are focused on the evaluation of memory loss related to common objects, recent conversations and events; the diagnosis of problems in expressing and understanding language; the ability to recognize abnormalities; and to differentiate between virtual worlds and reality, or humans and machines. The proposed screening tests were evaluated and tested using both patients and healthy adults in a comparative study with state-of-the-art Alzheimer's screening tests. The results show the capacity of the new tests to distinguish healthy people from Alzheimer's patients. Copyright © 2017. Published by Elsevier Inc.
COLLABORATION AND DIALOGUE IN VIRTUAL REALITY
Directory of Open Access Journals (Sweden)
Camilla Gyldendahl Jensen
2017-01-01
Full Text Available “Virtual reality” adds a new dimension to constructivist problem-based learning (PBL environments in the architectural and building construction educations, where a realistic and lifelike presence in a building enables students to assess and discuss how the various solutions interact with each other. Combined with “Building Information Models” (BIM, “Virtual Reality” provides an entirely new opportunity to innovate and optimize the architecture and construction in its early stages, which creates and iterative learning process. There are several studies where virtual simulation tools based on predefined tutorials are tested for their ability to facilitate collaborative processes. This study addresses the problem from a new angle by the virtual universe created through the students' own iterative design of a building. The “Virtual reality” system's narrative tale arises spontaneously through the dialogue. The result of this study shows that “Virtual Reality”, as a tool, creates some changes in the dialogue conditions which affect the learning process. The use of “Virtual Reality” requires a very precise framing about the system's ability to facilitate a collaborative learning process. The analysis identifies several clear opportunities about incorporating gamification mechanisms known from e.g. video games software.
A manufactured past: virtual reality in archaeology
Directory of Open Access Journals (Sweden)
Glyn Goodrick
2004-01-01
Full Text Available Virtual reality and visualisation technologies developed over the past thirty years have been readily accessible to the archaeological community since the mid 1990s. Despite the high profile of virtual archaeology (Reilly 1991 both within the media and professional archaeology it has not been taken on board as a generally useful and standard technique by archaeologists. In this article we wish to discuss the technical and other issues which have resulted in a reluctance to adopt virtual archaeology and, more importantly, discuss ways forward that can enable us routinely to benefit from this technology in the diversity of archaeological practice.
Instructional Features for Training in Virtual Environments
National Research Council Canada - National Science Library
Singer, Michael J; Kring, Jason P; Hamilton, Roger M
2006-01-01
.... Virtual Environment (VE) technology, which typically includes head-mounted visual displays with tracking devices for limbs and individual weapons, provides increasing capabilities that enable a more immersed, person-centered...
Exploring Virtual Worlds With Head-Mounted Displays
Chung, James C.; Harris, Mark R.; Brooks, Frederick P.; Fuchs, Henry; Kelley, Michael T.; Hughes, John W.; Ouh-Young, Ming; Cheung, Clement; Holloway, Richard L.; Pique, Michael
1989-09-01
For nearly a decade the University of North Carolina at Chapel Hill has been conducting research in the use of simple head-mounted displays in "real-world" applications. Such units provide the user with non-holographic true three-dimensional information, since the kinetic depth effect, stereoscopy, and other visual cues combine to immerse the user in a "virtual world" which behaves like the real world in some respects. UNC's head-mounted display was built inexpensively from commercially available off-the-shelf components. Tracking of the the user's head position and orientation is performed by a Polhemus Navigation Sciences' 3SPACE* tracker. The host computer uses the tracking information to generate updated images corresponding to the user's new left eye and right eye views. The images are broadcast to two liquid crystal television screens (220x320 pixels) mounted on a horizontal shelf at the user's forehead. The user views these color screens through half-silvered mirrors, enabling the computer-generated image to be superimposed upon the user's real physical environment. The head-mounted display has been incorporated into existing molecular modeling and architectural applications being developed at UNC. In molecular structure studies, chemists are presented with a room-sized molecule with which they can interact in a manner more intuitive than that provided by conventional two-dimensional displays and dial boxes. Walking around and through the large molecule may provide quicker understanding of its structure, and such problems as drug-enzyme docking may be approached with greater insight. In architecture, the head-mounted display enables clients to better appreciate three-dimensional designs, which may be misinterpreted in their conventional two-dimensional form by untrained eyes. The addition of a treadmill to the system provides additional kinesthetic input into the understanding of building size and scale.
Virtual Interactive Space (VIS)
DEFF Research Database (Denmark)
Brooks, Anthony Lewis
2015-01-01
This paper shares code that enables the making of a Virtual Interactive Space (VIS) where the skin of the invisible active sensor area is dynamically responsive to the velocity of a limb e.g. hand. Used in proprioception training of movement the patch is at the core of the author’s Reafferentation...
2002-01-01
Ames Research Center granted Reality Capture Technologies (RCT), Inc., a license to further develop NASA's Mars Map software platform. The company incorporated NASA#s innovation into software that uses the Virtual Plant Model (VPM)(TM) to structure, modify, and implement the construction sites of industrial facilities, as well as develop, validate, and train operators on procedures. The VPM orchestrates the exchange of information between engineering, production, and business transaction systems. This enables users to simulate, control, and optimize work processes while increasing the reliability of critical business decisions. Engineers can complete the construction process and test various aspects of it in virtual reality before building the actual structure. With virtual access to and simulation of the construction site, project personnel can manage, access control, and respond to changes on complex constructions more effectively. Engineers can also create operating procedures, training, and documentation. Virtual Plant Model(TM) is a trademark of Reality Capture Technologies, Inc.
Virtual reality and planetary exploration
McGreevy, Michael W.
Exploring planetary environments is central to NASA's missions and goals. A new computing technology called Virtual Reality has much to offer in support of planetary exploration. This technology augments and extends human presence within computer-generated and remote spatial environments. Historically, NASA has been a leader in many of the fundamental concepts and technologies that comprise Virtual Reality. Indeed, Ames Research Center has a central role in the development of this rapidly emerging approach to using computers. This ground breaking work has inspired researchers in academia, industry, and the military. Further, NASA's leadership in this technology has spun off new businesses, has caught the attention of the international business community, and has generated several years of positive international media coverage. In the future, Virtual Reality technology will enable greatly improved human-machine interactions for more productive planetary surface exploration. Perhaps more importantly, Virtual Reality technology will democratize the experience of planetary exploration and thereby broaden understanding of, and support for, this historic enterprise.
Virtual reality and planetary exploration
Mcgreevy, Michael W.
1992-01-01
Exploring planetary environments is central to NASA's missions and goals. A new computing technology called Virtual Reality has much to offer in support of planetary exploration. This technology augments and extends human presence within computer-generated and remote spatial environments. Historically, NASA has been a leader in many of the fundamental concepts and technologies that comprise Virtual Reality. Indeed, Ames Research Center has a central role in the development of this rapidly emerging approach to using computers. This ground breaking work has inspired researchers in academia, industry, and the military. Further, NASA's leadership in this technology has spun off new businesses, has caught the attention of the international business community, and has generated several years of positive international media coverage. In the future, Virtual Reality technology will enable greatly improved human-machine interactions for more productive planetary surface exploration. Perhaps more importantly, Virtual Reality technology will democratize the experience of planetary exploration and thereby broaden understanding of, and support for, this historic enterprise.
Virtual reality and laparoscopic surgery.
Coleman, J; Nduka, C C; Darzi, A
1994-12-01
The nature of laparoscopic surgery makes it likely to benefit from current and future developments in virtual reality and telepresence technology. High-definition screens, three-dimensional sensory feedback and remote dextrous manipulation will be the next major developments in laparoscopic surgery. Simulators may be used in surgical training and in the evaluation of surgical capability.
Pathak, Rajesh Kumar; Baunthiyal, Mamta; Taj, Gohar; Kumar, Anil
2014-01-01
The HBx protein in Hepatitis B Virus (HBV) is a potential target for anti-liver cancer molecules. Therefore, it is of interest to screen known natural compounds against the HBx protein using molecular docking. However, the structure of HBx is not yet known. Therefore, the predicted structure of HBx using threading in LOMET was used for docking against plant derived natural compounds (curcumin, oleanolic acid, resveratrol, bilobetin, luteoline, ellagic acid, betulinic acid and rutin) by Molegro Virtual Docker. The screening identified rutin with binding energy of -161.65 Kcal/mol. Thus, twenty derivatives of rutin were further designed and screened against HBx. These in silico experiments identified compounds rutin01 (-163.16 Kcal/mol) and rutin08 (- 165.76 Kcal/mol) for further consideration and downstream validation. PMID:25187683
Enabling immersive simulation.
Energy Technology Data Exchange (ETDEWEB)
McCoy, Josh (University of California Santa Cruz, Santa Cruz, CA); Mateas, Michael (University of California Santa Cruz, Santa Cruz, CA); Hart, Derek H.; Whetzel, Jonathan; Basilico, Justin Derrick; Glickman, Matthew R.; Abbott, Robert G.
2009-02-01
The object of the 'Enabling Immersive Simulation for Complex Systems Analysis and Training' LDRD has been to research, design, and engineer a capability to develop simulations which (1) provide a rich, immersive interface for participation by real humans (exploiting existing high-performance game-engine technology wherever possible), and (2) can leverage Sandia's substantial investment in high-fidelity physical and cognitive models implemented in the Umbra simulation framework. We report here on these efforts. First, we describe the integration of Sandia's Umbra modular simulation framework with the open-source Delta3D game engine. Next, we report on Umbra's integration with Sandia's Cognitive Foundry, specifically to provide for learning behaviors for 'virtual teammates' directly from observed human behavior. Finally, we describe the integration of Delta3D with the ABL behavior engine, and report on research into establishing the theoretical framework that will be required to make use of tools like ABL to scale up to increasingly rich and realistic virtual characters.
Sounds of silence: How to animate virtual worlds with sound
Astheimer, Peter
1993-01-01
Sounds are an integral and sometimes annoying part of our daily life. Virtual worlds which imitate natural environments gain a lot of authenticity from fast, high quality visualization combined with sound effects. Sounds help to increase the degree of immersion for human dwellers in imaginary worlds significantly. The virtual reality toolkit of IGD (Institute for Computer Graphics) features a broad range of standard visual and advanced real-time audio components which interpret an object-oriented definition of the scene. The virtual reality system 'Virtual Design' realized with the toolkit enables the designer of virtual worlds to create a true audiovisual environment. Several examples on video demonstrate the usage of the audio features in Virtual Design.
Managing Virtual Product Development team: A Review
Directory of Open Access Journals (Sweden)
Amir Mohammad Colabi
2014-05-01
Full Text Available Although there are many potential benefits associated with the use of virtual product development teams, exploiting these benefits requires an appropriate management. Managing virtual product development team is a critical issue as many of these teams fail to accomplish their goals. Review of previous literature shows that body of knowledge in managing virtual product development teams is fragmented and inconsistent. The main objective of this paper is to categorize the previous research on the subject of virtual product development team management in order to integrate the research into a thematic model and to enable recommendations for future research. So, this study reviews and summarizes empirical research in the field, also conceptual and qualitative papers, experiences, reports and explorative case studies. Results show that there are three fields of research in this area, including: Virtual production and Virtual team in Product Development, Managing virtual team in R&D[1] and product development, Managing global virtual product development teams. In order to organize previous studies in this area, a thematic map is proposed which shows the structure and sequence of research. Finally, a comprehensive discussion on the future directions in this field is proposed.
Brovelli, M.; Hogan, P.; Minghini, M.; Zamboni, G.
2013-10-01
Inspired by the visionary idea of Digital Earth, as well as from the tremendous improvements in geo-technologies, use of virtual globes has been changing the way people approach to geographic information on the Web. Unlike the traditional 2D-visualization typical of Geographic Information Systems (GIS), virtual globes offer multi-dimensional, fully-realistic content visualization which allows for a much richer user experience. This research investigates the potential for using virtual globes to foster tourism and enhance cultural heritage. The paper first outlines the state of the art for existing virtual globes, pointing out some possible categorizations according to license type, platform-dependence, application type, default layers, functionalities and freedom of customization. Based on this analysis, the NASA World Wind virtual globe is the preferred tool for promoting tourism and cultural heritage. This is because its open source nature allows unlimited customization (in terms of both data and functionalities), and its Java core supports platform-independence. Relevant tourism-oriented World Wind-based applications, dealing with both the Web promotion of historical cartography and the setup of a participatory Web platform exploiting crowd-sourced data, are described. Finally, the paper presents a project focusing on the promotion of the Via Regina area (crossing the border between Italy and Switzerland) through an ad hoc World Wind customization. World Wind can thus be considered an ideal virtual globe for tourism applications, as it can be shaped to increase awareness of cultural history and, in turn, enhance touristic experience.
Enabler for the agile virtual enterprise
Fuerst, Karl; Schmidt, Thomas; Wippel, Gerald
2001-10-01
In this presentation, a new approach for a flexible low-cost Internet extended enterprise (project FLoCI-EE) will be presented. FLoCI-EE is a project in the fifth framework program of the European commission with 8 partners from 4 countries, which started in January 2001 and will be finished in December 2003. The main objective of FLoCI-EE is the development of a software prototype, which enables flexible enterprise cooperation with the aim to design, manufacture and sell products commonly, independent of enterprise borderlines. The needed IT-support includes functions of product data management (PDM), enterprise resource planning (ERP), supply chain management (SCM) and customer relationship management (CRM). Especially for small and medium sized enterprises, existing solutions are too expensive and inflexible to be of use under current turbulent market conditions. The second part of this paper covers the item Web Services, because in the role-specific support approach of FLoCI-EE, there are user- interface-components, which are tailored for specific roles in an enterprise. These components integrate automatically the services of the so-called basic-components, and the externally offered Web Services like UDDI.
The role of presence in virtual reality exposure therapy
Price, Matthew; Anderson, Page
2006-01-01
A growing body of literature suggests that virtual reality is a successful tool for exposure therapy in the treatment of anxiety disorders. Virtual reality (VR) researchers posit the construct of presence, defined as the interpretation of an artificial stimulus as if it were real, to be a presumed factor that enables anxiety to be felt during virtual reality exposure therapy (VRE). However, a handful of empirical studies on the relation between presence and anxiety in VRE have yielded mixed f...
Virtual Mirror gaming in libraries
Speelman, M.; Kröse, B.; Nijholt, A.; Poppe, R.
2008-01-01
This paper presents a study on a natural interface game in the context of a library. We developed a camera-based Virtual Mirror (VM) game, in which the player can see himself on the screen as if he looks at a mirror image. We present an overview of the different aspects of VM games and technologies
McGuire, Ross; Verhoeven, Stefan; Vass, Márton; Vriend, Gerrit; de Esch, Iwan J P; Lusher, Scott J; Leurs, Rob; Ridder, Lars; Kooistra, Albert J; Ritschel, Tina; de Graaf, Chris
2017-02-27
3D-e-Chem-VM is an open source, freely available Virtual Machine ( http://3d-e-chem.github.io/3D-e-Chem-VM/ ) that integrates cheminformatics and bioinformatics tools for the analysis of protein-ligand interaction data. 3D-e-Chem-VM consists of software libraries, and database and workflow tools that can analyze and combine small molecule and protein structural information in a graphical programming environment. New chemical and biological data analytics tools and workflows have been developed for the efficient exploitation of structural and pharmacological protein-ligand interaction data from proteomewide databases (e.g., ChEMBLdb and PDB), as well as customized information systems focused on, e.g., G protein-coupled receptors (GPCRdb) and protein kinases (KLIFS). The integrated structural cheminformatics research infrastructure compiled in the 3D-e-Chem-VM enables the design of new approaches in virtual ligand screening (Chemdb4VS), ligand-based metabolism prediction (SyGMa), and structure-based protein binding site comparison and bioisosteric replacement for ligand design (KRIPOdb).
Khovanov homology for virtual knots with arbitrary coefficients
International Nuclear Information System (INIS)
Manturov, Vassily O
2007-01-01
The Khovanov homology theory over an arbitrary coefficient ring is extended to the case of virtual knots. We introduce a complex which is well-defined in the virtual case and is homotopy equivalent to the original Khovanov complex in the classical case. Unlike Khovanov's original construction, our definition of the complex does not use any additional prescription of signs to the edges of a cube. Moreover, our method enables us to construct a Khovanov homology theory for 'twisted virtual knots' in the sense of Bourgoin and Viro (including knots in three-dimensional projective space). We generalize a number of results of Khovanov homology theory (the Wehrli complex, minimality problems, Frobenius extensions) to virtual knots with non-orientable atoms
Grid Enabled Geospatial Catalogue Web Service
Chen, Ai-Jun; Di, Li-Ping; Wei, Ya-Xing; Liu, Yang; Bui, Yu-Qi; Hu, Chau-Min; Mehrotra, Piyush
2004-01-01
Geospatial Catalogue Web Service is a vital service for sharing and interoperating volumes of distributed heterogeneous geospatial resources, such as data, services, applications, and their replicas over the web. Based on the Grid technology and the Open Geospatial Consortium (0GC) s Catalogue Service - Web Information Model, this paper proposes a new information model for Geospatial Catalogue Web Service, named as GCWS which can securely provides Grid-based publishing, managing and querying geospatial data and services, and the transparent access to the replica data and related services under the Grid environment. This information model integrates the information model of the Grid Replica Location Service (RLS)/Monitoring & Discovery Service (MDS) with the information model of OGC Catalogue Service (CSW), and refers to the geospatial data metadata standards from IS0 19115, FGDC and NASA EOS Core System and service metadata standards from IS0 191 19 to extend itself for expressing geospatial resources. Using GCWS, any valid geospatial user, who belongs to an authorized Virtual Organization (VO), can securely publish and manage geospatial resources, especially query on-demand data in the virtual community and get back it through the data-related services which provide functions such as subsetting, reformatting, reprojection etc. This work facilitates the geospatial resources sharing and interoperating under the Grid environment, and implements geospatial resources Grid enabled and Grid technologies geospatial enabled. It 2!so makes researcher to focus on science, 2nd not cn issues with computing ability, data locztic, processir,g and management. GCWS also is a key component for workflow-based virtual geospatial data producing.
A virtual radiation therapy workflow training simulation
International Nuclear Information System (INIS)
Bridge, P.; Crowe, S.B.; Gibson, G.; Ellemor, N.J.; Hargrave, C.; Carmichael, M.
2016-01-01
Aim: Simulation forms an increasingly vital component of clinical skills development in a wide range of professional disciplines. Simulation of clinical techniques and equipment is designed to better prepare students for placement by providing an opportunity to learn technical skills in a “safe” academic environment. In radiotherapy training over the last decade or so this has predominantly comprised treatment planning software and small ancillary equipment such as mould room apparatus. Recent virtual reality developments have dramatically changed this approach. Innovative new simulation applications and file processing and interrogation software have helped to fill in the gaps to provide a streamlined virtual workflow solution. This paper outlines the innovations that have enabled this, along with an evaluation of the impact on students and educators. Method: Virtual reality software and workflow applications have been developed to enable the following steps of radiation therapy to be simulated in an academic environment: CT scanning using a 3D virtual CT scanner simulation; batch CT duplication; treatment planning; 3D plan evaluation using a virtual linear accelerator; quantitative plan assessment, patient setup with lasers; and image guided radiotherapy software. Results: Evaluation of the impact of the virtual reality workflow system highlighted substantial time saving for academic staff as well as positive feedback from students relating to preparation for clinical placements. Students valued practice in the “safe” environment and the opportunity to understand the clinical workflow ahead of clinical department experience. Conclusion: Simulation of most of the radiation therapy workflow and tasks is feasible using a raft of virtual reality simulation applications and supporting software. Benefits of this approach include time-saving, embedding of a case-study based approach, increased student confidence, and optimal use of the clinical environment
Virtual Surgery in Congenital Heart Disease
DEFF Research Database (Denmark)
Sørensen, Thomas Sangild; Mosegaard, Jesper; Kislinskiy, Stefan
2014-01-01
et al., Cardiol Young 13:451–460, 2003). In combination with the availability of virtual models of congenital heart disease (CHD), techniques for computer- based simulation of cardiac interventions have enabled early clinical exploration of the emerging concept of virtual surgery (Sorensen et al...... Teaching, diagnosing, and planning of therapy in patients with complex structural cardiovascular heart disease require profound understanding of the three-dimensional (3D) nature of cardiovascular structures in these patients. To obtain such understanding, modern imaging modalities provide high...
A Systematic, Inquiry-Based 7-Step Virtual Worlds Teacher Training
Nussli, Natalie Christina; Oh, Kevin
2015-01-01
Eighteen special education teachers explored one prominent example of three-dimensional virtual worlds, namely Second Life. This study aimed to (a) determine their perception of the effectiveness of a systematic 7-Step Virtual Worlds Teacher Training workshop in terms of enabling them to make informed decisions about the usability of virtual…
The jabber chat tool EFDA Messenger and screen sharing tool EFDATV
Energy Technology Data Exchange (ETDEWEB)
Thomsen, K. [EFDA Close Support Unit Garching, Boltzmannstr. 2, D-85748 Garching (Germany)], E-mail: Knud.Thomsen@efda.org; Beck, S. [EFDA Close Support Unit Garching, Boltzmannstr. 2, D-85748 Garching (Germany); Wilhelm, B. [EFDA CSU Barcelona, c/Josep Pla n.2, Torres Diag. Litoral Edificio B3, 7a planta, 08019 Barcelona (Spain)
2008-04-15
Two Remote Participation (RP) tools are described. The first tool, named EFDA Messenger, is a secure Instant Messaging (IM) tool based on a Jabber server that only accepts SSL encrypted communication and does not allow file transfers as well as audio and video transmissions. This tool is useful to have as another mean of communication during video or teleconferences. The second tool, named EFDATV, is a multipurposeVirtual Network Computing (VNC) based desktop screen sharing system used to share presentations via the Internet. A Java enabled web browser or a VNC client is sufficient for the presenter and the audience to use EFDATV. It is also possible from an EFDATV channel to connect to another VNC server and broadcast the view from that VNC server.
The jabber chat tool EFDA Messenger and screen sharing tool EFDATV
International Nuclear Information System (INIS)
Thomsen, K.; Beck, S.; Wilhelm, B.
2008-01-01
Two Remote Participation (RP) tools are described. The first tool, named EFDA Messenger, is a secure Instant Messaging (IM) tool based on a Jabber server that only accepts SSL encrypted communication and does not allow file transfers as well as audio and video transmissions. This tool is useful to have as another mean of communication during video or teleconferences. The second tool, named EFDATV, is a multipurposeVirtual Network Computing (VNC) based desktop screen sharing system used to share presentations via the Internet. A Java enabled web browser or a VNC client is sufficient for the presenter and the audience to use EFDATV. It is also possible from an EFDATV channel to connect to another VNC server and broadcast the view from that VNC server
Virtual Reality: Is It Real Or Not?
Directory of Open Access Journals (Sweden)
S. Serap Kurbanoğlu
1996-01-01
Full Text Available In this paper virtual reality technology and how libraries might be affected by this technology are examined. Virtual reality sets out to address a problem. The problem is that of user-friendliness of computer systems. Needless to say, the current generation of computers still involves a barrier between human and machine. This is keyboard or mouse on the human side, and the screen on the computer side. If computers are really going to become a part of everyone’s normal day to day experiences, they, must allow users to visualise information in a way familiar to them, not the way the computers forces them to. Virtual reality provides such a way. With the increasing amounts of information available in electronic form, it is clear that virtual reality technology will have a profound impact on libraries.
Duffy, Fergal J; O'Donovan, Darragh; Devocelle, Marc; Moran, Niamh; O'Connell, David J; Shields, Denis C
2015-03-23
Protein-protein and protein-peptide interactions are responsible for the vast majority of biological functions in vivo, but targeting these interactions with small molecules has historically been difficult. What is required are efficient combined computational and experimental screening methods to choose among a number of potential protein interfaces worthy of targeting lead macrocyclic compounds for further investigation. To achieve this, we have generated combinatorial 3D virtual libraries of short disulfide-bonded peptides and compared them to pharmacophore models of important protein-protein and protein-peptide structures, including short linear motifs (SLiMs), protein-binding peptides, and turn structures at protein-protein interfaces, built from 3D models available in the Protein Data Bank. We prepared a total of 372 reference pharmacophores, which were matched against 108,659 multiconformer cyclic peptides. After normalization to exclude nonspecific cyclic peptides, the top hits notably are enriched for mimetics of turn structures, including a turn at the interaction surface of human α thrombin, and also feature several protein-binding peptides. The top cyclic peptide hits also cover the critical "hot spot" interaction sites predicted from the interaction crystal structure. We have validated our method by testing cyclic peptides predicted to inhibit thrombin, a key protein in the blood coagulation pathway of important therapeutic interest, identifying a cyclic peptide inhibitor with lead-like activity. We conclude that protein interfaces most readily targetable by cyclic peptides and related macrocyclic drugs may be identified computationally among a set of candidate interfaces, accelerating the choice of interfaces against which lead compounds may be screened.
The Virtual and the Real in Planning and Urban Design: Perspectives, Practices and Applications
Yamu, Claudia; Poplin, Alenka; Devisch, Oswald; de Roo, Gert
2018-01-01
The Virtual and the Real: Perspectives, Practices and Applications for the Built Environment explores the merging relationship between physical and virtual spaces in planning and urban design. Technological advances such as smart sensors, interactive screens, locative media and evolving computation
Spyrakis, Francesca; Cavasotto, Claudio N
2015-10-01
Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical "structural" issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns. Copyright © 2015 Elsevier Inc. All rights reserved.
Glenn Reconfigurable User-interface and Virtual reality Exploration (GURVE) Laboratory
Federal Laboratory Consortium — The GRUVE (Glenn Reconfigurable User-interface and Virtual reality Exploration) Lab is a reconfigurable, large screen display facility at Nasa Glenn Research Center....
Modeling of luminance distribution in CAVE-type virtual reality systems
Meironke, Michał; Mazikowski, Adam
2017-08-01
At present, one of the most advanced virtual reality systems are CAVE-type (Cave Automatic Virtual Environment) installations. Such systems are usually consisted of four, five or six projection screens and in case of six screens arranged in form of a cube. Providing the user with a high level of immersion feeling in such systems is largely dependent of optical properties of the system. The modeling of physical phenomena plays nowadays a huge role in the most fields of science and technology. It allows to simulate work of device without a need to make any changes in the physical constructions. In this paper distribution of luminance in CAVE-type virtual reality systems were modelled. Calculations were performed for the model of 6-walled CAVE-type installation, based on Immersive 3D Visualization Laboratory, situated at the Faculty of Electronics, Telecommunications and Informatics at the Gdańsk University of Technology. Tests have been carried out for two different scattering distribution of the screen material in order to check how these characteristicinfluence on the luminance distribution of the whole CAVE. The basis assumption and simplification of modeled CAVE-type installation and results were presented. The brief discussion about the results and usefulness of developed model were also carried out.
Framework for virtual control desk projects
Energy Technology Data Exchange (ETDEWEB)
Mol, Antonio Carlos A.; Freitas, Victor Goncalves G.; Espieito Santos, Andre Cotelli do; Aghina, Mauricio A. da C. e, E-mail: mol@ien.gov.b, E-mail: vgoncalves@ien.gov.b, E-mail: mag@ien.gov.b [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)
2011-07-01
Through the recent advances of the Brazilian nuclear program, the creation of virtual control desks allows an ergonomic evaluation and technique of the same, even before its physical implementation, reducing costs and time in addition to allow the virtual training of operators. This project intends to develop a 'framework' where the components of a real control desk are available for creating a virtual desk, continuing the project control desk developed at the Laboratorio de Interface Homem Sistema do IEN (LABHIS/IEN). Through the C++ programming language integrated with the OPENGL graphics library was possible to create the desk and it's components, allowing a graphical modeling in 3D (stereo) of a virtual control desk where the operator, with the aid of GLUI user interface library, can choose what and where the components are positioned on the bench, and select the type of desk wanted from the pre-defined templates. Finally, with the control desk mounted and configured, enabling a virtual interaction with operators, making possible to reproduce its functionalities. (author)
Framework for virtual control desk projects
International Nuclear Information System (INIS)
Mol, Antonio Carlos A.; Freitas, Victor Goncalves G.; Espieito Santos, Andre Cotelli do; Aghina, Mauricio A. da C. e
2011-01-01
Through the recent advances of the Brazilian nuclear program, the creation of virtual control desks allows an ergonomic evaluation and technique of the same, even before its physical implementation, reducing costs and time in addition to allow the virtual training of operators. This project intends to develop a 'framework' where the components of a real control desk are available for creating a virtual desk, continuing the project control desk developed at the Laboratorio de Interface Homem Sistema do IEN (LABHIS/IEN). Through the C++ programming language integrated with the OPENGL graphics library was possible to create the desk and it's components, allowing a graphical modeling in 3D (stereo) of a virtual control desk where the operator, with the aid of GLUI user interface library, can choose what and where the components are positioned on the bench, and select the type of desk wanted from the pre-defined templates. Finally, with the control desk mounted and configured, enabling a virtual interaction with operators, making possible to reproduce its functionalities. (author)
Exploring 4D Flow Data in an Immersive Virtual Environment
Stevens, A. H.; Butkiewicz, T.
2017-12-01
Ocean models help us to understand and predict a wide range of intricate physical processes which comprise the atmospheric and oceanic systems of the Earth. Because these models output an abundance of complex time-varying three-dimensional (i.e., 4D) data, effectively conveying the myriad information from a given model poses a significant visualization challenge. The majority of the research effort into this problem has concentrated around synthesizing and examining methods for representing the data itself; by comparison, relatively few studies have looked into the potential merits of various viewing conditions and virtual environments. We seek to improve our understanding of the benefits offered by current consumer-grade virtual reality (VR) systems through an immersive, interactive 4D flow visualization system. Our dataset is a Regional Ocean Modeling System (ROMS) model representing a 12-hour tidal cycle of the currents within New Hampshire's Great Bay estuary. The model data was loaded into a custom VR particle system application using the OpenVR software library and the HTC Vive hardware, which tracks a headset and two six-degree-of-freedom (6DOF) controllers within a 5m-by-5m area. The resulting visualization system allows the user to coexist in the same virtual space as the data, enabling rapid and intuitive analysis of the flow model through natural interactions with the dataset and within the virtual environment. Whereas a traditional computer screen typically requires the user to reposition a virtual camera in the scene to obtain the desired view of the data, in virtual reality the user can simply move their head to the desired viewpoint, completely eliminating the mental context switches from data exploration/analysis to view adjustment and back. The tracked controllers become tools to quickly manipulate (reposition, reorient, and rescale) the dataset and to interrogate it by, e.g., releasing dye particles into the flow field, probing scalar velocities
Maia, Eduardo Habib Bechelane; Campos, Vinícius Alves; Dos Reis Santos, Bianca; Costa, Marina Santos; Lima, Iann Gabriel; Greco, Sandro J; Ribeiro, Rosy I M A; Munayer, Felipe M; da Silva, Alisson Marques; Taranto, Alex Gutterres
2017-01-01
Octopus is an automated workflow management tool that is scalable for virtual high-throughput screening (vHTS). It integrates MOPAC2016, MGLTools, PyMOL, and AutoDock Vina. In contrast to other platforms, Octopus can perform docking simulations of an unlimited number of compounds into a set of molecular targets. After generating the ligands in a drawing package in the Protein Data Bank (PDB) format, Octopus can carry out geometry refinement using the semi-empirical method PM7 implemented in MOPAC2016. Docking simulations can be performed using AutoDock Vina and can utilize the Our Own Molecular Targets (OOMT) databank. Finally, the proposed software compiles the best binding energies into a standard table. Here, we describe two successful case studies that were verified by biological assay. In the first case study, the vHTS process was carried out for 22 (phenylamino)urea derivatives. The vHTS process identified a metalloprotease with the PDB code 1GKC as a molecular target for derivative LE&007. In a biological assay, compound LE&007 was found to inhibit 80% of the activity of this enzyme. In the second case study, compound Tx001 was submitted to the Octopus routine, and the results suggested that Plasmodium falciparum ATP6 (PfATP6) as a molecular target for this compound. Following an antimalarial assay, Tx001 was found to have an inhibitory concentration (IC 50 ) of 8.2 μM against PfATP6. These successful examples illustrate the utility of this software for finding appropriate molecular targets for compounds. Hits can then be identified and optimized as new antineoplastic and antimalarial drugs. Finally, Octopus has a friendly Linux-based user interface, and is available at www.drugdiscovery.com.br . Graphical Abstract Octopus: A platform for inverse virtual screening (IVS) to search new molecular targets for drugs.
Uniqueness of Experience and Virtual Playworlds: Playing Is Not Just for Fun
Talamo, Alessandra; Pozzi, Simone; Mellini, Barbara
2010-01-01
Social interactions within virtual communities are often described solely as being online experiences. Such descriptions are limited, for they fail to reference life external to the screen. The terms "virtual" and "real" have a negative connotation for many people and can even be interpreted to mean that something is "false" or "inauthentic."…
Alvarez-Ginarte, Yoanna María; Montero-Cabrera, Luis Alberto; García-de la Vega, José Manuel; Bencomo-Martínez, Alberto; Pupo, Amaury; Agramonte-Delgado, Alina; Marrero-Ponce, Yovani; Ruiz-García, José Alberto; Mikosch, Hans
2013-11-01
Parallel ligand- and structure-based virtual screenings of 269 steroids with anabolic activity evaluated in vivo were performed. The quantitative structure-activity relationship (QSAR) model expressed by selected descriptors as the octanol-water partition coefficient, the molar volume and the quantum mechanical calculated charge values on atoms C1, C2, C5, C9, C10, C14 and C17 of the steroid skeleton, expresses structural features of anabolic steroids (AS) contributing to the transport and steroid-receptor interaction. On the other hand, computational simulations of a candidate ligand binding to a receptor study (a "docking" procedure) predict the association of these AS with the human androgen receptor (AR). Fourteen compounds were identified as lead; the most potent was the 7α-methylestr-4-en-3, 17-dione. It was concluded that a good anabolic activity requires hydrogen bonding interactions between both Arg752 and Gln711 residues in the cycles A with O3 atom of the steroid and either Asn705 and Thr877 residues in the cycles D of steroid with O17 atom. Copyright © 2013 Elsevier Ltd. All rights reserved.
Virtualization of System of Systems Test and Evaluation
2012-06-04
computers and is the primary enabler for virtualization. 2. Virtualization System Elements Parmalee, Peterson , Tillman, & Hatfield (1972) outlined the...The work of Abu-Taieh and El Sheikh, based on the work of Balci (1994, 1995), and Balci et al. ( 1996 ), seeks to organize types of tests and to...and testing. In A. Dasso & A. Funes (Eds.), Verification, validation, and testing in software engineering (pp. 155–184). Hershey , PA: Idea Group
Virtual materiality, potentiality and subjctivity
DEFF Research Database (Denmark)
Søndergaard, Dorte Marie
2013-01-01
, of movies and of dreams as they enter intra-activities in the comprehensive set of apparatuses that enact child agency, subjectivity and relational practices. The analyses and conceptual refinements are based on empirical cases involving interviews with and observations among 8-14 year old children.......How do we conceptualize virtual materiality, in terms of for instance avatars and weapons in computer games, virtual discourse and subjectivity as phenomena intra-acting with real life materiality, discourse and subjectivity in children’s everyday lives? How do we understand the intra......-activity of such elements in children’s night dreams? These are some of the questions discussed in this text. I bring together Karen Barad’s agential realism and Giorgi Agamben’s concept of potentiality to enable and refine an analytical approach to real-virtual enactments, thereby questioning the potentialities of gaming...
SDN-enabled OPS with QoS guarantee for reconfigurable virtual data center networks
Miao, W.; Agraz, F.; Peng, S.; Spadaro, S.; Bernini, G.; Perelló, J.; Zervas, G.; Nejabati, R.; Ciulli, Nicola; Simeonidou, D.; Dorren, H.; Calabretta, N.
2015-01-01
Optical packet switching (OPS) can enhance the performance of data center networks (DCNs)by providing fast and large-capacity switching capability. Benefiting from the software-defined networking (SDN) control plane, which could update the look-up-table (LUT) of the OPS, virtual DCNs can be flexibly
Exploiting the ALICE HLT for PROOF by scheduling of Virtual Machines
International Nuclear Information System (INIS)
Meoni, Marco; Boettger, Stefan; Zelnicek, Pierre; Kebschull, Udo; Lindenstruth, Volker
2011-01-01
The HLT (High-Level Trigger) group of the ALICE experiment at the LHC has prepared a virtual Parallel ROOT Facility (PROOF) enabled cluster (HAF - HLT Analysis Facility) for fast physics analysis, detector calibration and reconstruction of data samples. The HLT-Cluster currently consists of 2860 CPU cores and 175TB of storage. Its purpose is the online filtering of the relevant part of data produced by the particle detector. However, data taking is not running continuously and exploiting unused cluster resources for other applications is highly desirable and improves the usage-cost ratio of the HLT cluster. As such, unused computing resources are dedicated to a PROOF-enabled virtual cluster available to the entire collaboration. This setup is especially aimed at the prototyping phase of analyses that need a high number of development iterations and a short response time, e.g. tuning of analysis cuts, calibration and alignment. HAF machines are enabled and disabled upon user request to start or complete analysis tasks. This is achieved by a virtual machine scheduling framework which dynamically assigns and migrates virtual machines running PROOF workers to unused physical resources. Using this approach we extend the HLT usage scheme to running both online and offline computing, thereby optimizing the resource usage.
Mobile devices, Virtual Reality, Augmented Reality, and Digital Geoscience Education.
Crompton, H.; De Paor, D. G.; Whitmeyer, S. J.; Bentley, C.
2016-12-01
Mobile devices are playing an increasing role in geoscience education. Affordances include instructor-student communication and class management in large classrooms, virtual and augmented reality applications, digital mapping, and crowd-sourcing. Mobile technologies have spawned the sub field of mobile learning or m-learning, which is defined as learning across multiple contexts, through social and content interactions. Geoscientists have traditionally engaged in non-digital mobile learning via fieldwork, but digital devices are greatly extending the possibilities, especially for non-traditional students. Smartphones and tablets are the most common devices but smart glasses such as Pivothead enable live streaming of a first-person view (see for example, https://youtu.be/gWrDaYP5w58). Virtual reality headsets such as Google Cardboard create an immersive virtual field experience and digital imagery such as GigaPan and Structure from Motion enables instructors and/or students to create virtual specimens and outcrops that are sharable across the globe. Whereas virtual reality (VR) replaces the real world with a virtual representation, augmented reality (AR) overlays digital data on the live scene visible to the user in real time. We have previously reported on our use of the AR application called FreshAiR for geoscientific "egg hunts." The popularity of Pokémon Go demonstrates the potential of AR for mobile learning in the geosciences.
International Nuclear Information System (INIS)
Melo, Roberto Correia de
2009-01-01
This academic work explains a general view of virtual laboratories (VL) and collaborative virtual environments (CVE) (called, together, a VL/CVE set), focusing their technological features and analyzing the common cognitive features of their users. Also is presented a detailed description of VL/CVE VirRAD (Virtual Radiopharmacy), created specially to connect and support the international radiopharmacy community around the world, and is explained an analysis of their users' cognitive profile, under the perspective of two of the most important cognitive theories of the 20th century: multiple intelligences, by Howard Gardner, and mindful learning, by Ellen Langer. Conclusions from this study has been incorporated, as feature enhancements, to a software prototype created based upon VirRAD software solution, and the hardcopy of their screens is exposed at the end of this work. It is also an essential idea that the conclusions of this work are relevant to any VL/CVE environment. (author)
Carpenter, Kristy A; Huang, Xudong
2018-06-07
Virtual Screening (VS) has emerged as an important tool in the drug development process, as it conducts efficient in silico searches over millions of compounds, ultimately increasing yields of potential drug leads. As a subset of Artificial Intelligence (AI), Machine Learning (ML) is a powerful way of conducting VS for drug leads. ML for VS generally involves assembling a filtered training set of compounds, comprised of known actives and inactives. After training the model, it is validated and, if sufficiently accurate, used on previously unseen databases to screen for novel compounds with desired drug target binding activity. The study aims to review ML-based methods used for VS and applications to Alzheimer's disease (AD) drug discovery. To update the current knowledge on ML for VS, we review thorough backgrounds, explanations, and VS applications of the following ML techniques: Naïve Bayes (NB), k-Nearest Neighbors (kNN), Support Vector Machines (SVM), Random Forests (RF), and Artificial Neural Networks (ANN). All techniques have found success in VS, but the future of VS is likely to lean more heavily toward the use of neural networks - and more specifically, Convolutional Neural Networks (CNN), which are a subset of ANN that utilize convolution. We additionally conceptualize a work flow for conducting ML-based VS for potential therapeutics of for AD, a complex neurodegenerative disease with no known cure and prevention. This both serves as an example of how to apply the concepts introduced earlier in the review and as a potential workflow for future implementation. Different ML techniques are powerful tools for VS, and they have advantages and disadvantages albeit. ML-based VS can be applied to AD drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
A survey of middleware for sensor and network virtualization.
Khalid, Zubair; Fisal, Norsheila; Rozaini, Mohd
2014-12-12
Wireless Sensor Network (WSN) is leading to a new paradigm of Internet of Everything (IoE). WSNs have a wide range of applications but are usually deployed in a particular application. However, the future of WSNs lies in the aggregation and allocation of resources, serving diverse applications. WSN virtualization by the middleware is an emerging concept that enables aggregation of multiple independent heterogeneous devices, networks, radios and software platforms; and enhancing application development. WSN virtualization, middleware can further be categorized into sensor virtualization and network virtualization. Middleware for WSN virtualization poses several challenges like efficient decoupling of networks, devices and software. In this paper efforts have been put forward to bring an overview of the previous and current middleware designs for WSN virtualization, the design goals, software architectures, abstracted services, testbeds and programming techniques. Furthermore, the paper also presents the proposed model, challenges and future opportunities for further research in the middleware designs for WSN virtualization.
A Survey of Middleware for Sensor and Network Virtualization
Khalid, Zubair; Fisal, Norsheila; Rozaini, Mohd.
2014-01-01
Wireless Sensor Network (WSN) is leading to a new paradigm of Internet of Everything (IoE). WSNs have a wide range of applications but are usually deployed in a particular application. However, the future of WSNs lies in the aggregation and allocation of resources, serving diverse applications. WSN virtualization by the middleware is an emerging concept that enables aggregation of multiple independent heterogeneous devices, networks, radios and software platforms; and enhancing application development. WSN virtualization, middleware can further be categorized into sensor virtualization and network virtualization. Middleware for WSN virtualization poses several challenges like efficient decoupling of networks, devices and software. In this paper efforts have been put forward to bring an overview of the previous and current middleware designs for WSN virtualization, the design goals, software architectures, abstracted services, testbeds and programming techniques. Furthermore, the paper also presents the proposed model, challenges and future opportunities for further research in the middleware designs for WSN virtualization. PMID:25615737
Brunner, Stefan; Delcourt, David
2008-01-01
In the only book that completely covers ScreenOS, six key members of Juniper Network's ScreenOS development team help you troubleshoot secure networks using ScreenOS firewall appliances. Over 200 recipes address a wide range of security issues, provide step-by-step solutions, and include discussions of why the recipes work, so you can easily set up and keep ScreenOS systems on track. The easy-to-follow format enables you to find the topic and specific recipe you need right away.
Speculations on the representation of architecture in virtual reality
DEFF Research Database (Denmark)
Hermund, Anders; Klint, Lars; Bundgård, Ture Slot
2017-01-01
to the visual field of perception. However, this should not necessarily imply an acceptance of the dominance of vision over the other senses, and the much-criticized retinal architecture with its inherent loss of plasticity. Recent neurology studies indicate that 3D representation models in virtual reality......This paper discusses the present and future possibilities of representation models of architecture in new media such as virtual reality, seen in the broader context of tradition, perception, and neurology. Through comparative studies of real and virtual scenarios using eye tracking, the paper...... are less demanding on the brain’s working memory than 3D models seen on flat two-dimensional screens. This paper suggests that virtual reality representational architectural models can, if used correctly, significantly improve the imaginative role of architectural representation....
Learning Icelandic Language and Culture in Virtual Reykjavik: Starting to Talk
Bédi, Branislav; Arnbjörnsdóttir, Birna; Vilhjálmsson, Hannes Högni; Helgadóttir, Hafdís Erla; Ólafsson, Stefán; Björgvinsson, Elías
2016-01-01
This paper describes how beginners of Icelandic as a foreign and second language responded to playing the first scene in Virtual Reykjavik, a video game-like environment where learners interact with virtual characters--Embodied Conversational Agents (ECAs). This game enables learners to practice speaking and listening skills, to learn about the…
Astronomical Research Using Virtual Observatories
Directory of Open Access Journals (Sweden)
M Tanaka
2010-01-01
Full Text Available The Virtual Observatory (VO for Astronomy is a framework that empowers astronomical research by providing standard methods to find, access, and utilize astronomical data archives distributed around the world. VO projects in the world have been strenuously developing VO software tools and/or portal systems. Interoperability among VO projects has been achieved with the VO standard protocols defined by the International Virtual Observatory Alliance (IVOA. As a result, VO technologies are now used in obtaining astronomical research results from a huge amount of data. We describe typical examples of astronomical research enabled by the astronomical VO, and describe how the VO technologies are used in the research.
Shale-gas wells as virtual storage for supporting intermittent renewables
International Nuclear Information System (INIS)
Knudsen, Brage Rugstad; Foss, Bjarne
2017-01-01
Mature shale-gas wells possess a property that enables cyclic production and shut-in without incurring revenue losses. Based on this property, we suggest that fields with mature shale-gas wells may act as virtual gas storage for supplying fast-ramping gas power plants which balance intermittent renewable generation. By enabling gas supply to power plants to circumvent intermediate third-party storage, we argue that the proposed integration facilitates demand-driven gas production, and discuss how the scheme may support utilization of renewables and reduce supply-related greenhouse-gas emissions in electricity generation. - Highlights: • A novel integration strategy of shale gas and renewable electricity generation. • Mature shale-gas wells enable shut-ins without incurring revenue losses. • This property enables the use mature shale-gas wells as virtual gas storage. • Proposed scheme facilitates demand-driven gas production. • Omitting intermediate gas storage reduces GHG emissions from producer to end-user.
Virtual materiality, potentiality and gendered subjectivity
DEFF Research Database (Denmark)
Søndergaard, Dorte Marie
How do we conceptualize virtual materiality, in terms of for instance avatars and weapons in computer games, virtual discourse, subjectivity and the enactment of masculinity as phenomena intra-acting with real life materiality, discourse, subjectivity and masculinity in children’s everyday lives......? How do we understand the intra-activity of such elements in children’s night dreams? These are some of the questions discussed in this paper. I bring together Karen Barad’s agential realism and Giorgi Agamben’s concept of potentiality to enable and refine an analytical approach to real......-virtual enactments, thereby questioning the potentialities of gaming, of movies and of dreams as they enter intra-activities in the comprehensive set of apparatuses that enact gendered agency and relational practices. The analyses and conceptual refinements are based on empirical cases involving interviews...
Investigation of tracking systems properties in CAVE-type virtual reality systems
Szymaniak, Magda; Mazikowski, Adam; Meironke, Michał
2017-08-01
In recent years, many scientific and industrial centers in the world developed a virtual reality systems or laboratories. One of the most advanced solutions are Immersive 3D Visualization Lab (I3DVL), a CAVE-type (Cave Automatic Virtual Environment) laboratory. It contains two CAVE-type installations: six-screen installation arranged in a form of a cube, and four-screen installation, a simplified version of the previous one. The user feeling of "immersion" and interaction with virtual world depend on many factors, in particular on the accuracy of the tracking system of the user. In this paper properties of the tracking systems applied in I3DVL was investigated. For analysis two parameters were selected: the accuracy of the tracking system and the range of detection of markers by the tracking system in space of the CAVE. Measurements of system accuracy were performed for six-screen installation, equipped with four tracking cameras for three axes: X, Y, Z. Rotation around the Y axis was also analyzed. Measured tracking system shows good linear and rotating accuracy. The biggest issue was the range of the monitoring of markers inside the CAVE. It turned out, that the tracking system lose sight of the markers in the corners of the installation. For comparison, for a simplified version of CAVE (four-screen installation), equipped with eight tracking cameras, this problem was not occur. Obtained results will allow for improvement of cave quality.
Bresso, Emmanuel; Togawa, Roberto; Hammond-Kosack, Kim; Urban, Martin; Maigret, Bernard; Martins, Natalia Florencio
2016-12-15
Fusarium graminearum (FG) is one of the major cereal infecting pathogens causing high economic losses worldwide and resulting in adverse effects on human and animal health. Therefore, the development of new fungicides against FG is an important issue to reduce cereal infection and economic impact. In the strategy for developing new fungicides, a critical step is the identification of new targets against which innovative chemicals weapons can be designed. As several G-protein coupled receptors (GPCRs) are implicated in signaling pathways critical for the fungi development and survival, such proteins could be valuable efficient targets to reduce Fusarium growth and therefore to prevent food contamination. In this study, GPCRs were predicted in the FG proteome using a manually curated pipeline dedicated to the identification of GPCRs. Based on several successive filters, the most appropriate GPCR candidate target for developing new fungicides was selected. Searching for new compounds blocking this particular target requires the knowledge of its 3D-structure. As no experimental X-Ray structure of the selected protein was available, a 3D model was built by homology modeling. The model quality and stability was checked by 100 ns of molecular dynamics simulations. Two stable conformations representative of the conformational families of the protein were extracted from the 100 ns simulation and were used for an ensemble docking campaign. The model quality and stability was checked by 100 ns of molecular dynamics simulations previously to the virtual screening step. The virtual screening step comprised the exploration of a chemical library with 11,000 compounds that were docked to the GPCR model. Among these compounds, we selected the ten top-ranked nontoxic molecules proposed to be experimentally tested to validate the in silico simulation. This study provides an integrated process merging genomics, structural bioinformatics and drug design for proposing innovative
Energy Technology Data Exchange (ETDEWEB)
Freitas, Victor Goncalves Gloria
2016-07-01
One of the biggest problems in the nuclear area are still the radioactive waste generated in the various applications of this form of energy, all these tailings are stored in warehouses that often are monitored and restructured for better allocation of then. These tailings are stored until it is safe to release into the environment. This work presents a methodology based on virtual reality, for the development of virtual deposits of radioactive waste in order to enable virtual simulations in these deposits. As application will be developed virtually the nuclear waste repository located at the Institute of Nuclear Engineering IEN/CNEN. The development of a virtual warehouse, more specifically, makes it possible to simulate/train the allocation and reallocation of materials with low and medium level of radioactivity, seen the possibility of locomotion of virtual objects and dynamic calculation of the rate of radiation in this environment. Using this methodology it also possible know the accumulated dose, by the virtual character, during the procedures run in the virtual environment. (author)
Collaboration and Dialogue in Virtual Reality
Jensen, Camilla Gyldendahl
2017-01-01
"Virtual reality" adds a new dimension to problem-based learning (PBL) environments in the architecture and building construction educations, where a realistic and lifelike presence in a building enables students to assess and discuss how the various solutions interact with each other. Combined with "Building Information…
Virtual Rewards for Driving Green
Pritchard, Josh
2010-01-01
Carbon dioxide from automobiles is a major contributor to global climate change. In "Virtual Rewards for Driving Green," Josh Pritchard proposes a computer application that will enable fuel-efficient drivers to earn "green" dollars with which to buy digital merchandise on the Web. Can getting items that exist only in cyberspace actually change a…
Meal-Maker: A Virtual Meal Preparation Environment for Children with Cerebral Palsy
Kirshner, Sharon; Weiss, Patrice L.; Tirosh, Emanuel
2011-01-01
Virtual reality (VR) technology enables evaluation and practice of specific skills in a motivating, user-friendly and safe way. The implementation of virtual game environments within clinical settings has increased substantially in recent years. However, the psychometric properties and feasibility of many applications have not been fully…
DockoMatic: automated peptide analog creation for high throughput virtual screening.
Jacob, Reed B; Bullock, Casey W; Andersen, Tim; McDougal, Owen M
2011-10-01
The purpose of this manuscript is threefold: (1) to describe an update to DockoMatic that allows the user to generate cyclic peptide analog structure files based on protein database (pdb) files, (2) to test the accuracy of the peptide analog structure generation utility, and (3) to evaluate the high throughput capacity of DockoMatic. The DockoMatic graphical user interface interfaces with the software program Treepack to create user defined peptide analogs. To validate this approach, DockoMatic produced cyclic peptide analogs were tested for three-dimensional structure consistency and binding affinity against four experimentally determined peptide structure files available in the Research Collaboratory for Structural Bioinformatics database. The peptides used to evaluate this new functionality were alpha-conotoxins ImI, PnIA, and their published analogs. Peptide analogs were generated by DockoMatic and tested for their ability to bind to X-ray crystal structure models of the acetylcholine binding protein originating from Aplysia californica. The results, consisting of more than 300 simulations, demonstrate that DockoMatic predicts the binding energy of peptide structures to within 3.5 kcal mol(-1), and the orientation of bound ligand compares to within 1.8 Å root mean square deviation for ligand structures as compared to experimental data. Evaluation of high throughput virtual screening capacity demonstrated that Dockomatic can collect, evaluate, and summarize the output of 10,000 AutoDock jobs in less than 2 hours of computational time, while 100,000 jobs requires approximately 15 hours and 1,000,000 jobs is estimated to take up to a week. Copyright © 2011 Wiley Periodicals, Inc.
Abercrombie, S. P.; Menzies, A.; Goddard, C.
2017-12-01
Virtual and augmented reality enable scientists to visualize environments that are very difficult, or even impossible to visit, such as the surface of Mars. A useful immersive visualization begins with a high quality reconstruction of the environment under study. This presentation will discuss a photogrammetry pipeline developed at the Jet Propulsion Laboratory to reconstruct 3D models of the surface of Mars using stereo images sent back to Earth by the Curiosity Mars rover. The resulting models are used to support a virtual reality tool (OnSight) that allows scientists and engineers to visualize the surface of Mars as if they were standing on the red planet. Images of Mars present challenges to existing scene reconstruction solutions. Surface images of Mars are sparse with minimal overlap, and are often taken from extremely different viewpoints. In addition, the specialized cameras used by Mars rovers are significantly different than consumer cameras, and GPS localization data is not available on Mars. This presentation will discuss scene reconstruction with an emphasis on coping with limited input data, and on creating models suitable for rendering in virtual reality at high frame rate.
Chimenti, Michael S; Bulfer, Stacie L; Neitz, R Jeffrey; Renslo, Adam R; Jacobson, Matthew P; James, Thomas L; Arkin, Michelle R; Kelly, Mark J S
2015-07-01
The ubiquitous AAA+ ATPase p97 functions as a dynamic molecular machine driving several cellular processes. It is essential in regulating protein homeostasis, and it represents a potential drug target for cancer, particularly when there is a greater reliance on the endoplasmic reticulum-associated protein degradation pathway and ubiquitin-proteasome pathway to degrade an overabundance of secreted proteins. Here, we report a case study for using fragment-based ligand design approaches against this large and dynamic hexamer, which has multiple potential binding sites for small molecules. A screen of a fragment library was conducted by surface plasmon resonance (SPR) and followed up by nuclear magnetic resonance (NMR), two complementary biophysical techniques. Virtual screening was also carried out to examine possible binding sites for the experimental hits and evaluate the potential utility of fragment docking for this target. Out of this effort, 13 fragments were discovered that showed reversible binding with affinities between 140 µM and 1 mM, binding stoichiometries of 1:1 or 2:1, and good ligand efficiencies. Structural data for fragment-protein interactions were obtained with residue-specific [U-(2)H] (13)CH3-methyl-labeling NMR strategies, and these data were compared to poses from docking. The combination of virtual screening, SPR, and NMR enabled us to find and validate a number of interesting fragment hits and allowed us to gain an understanding of the structural nature of fragment binding. © 2015 Society for Laboratory Automation and Screening.
Energy Technology Data Exchange (ETDEWEB)
Sirenko, Oksana, E-mail: oksana.sirenko@moldev.com [Molecular Devices LLC, Sunnyvale, CA 94089 (United States); Cromwell, Evan F., E-mail: evan.cromwell@moldev.com [Molecular Devices LLC, Sunnyvale, CA 94089 (United States); Crittenden, Carole [Molecular Devices LLC, Sunnyvale, CA 94089 (United States); Wignall, Jessica A. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Wright, Fred A. [Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599 (United States); Rusyn, Ivan [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)
2013-12-15
Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise for screening during early drug development. Here, we tested a hypothesis that in vitro assessment of multiple cardiomyocyte physiological parameters enables predictive and mechanistically-interpretable evaluation of cardiotoxicity in a high-throughput format. Human iPSC-derived cardiomyocytes were exposed for 30 min or 24 h to 131 drugs, positive (107) and negative (24) for in vivo cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates. Fast kinetic imaging was used to monitor changes in cardiomyocyte function using intracellular Ca{sup 2+} flux readouts synchronous with beating, and cell viability. A number of physiological parameters of cardiomyocyte beating, such as beat rate, peak shape (amplitude, width, raise, decay, etc.) and regularity were collected using automated data analysis. Concentration–response profiles were evaluated using logistic modeling to derive a benchmark concentration (BMC) point-of-departure value, based on one standard deviation departure from the estimated baseline in vehicle (0.3% dimethyl sulfoxide)-treated cells. BMC values were used for cardiotoxicity classification and ranking of compounds. Beat rate and several peak shape parameters were found to be good predictors, while cell viability had poor classification accuracy. In addition, we applied the Toxicological Prioritization Index (ToxPi) approach to integrate and display data across many collected parameters, to derive “cardiosafety” ranking of tested compounds. Multi-parameter screening of beating profiles allows for cardiotoxicity risk assessment and identification of specific patterns defining mechanism-specific effects. These data and analysis methods may be used widely for compound screening and early safety evaluation in drug development. - Highlights: • Induced pluripotent stem cell-derived cardiomyocytes are promising in vitro models. • We tested if evaluation
International Nuclear Information System (INIS)
Sirenko, Oksana; Cromwell, Evan F.; Crittenden, Carole; Wignall, Jessica A.; Wright, Fred A.; Rusyn, Ivan
2013-01-01
Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise for screening during early drug development. Here, we tested a hypothesis that in vitro assessment of multiple cardiomyocyte physiological parameters enables predictive and mechanistically-interpretable evaluation of cardiotoxicity in a high-throughput format. Human iPSC-derived cardiomyocytes were exposed for 30 min or 24 h to 131 drugs, positive (107) and negative (24) for in vivo cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates. Fast kinetic imaging was used to monitor changes in cardiomyocyte function using intracellular Ca 2+ flux readouts synchronous with beating, and cell viability. A number of physiological parameters of cardiomyocyte beating, such as beat rate, peak shape (amplitude, width, raise, decay, etc.) and regularity were collected using automated data analysis. Concentration–response profiles were evaluated using logistic modeling to derive a benchmark concentration (BMC) point-of-departure value, based on one standard deviation departure from the estimated baseline in vehicle (0.3% dimethyl sulfoxide)-treated cells. BMC values were used for cardiotoxicity classification and ranking of compounds. Beat rate and several peak shape parameters were found to be good predictors, while cell viability had poor classification accuracy. In addition, we applied the Toxicological Prioritization Index (ToxPi) approach to integrate and display data across many collected parameters, to derive “cardiosafety” ranking of tested compounds. Multi-parameter screening of beating profiles allows for cardiotoxicity risk assessment and identification of specific patterns defining mechanism-specific effects. These data and analysis methods may be used widely for compound screening and early safety evaluation in drug development. - Highlights: • Induced pluripotent stem cell-derived cardiomyocytes are promising in vitro models. • We tested if evaluation of
IVSPlat 1.0: an integrated virtual screening platform with a molecular graphical interface.
Sun, Yin Xue; Huang, Yan Xin; Li, Feng Li; Wang, Hong Yan; Fan, Cong; Bao, Yong Li; Sun, Lu Guo; Ma, Zhi Qiang; Kong, Jun; Li, Yu Xin
2012-01-05
The virtual screening (VS) of lead compounds using molecular docking and pharmacophore detection is now an important tool in drug discovery. VS tasks typically require a combination of several software tools and a molecular graphics system. Thus, the integration of all the requisite tools in a single operating environment could reduce the complexity of running VS experiments. However, only a few freely available integrated software platforms have been developed. A free open-source platform, IVSPlat 1.0, was developed in this study for the management and automation of VS tasks. We integrated several VS-related programs into a molecular graphics system to provide a comprehensive platform for the solution of VS tasks based on molecular docking, pharmacophore detection, and a combination of both methods. This tool can be used to visualize intermediate and final results of the VS execution, while also providing a clustering tool for the analysis of VS results. A case study was conducted to demonstrate the applicability of this platform. IVSPlat 1.0 provides a plug-in-based solution for the management, automation, and visualization of VS tasks. IVSPlat 1.0 is an open framework that allows the integration of extra software to extend its functionality and modified versions can be freely distributed. The open source code and documentation are available at http://kyc.nenu.edu.cn/IVSPlat/.
Kibria, Muhammad Golam; Ali, Sajjad; Jarwar, Muhammad Aslam; Kumar, Sunil; Chong, Ilyoung
2017-09-22
Due to a very large number of connected virtual objects in the surrounding environment, intelligent service features in the Internet of Things requires the reuse of existing virtual objects and composite virtual objects. If a new virtual object is created for each new service request, then the number of virtual object would increase exponentially. The Web of Objects applies the principle of service modularity in terms of virtual objects and composite virtual objects. Service modularity is a key concept in the Web Objects-Enabled Internet of Things (IoT) environment which allows for the reuse of existing virtual objects and composite virtual objects in heterogeneous ontologies. In the case of similar service requests occurring at the same, or different locations, the already-instantiated virtual objects and their composites that exist in the same, or different ontologies can be reused. In this case, similar types of virtual objects and composite virtual objects are searched and matched. Their reuse avoids duplication under similar circumstances, and reduces the time it takes to search and instantiate them from their repositories, where similar functionalities are provided by similar types of virtual objects and their composites. Controlling and maintaining a virtual object means controlling and maintaining a real-world object in the real world. Even though the functional costs of virtual objects are just a fraction of those for deploying and maintaining real-world objects, this article focuses on reusing virtual objects and composite virtual objects, as well as discusses similarity matching of virtual objects and composite virtual objects. This article proposes a logistic model that supports service modularity for the promotion of reusability in the Web Objects-enabled IoT environment. Necessary functional components and a flowchart of an algorithm for reusing composite virtual objects are discussed. Also, to realize the service modularity, a use case scenario is
Chen, Charlie C.; Wu, Jiinpo; Yang, Samuel C.; Tsou, Hsin-Yi
2008-01-01
Virtual teams enabled by information and communications technologies (ICT) are increasingly being adopted not only by for-profit organizations but also by education institutions as well. This study investigates what contributes to the success of virtual learning teams. Specifically, we examine the issue of leadership in virtual learning teams. The…
The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure
Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik
2006-01-01
Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…
Damm-Ganamet, Kelly L; Bembenek, Scott D; Venable, Jennifer W; Castro, Glenda G; Mangelschots, Lieve; Peeters, Daniëlle C G; Mcallister, Heather M; Edwards, James P; Disepio, Daniel; Mirzadegan, Taraneh
2016-05-12
Here, we report a high-throughput virtual screening (HTVS) study using phosphoinositide 3-kinase (both PI3Kγ and PI3Kδ). Our initial HTVS results of the Janssen corporate database identified small focused libraries with hit rates at 50% inhibition showing a 50-fold increase over those from a HTS (high-throughput screen). Further, applying constraints based on "chemically intuitive" hydrogen bonds and/or positional requirements resulted in a substantial improvement in the hit rates (versus no constraints) and reduced docking time. While we find that docking scoring functions are not capable of providing a reliable relative ranking of a set of compounds, a prioritization of groups of compounds (e.g., low, medium, and high) does emerge, which allows for the chemistry efforts to be quickly focused on the most viable candidates. Thus, this illustrates that it is not always necessary to have a high correlation between a computational score and the experimental data to impact the drug discovery process.
Optimizing infrastructure for software testing using virtualization
International Nuclear Information System (INIS)
Khalid, O.; Shaikh, A.; Copy, B.
2012-01-01
Virtualization technology and cloud computing have brought a paradigm shift in the way we utilize, deploy and manage computer resources. They allow fast deployment of multiple operating system as containers on physical machines which can be either discarded after use or check-pointed for later re-deployment. At European Organization for Nuclear Research (CERN), we have been using virtualization technology to quickly setup virtual machines for our developers with pre-configured software to enable them to quickly test/deploy a new version of a software patch for a given application. This paper reports both on the techniques that have been used to setup a private cloud on a commodity hardware and also presents the optimization techniques we used to remove deployment specific performance bottlenecks. (authors)
Virtual environments for scene of crime reconstruction and analysis
Howard, Toby L. J.; Murta, Alan D.; Gibson, Simon
2000-02-01
This paper describes research conducted in collaboration with Greater Manchester Police (UK), to evalute the utility of Virtual Environments for scene of crime analysis, forensic investigation, and law enforcement briefing and training. We present an illustrated case study of the construction of a high-fidelity virtual environment, intended to match a particular real-life crime scene as closely as possible. We describe and evaluate the combination of several approaches including: the use of the Manchester Scene Description Language for constructing complex geometrical models; the application of a radiosity rendering algorithm with several novel features based on human perceptual consideration; texture extraction from forensic photography; and experiments with interactive walkthroughs and large-screen stereoscopic display of the virtual environment implemented using the MAVERIK system. We also discuss the potential applications of Virtual Environment techniques in the Law Enforcement and Forensic communities.
Sun, Huiyong; Pan, Peichen; Tian, Sheng; Xu, Lei; Kong, Xiaotian; Li, Youyong; Dan Li; Hou, Tingjun
2016-04-22
The MIEC-SVM approach, which combines molecular interaction energy components (MIEC) derived from free energy decomposition and support vector machine (SVM), has been found effective in capturing the energetic patterns of protein-peptide recognition. However, the performance of this approach in identifying small molecule inhibitors of drug targets has not been well assessed and validated by experiments. Thereafter, by combining different model construction protocols, the issues related to developing best MIEC-SVM models were firstly discussed upon three kinase targets (ABL, ALK, and BRAF). As for the investigated targets, the optimized MIEC-SVM models performed much better than the models based on the default SVM parameters and Autodock for the tested datasets. Then, the proposed strategy was utilized to screen the Specs database for discovering potential inhibitors of the ALK kinase. The experimental results showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening.
Sulistyawati, Indah; Sulistyo Dwi K., P.; Ichsan, Mochammad
2016-03-01
Hepatitis C is one of the major causes of chronic liver failure that caused by Hepatitis C Virus (HCV). Preventing the progression of HCV's replication through the inhibition of The RNA polymerase NS5B of Hepatitis C virus (NS5B) can be achieved via 4 binding regions: Site I (Thumb I), Site II (Thumb II), Site III (Palm I), and Site IV (Palm II). The aim of this research is to identify a candidate of NS5B inhibitor as an alternative for Hepatitis C treatment. An NS5B's 3D structure (PDB ID = 3D5M) used in this study has met some criteria of a good model to be used in virtual screening againts iPPI-lib using MTiOpenScreen webserver. The top two natural compounds resulted here then docked using Pyrix 0.8 and discovered trans-6-Benzamido-2-methyldecahydroisoquinoline (-9,1kcal/mol) and 2,4-dichloro-5-[4-(2 methoxyphenyl) piperazine-1-carbonyl]-N-[3-(trifluoromethyl)phenyl] benzenesulfonamide (9,4 kcal/mol) can bind to Tyr448 similar with all three established inhibitors, such as setrobuvir (-11,4 kcal/mol; site 3 inhibitor), CHEMBL379677 (-9,1 kcal/mol; site 1 inhibitor), and nesbuvir (-7,7 kcal/mol; site 4 inhibitor). The results of this study are relatively still needs to be tested, both in vitro and in vivo, in order to obtain more comprehensive knowledges as a follow-up of this predictive study.
A Model of and for Virtual Projects
Garud, R.; Kumaraswamy, A.; Tuertscher, P.R.; Cattani, G.; Ferriani, S.; Frederiksen, L.; Täube, F.
2011-01-01
We examine how digital technologies enable distributed actors to collaborate asynchronously on virtual projects. We use Wikipedia and associated wiki digital technology as the research site for our exploration. Our probe of the emergence of Wikipedia articles highlights a distinctive property of
Directory of Open Access Journals (Sweden)
Guoqing Zhang
2018-03-01
Full Text Available Indoleamine 2,3-dioxygenase 1 (IDO1 is an intracellular monomeric heme-containing enzyme that catalyzes the first and the rate limiting step in catabolism of tryptophan via the kynurenine (KYN pathway, which plays a significant role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for anticancer therapy and chronic viral infections. In the present study, a class of IDO1 inhibitors with novel scaffolds were identified by virtual screening and biochemical validation, in which the compound DC-I028 shows moderate IDO1 inhibitory activity with an IC50 of 21.61 μM on enzymatic level and 89.11 μM on HeLa cell. In the following hit expansion stage, DC-I02806, an analog of DC-I028, showed better inhibitory activity with IC50 about 18 μM on both enzymatic level and cellular level. The structure–activity relationship (SAR of DC-I028 and its analogs was then discussed based on the molecular docking result. The novel IDO1 inhibitors of DC-I028 and its analogs may provide useful clues for IDO1 inhibitor development.
Zhang, Guoqing; Xing, Jing; Wang, Yulan; Wang, Lihao; Ye, Yan; Lu, Dong; Zhao, Jihui; Luo, Xiaomin; Zheng, Mingyue; Yan, Shiying
2018-01-01
Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular monomeric heme-containing enzyme that catalyzes the first and the rate limiting step in catabolism of tryptophan via the kynurenine (KYN) pathway, which plays a significant role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for anticancer therapy and chronic viral infections. In the present study, a class of IDO1 inhibitors with novel scaffolds were identified by virtual screening and biochemical validation, in which the compound DC-I028 shows moderate IDO1 inhibitory activity with an IC50 of 21.61 μM on enzymatic level and 89.11 μM on HeLa cell. In the following hit expansion stage, DC-I02806, an analog of DC-I028, showed better inhibitory activity with IC50 about 18 μM on both enzymatic level and cellular level. The structure–activity relationship (SAR) of DC-I028 and its analogs was then discussed based on the molecular docking result. The novel IDO1 inhibitors of DC-I028 and its analogs may provide useful clues for IDO1 inhibitor development. PMID:29651242
Directory of Open Access Journals (Sweden)
Yuwei Wang
2017-01-01
Full Text Available The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR, are the main endocrine therapies for prostate cancer (PCa. But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists. In this work, the relationships between the molecular structures and antiandrogenic activities of a series of 7α-substituted dihydrotestosterone derivatives were investigated. The proposed MLR model obtained high predictive ability. The thoroughly validated QSAR model was used to virtually screen new dihydrotestosterones derivatives taken from PubChem, resulting in the finding of novel compounds CID_70128824, CID_70127147, and CID_70126881, whose in silico bioactivities are much higher than the published best one, even higher than bicalutamide. In addition, molecular docking, molecular dynamics (MD simulations, and MM/GBSA have been employed to analyze and compare the binding modes between the novel compounds and AR. Through the analysis of the binding free energy and residue energy decomposition, we concluded that the newly discovered chemicals can in silico bind to AR with similar position and mechanism to the reported active compound and the van der Waals interaction is the main driving force during the binding process.
Bidarra, R.; Kraker, K.J. de; Smelik, R.M.; Tutenel, T.
2010-01-01
Manual content creation for virtual worlds can no longer satisfy the increasing demand arising from areas as entertainment and serious games, simulations, movies, etc. Furthermore, currently deployed modeling tools basically do not scale up: while they become more and more specialized and complex,
Ocular effects of virtual reality headset wear in young adults
Turnbull, Philip R. K.; Phillips, John R.
2017-01-01
Virtual Reality (VR) headsets create immersion by displaying images on screens placed very close to the eyes, which are viewed through high powered lenses. Here we investigate whether this viewing arrangement alters the binocular status of the eyes, and whether it is likely to provide a stimulus for myopia development. We compared binocular status after 40-minute trials in indoor and outdoor environments, in both real and virtual worlds. We also measured the change in thickness of the ocular ...
Speculations on the representation of architecture in virtual reality
DEFF Research Database (Denmark)
Hermund, Anders; Klint, Lars; Bundgård, Ture Slot
2017-01-01
to the visual field of perception. However, this should not necessarily imply an acceptance of the dominance of vision over the other senses, and the much-criticized retinal architecture with its inherent loss of plasticity. Recent neurology studies indicate that 3D representation models in virtual reality...... are less demanding on the brain’s working memory than 3D models seen on flat two-dimensional screens. This paper suggests that virtual reality representational architectural models can, if used correctly, significantly improve the imaginative role of architectural representation....
Valvoda, Jakob T; Assenmacher, Ingo; Dohle, Christian; Kuhlen, Torsten; Bischof, Christian
2003-01-01
We describe a comprehensive software-oriented approach to virtual reality-based neuroscientific systems in order to establish an easy to use framework for neuroscientific assessment and treatment. We have defined a process model and implemented the NeuroVRAC authoring tool for design and execution of experiments in virtual environments. Our system enables the modeling of virtual world objects and the definition of events, which are used to control the experimental process. We have included the virtual test person concept to enhance the sense of presence during the execution of virtual reality-based neuroscientific experiments.
A Design Space for Virtuality-Introduced Internet of Things
Directory of Open Access Journals (Sweden)
Kota Gushima
2017-10-01
Full Text Available Augmented reality (AR and virtual reality (VR technologies have been dramatically expanded in recent years. In the near future, we expect that diverse digital services that employ Internet of Things (IoT technologies enhanced with AR and VR will become more popular. Advanced information technologies will enable the physical world to be fused with the virtual world. These digital services will be advanced via virtuality, which means that things that do not physically exist make people believe in their existence. We propose a design space for digital services that are enhanced via virtuality based on insights extracted from three case studies that we have developed and from discussions in focus groups that analyze how existing commercial IoT products proposed in a commercial crowdfunding platform, Kickstarter, could be enhanced through virtuality. The derived design space offers three dimensions to design a digital service to fuse IoT technologies with virtuality: (1 Taxonomy of IoT; (2 Visualizing Level, and (3 Virtuality Level. The design space will help IoT-based digital service designers to develop advanced future IoT products that incorporate virtuality.
Joint Orchestration of Cloud-Based Microservices and Virtual Network Functions
Kouchaksaraei, Hadi Razzaghi; Karl, Holger
2018-01-01
Recent studies show the increasing popularity of distributed cloud applications, which are composed of multiple microservices. Besides their known benefits, microservice architecture also enables to mix and match cloud applications and Network Function Virtualization (NFV) services (service chains), which are composed of Virtual Network Functions (VNFs). Provisioning complex services containing VNFs and microservices in a combined NFV/cloud platform can enhance service quality and optimise co...
Virtual Travel Agencies - Tourist Value through Travel Information Systems
Anckar, Bill
1999-01-01
Anckar, B. (1999), ?Virtual Travel Agencies - Tourist Value through Travel Information Systems?. IAMSR Research Report 5/99. Institute for Advanced Management Systems Research, ?bo Akademi University. As electronic commerce enables the tourist service providers to sell their products directly to the consumer, travel agencies are faced with the imminent threat of being by-passed in the travel industry chain in the information age. This paper suggests that virtual travel agencies can compete su...
DockoMatic 2.0: high throughput inverse virtual screening and homology modeling.
Bullock, Casey; Cornia, Nic; Jacob, Reed; Remm, Andrew; Peavey, Thomas; Weekes, Ken; Mallory, Chris; Oxford, Julia T; McDougal, Owen M; Andersen, Timothy L
2013-08-26
DockoMatic is a free and open source application that unifies a suite of software programs within a user-friendly graphical user interface (GUI) to facilitate molecular docking experiments. Here we describe the release of DockoMatic 2.0; significant software advances include the ability to (1) conduct high throughput inverse virtual screening (IVS); (2) construct 3D homology models; and (3) customize the user interface. Users can now efficiently setup, start, and manage IVS experiments through the DockoMatic GUI by specifying receptor(s), ligand(s), grid parameter file(s), and docking engine (either AutoDock or AutoDock Vina). DockoMatic automatically generates the needed experiment input files and output directories and allows the user to manage and monitor job progress. Upon job completion, a summary of results is generated by Dockomatic to facilitate interpretation by the user. DockoMatic functionality has also been expanded to facilitate the construction of 3D protein homology models using the Timely Integrated Modeler (TIM) wizard. The wizard TIM provides an interface that accesses the basic local alignment search tool (BLAST) and MODELER programs and guides the user through the necessary steps to easily and efficiently create 3D homology models for biomacromolecular structures. The DockoMatic GUI can be customized by the user, and the software design makes it relatively easy to integrate additional docking engines, scoring functions, or third party programs. DockoMatic is a free comprehensive molecular docking software program for all levels of scientists in both research and education.
Virtual Lab for Wireless Sensor Networks
Directory of Open Access Journals (Sweden)
PICOVICI, D.
2008-06-01
Full Text Available This article details an experimental system developed to enhance the education and research in the area of wireless networks technologies. The system referred, as Virtual Lab (VL is primarily targeting first time users or users with limited experience in programming and using wireless sensor networks. The VL enables a set of predefined sensor networks to be remotely accessible and controlled for constructive and time-efficient experimentation. In order to facilitate the user's wireless sensor applications, the VL is using three main components: a a Virtual Lab Motes (VLM, representing the wireless sensor, b a Virtual Lab Client (VLC, representing the user's tool to interact with the VLM and c a Virtual Lab Server (VLS representing the software link between the VLM and VLC. The concept has been proven using the moteiv produced Tmote Sky modules. Initial experimental use clearly demonstrates that the VL approach reduces dramatically the learning curve involved in programming and using the associated wireless sensor nodes. In addition the VL allows the user's focus to be directed towards the experiment and not towards the software programming challenges.
Screening of a virtual mirror-image library of natural products.
Noguchi, Taro; Oishi, Shinya; Honda, Kaori; Kondoh, Yasumitsu; Saito, Tamio; Ohno, Hiroaki; Osada, Hiroyuki; Fujii, Nobutaka
2016-06-08
We established a facile access to an unexplored mirror-image library of chiral natural product derivatives using d-protein technology. In this process, two chemical syntheses of mirror-image substances including a target protein and hit compound(s) allow the lead discovery from a virtual mirror-image library without the synthesis of numerous mirror-image compounds.
The Use of Virtual Reality Tools in the Reading-Language Arts Classroom
Pilgrim, J. Michael; Pilgrim, Jodi
2016-01-01
This article presents virtual reality as a tool for classroom literacy instruction. Building on the traditional use of images as a way to scaffold prior knowledge, we extend this idea to share ways virtual reality enables experiential learning through field trip-like experiences. The use of technology tools such Google Street view, Google…
Directory of Open Access Journals (Sweden)
Riby Abraham Boby
2017-05-01
Full Text Available This article focuses on the implementation details of a portable interactive device called Image-projective Desktop Varnamala Trainer. The device uses a projector to produce a virtual display on a flat surface. For enabling interaction, the information about a user’s hand movement is obtained from a single two-dimensional scanning laser range finder in contrast with a camera sensor used in many earlier applications. A generalized calibration process to obtain exact transformation from projected screen coordinate system to sensor coordinate system is proposed in this article and implemented for enabling interaction. This permits production of large interactive displays with minimal cost. Additionally, it makes the entire system portable, that is, display can be produced on any planar surface like floor, tabletop, and so on. The calibration and its performance have been evaluated by varying screen sizes and the number of points used for calibration. The device was successfully calibrated for different screens. A novel learning-based methodology for predicting a user’s behaviour was then realized to improve the system’s performance. This has been experimentally evaluated, and the overall accuracy of prediction was about 96%. An application was then designed for this set-up to improve the learning of alphabets by the children through an interactive audiovisual feedback system. It uses a game-based methodology to help students learn in a fun way. Currently, it has bilingual (Hindi and English user interface to enable learning of alphabets and elementary mathematics. A user survey was conducted after demonstrating it to school children. The survey results are very encouraging. Additionally, a study to ascertain the improvement in the learning outcome of the children was done. The results clearly indicate an improvement in the learning outcome of the children who used the device over those who did not.
Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna
2013-01-01
Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having
Lee, Jae M; Ku, Jeong H; Jang, Dong P; Kim, Dong H; Choi, Young H; Kim, In Y; Kim, Sun I
2002-06-01
The fear of speaking is often cited as the world's most common social phobia. The rapid growth of computer technology enabled us to use virtual reality (VR) for the treatment of the fear of public speaking. There have been two techniques used to construct a virtual environment for the treatment of the fear of public speaking: model-based and movie-based. Virtual audiences and virtual environments made by model-based technique are unrealistic and unnatural. The movie-based technique has a disadvantage in that each virtual audience cannot be controlled respectively, because all virtual audiences are included in one moving picture file. To address this disadvantage, this paper presents a virtual environment made by using image-based rendering (IBR) and chroma keying simultaneously. IBR enables us to make the virtual environment realistic because the images are stitched panoramically with the photos taken from a digital camera. And the use of chroma keying allows a virtual audience to be controlled individually. In addition, a real-time capture technique was applied in constructing the virtual environment to give the subjects more interaction, in that they can talk with a therapist or another subject.
Tarnanas, Ioannis; Schlee, Winfried; Tsolaki, Magda; Müri, René; Mosimann, Urs; Nef, Tobias
2013-08-06
Dementia is a multifaceted disorder that impairs cognitive functions, such as memory, language, and executive functions necessary to plan, organize, and prioritize tasks required for goal-directed behaviors. In most cases, individuals with dementia experience difficulties interacting with physical and social environments. The purpose of this study was to establish ecological validity and initial construct validity of a fire evacuation Virtual Reality Day-Out Task (VR-DOT) environment based on performance profiles as a screening tool for early dementia. The objectives were (1) to examine the relationships among the performances of 3 groups of participants in the VR-DOT and traditional neuropsychological tests employed to assess executive functions, and (2) to compare the performance of participants with mild Alzheimer's-type dementia (AD) to those with amnestic single-domain mild cognitive impairment (MCI) and healthy controls in the VR-DOT and traditional neuropsychological tests used to assess executive functions. We hypothesized that the 2 cognitively impaired groups would have distinct performance profiles and show significantly impaired independent functioning in ADL compared to the healthy controls. The study population included 3 groups: 72 healthy control elderly participants, 65 amnestic MCI participants, and 68 mild AD participants. A natural user interface framework based on a fire evacuation VR-DOT environment was used for assessing physical and cognitive abilities of seniors over 3 years. VR-DOT focuses on the subtle errors and patterns in performing everyday activities and has the advantage of not depending on a subjective rating of an individual person. We further assessed functional capacity by both neuropsychological tests (including measures of attention, memory, working memory, executive functions, language, and depression). We also evaluated performance in finger tapping, grip strength, stride length, gait speed, and chair stands separately and
Colorectal Cancer Screening (PDQ®)—Patient Version
There are five types of tests that are used to screen for colorectal cancer: fecal occult blood test, sigmoidoscopy, colonoscopy, virtual colonoscopy, and DNA stool test. Learn more about these and other tests in this expert-reviewed summary.
Managing Geographically Dispersed Teams: From Temporary to Permanent Global Virtual Teams
DEFF Research Database (Denmark)
Svane Hansen, Tine; Hope, Alexander John; Moehler, Robert C.
2012-01-01
for organisations to move towards establishing permanent Global Virtual Teams in order to leverage knowledge sharing and cooperation across distance. To close this gap, this paper will set the scene for a research project investigating the changed preconditions for organisations. As daily face-to-face communication......The rise and spread of information communication technologies (ICT) has enabled increasing use of geographically dispersed work teams (Global Virtual Teams). Originally, Global Virtual Teams were mainly organised into temporary projects. Little research has focused on the emergent challenge...... generation of self-lead digital natives, who are already practising virtual relationships and a new approach to work, and currently joining the global workforce; and improved communication technologies. Keywords: Global Virtual teams, ICT, leadership, motivation, self-management, millenials....
Seamless 3D interaction for virtual tables, projection planes, and CAVEs
Encarnacao, L. M.; Bimber, Oliver; Schmalstieg, Dieter; Barton, Robert J., III
2000-08-01
The Virtual Table presents stereoscopic graphics to a user in a workbench-like setting. This device shares with other large- screen display technologies (such as data walls and surround- screen projection systems) the lack of human-centered unencumbered user interfaces and 3D interaction technologies. Such shortcomings present severe limitations to the application of virtual reality (VR) technology to time- critical applications as well as employment scenarios that involve heterogeneous groups of end-users without high levels of computer familiarity and expertise. Traditionally such employment scenarios are common in planning-related application areas such as mission rehearsal and command and control. For these applications, a high grade of flexibility with respect to the system requirements (display and I/O devices) as well as to the ability to seamlessly and intuitively switch between different interaction modalities and interaction are sought. Conventional VR techniques may be insufficient to meet this challenge. This paper presents novel approaches for human-centered interfaces to Virtual Environments focusing on the Virtual Table visual input device. It introduces new paradigms for 3D interaction in virtual environments (VE) for a variety of application areas based on pen-and-clipboard, mirror-in-hand, and magic-lens metaphors, and introduces new concepts for combining VR and augmented reality (AR) techniques. It finally describes approaches toward hybrid and distributed multi-user interaction environments and concludes by hypothesizing on possible use cases for defense applications.
DEFF Research Database (Denmark)
Clausen, Anders; Umair, Aisha; Demazeau, Yves
2017-01-01
A Virtual Power Plant aggregates several Distributed Energy Resources in order to expose them as a single, controllable entity. This enables smaller Distributed Energy Resources to take part in Demand Response programs which traditionally only targeted larger consumers. To date, models for Virtual...
Converged Optical Network and Data Center Virtual Infrastructure Planning
DEFF Research Database (Denmark)
Georgakilas, Konstantinos; Tzanakaki, Anna; Anastasopoulos, Markos
2012-01-01
This paper presents a detailed study of planning virtual infrastructures (VIs) over a physical infrastructure comprising integrated optical network and data center resources with the aim of enabling sharing of physical resources among several virtual operators and services. Through the planning...... process, the VI topology and virtual resources are identified and mapped to the physical resources. Our study assumes a practical VI demand model without any in advance global knowledge of the VI requests that are handled sequentially. Through detailed integer linear program modeling, two objective...... functions—one that minimizes the overall power consumption of the infrastructure and one that minimizes the wavelength utilization—are compared. Both are evaluated for the virtual wavelength path and wavelength path optical network architectures. The first objective results in power consumption savings...
A LEGO paradigm for virtual accelerator concept
International Nuclear Information System (INIS)
Andrianov, S.; Ivanov, A.; Podzyvalov, E.
2012-01-01
The paper considers basic features of a Virtual Accelerator concept based on LEGO paradigm. This concept involves three types of components: different mathematical models for accelerator design problems, integrated beam simulation packages (i. e. COSY, MAD, OptiM and others), and a special class of virtual feedback instruments similar to real control systems (EPICS). All of these components should inter-operate for more complete analysis of control systems and increased fault tolerance. The Virtual Accelerator is an information and computing environment which provides a framework for analysis based on these components that can be combined in different ways. Corresponding distributed computing services establish interaction between mathematical models and low level control system. The general idea of the software implementation is based on the Service-Oriented Architecture (SOA) that allows using cloud computing technology and enables remote access to the information and computing resources. The Virtual Accelerator allows a designer to combine powerful instruments for modeling beam dynamics in a friendly way including both self-developed and well-known packages. In the scope of this concept the following is also proposed: the control system identification, analysis and result verification, visualization as well as virtual feedback for beam line operation. The architecture of the Virtual Accelerator system itself and results of beam dynamics studies are presented. (authors)
Virtual reality technology used to estimate radiation doses in nuclear installations
International Nuclear Information System (INIS)
Augusto, Silas Cordeiro
2008-03-01
The physical integrity of people when walking in places subjected to radiation can be preserved by following some rules. Among these rules are safe limits of radiation level, proximity of radiation sources, time of exposition to radiation sources, and a combination of these factors. In this way, previous training and simulations of operation proceedings to be executed in places subjected to radiation help to better prepare the course in such places, minimizing the absorbed dose. On the other hand, virtual reality is a technology applicable in several areas, enabling the training and simulation of real places and hypothetical scenarios, with a good level of realism, but without danger if compared to the same activities in the real world. As a virtual environment does not presents any health risks, it is possible to train workers beforehand to several operation or maintenance scenarios. In this virtual environment, the dose tax distribution can be visualized, and the dose absorbed by the worker, represented and simulated in the virtual environment by a virtual character (avatar) can be shown. Therefore, the tasks to be done can be better planned, evaluating the workers actions and the performance so to reduce failures and health risks. Finally, this work presents a tool to build and navigate in virtual environments, enabling the training of activities in nuclear facilities. To that end is proposed a methodology to modify and adapt a free game engine. (author)
Making the most of mobility: virtual mentoring and education practitioner professional development
Directory of Open Access Journals (Sweden)
Hazel D. Owen
2015-09-01
Full Text Available Learning provision, including professional learning, needs to embrace mobility (of knowledge, cultures and contexts – physical and cerebral to enable education practitioners to interact locally and globally, engage with new literacies, access rich contexts, and to question, co-construct and collaborate. Virtual mentoring, also known as distance, remote, tele-, cyber- and eMentoring, offers a level of flexibility that enables mentors and mentees to maximise these concepts of mobility. There are Professional Learning and Development (PLD initiatives that offer contextualised, individualised learning experiences via mentoring partnerships and Communities of Practice (CoPs, but not so many that have focussed on virtual mentoring and online CoPs. This article describes a Virtual PLD programme that has been offered in Aotearoa New Zealand from 2009 to date and discusses findings from the associated research study, including benefits that can be specifically equated to the virtual nature of the mentoring and access to the online CoP. Also reported are shifts in mentees’ self-efficacy and perceptions of changes in professional practice.
Multimodality and Design of Interactive Virtual Environments for Creative Collaboration
DEFF Research Database (Denmark)
Gürsimsek, Remzi Ates
. The three-dimensional representation of space and the resources for non-verbal communication enable the users to interact with the digital content in more complex yet engaging ways. However, understanding the communicative resources in virtual spaces with the theoretical tools that are conventionally used...... perspective particularly emphasizes the role of audio-visual resources in co-creating representations for effective collaboration, and the socio-cultural factors in construction of meaningful virtual environments....
Integration of the virtual 3D model of a control system with the virtual controller
Herbuś, K.; Ociepka, P.
2015-11-01
operation of the adopted research object. The carried out work allowed foot the integration of the virtual model of the control system of the tunneling machine with the virtual controller, enabling the verification of its operation.
Li, Lanlan; Wei, Wei; Jia, Wen-Juan; Zhu, Yongchang; Zhang, Yan; Chen, Jiang-Huai; Tian, Jiaqi; Liu, Huanxiang; He, Yong-Xing; Yao, Xiaojun
2017-12-01
Conformational conversion of the normal cellular prion protein, PrPC, into the misfolded isoform, PrPSc, is considered to be a central event in the development of fatal neurodegenerative diseases. Stabilization of prion protein at the normal cellular form (PrPC) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrPC to PrPSc conversion. Compound 3253-0207 that can bind to PrPC with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound 3253-0207 can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrPC to PrPSc.
Massarotti, Alberto; Theeramunkong, Sewan; Mesenzani, Ornella; Caldarelli, Antonio; Genazzani, Armando A; Tron, Gian Cesare
2011-12-01
Tubulin inhibition represents an established target in the field of anticancer research, and over the last 20 years, an intensive search for new antimicrotubule agents has occurred. Indeed, in silico models have been presented that might aid the discovery of novel agents. Among these, a 7-point pharmacophore model has been recently proposed. As a formal proof of this model, we carried out a ligand-based virtual screening on the colchicine-binding site. In vitro testing demonstrated that two compounds displayed a cytotoxic profile on neuroblastoma cancer cells (SH-SY5H) and one had an antitubulinic profile. © 2011 John Wiley & Sons A/S.
Singh, Swati; Khare, Garima; Bahal, Ritika Kar; Ghosh, Prahlad C; Tyagi, Anil K
2018-01-01
Background 7,8-Diaminopelargonic acid synthase (BioA), an enzyme of biotin biosynthesis pathway, is a well-known promising target for anti-tubercular drug development. Methods In this study, structure-based virtual screening was employed against the active site of BioA to identify new chemical entities for BioA inhibition and top ranking compounds were evaluated for their ability to inhibit BioA enzymatic activity. Results Seven compounds inhibited BioA enzymatic activity by greater than 60% at 100 μg/mL with most potent compounds being A36, A35 and A65, displaying IC50 values of 10.48 μg/mL (28.94 μM), 33.36 μg/mL (88.16 μM) and 39.17 μg/mL (114.42 μM), respectively. Compounds A65 and A35 inhibited Mycobacterium tuberculosis (M. tuberculosis) growth with MIC90 of 20 μg/mL and 80 μg/mL, respectively, whereas compound A36 exhibited relatively weak inhibition of M. tuberculosis growth (83% inhibition at 200 μg/mL). Compound A65 emerged as the most potent compound identified in our study that inhibited BioA enzymatic activity and growth of the pathogen and possessed drug-like properties. Conclusion Our study has identified a few hit molecules against M. tuberculosis BioA that can act as potential candidates for further development of potent anti-tubercular therapeutic agents. PMID:29750019
A User-Centric Knowledge Creation Model in a Web of Object-Enabled Internet of Things Environment
Kibria, Muhammad Golam; Fattah, Sheik Mohammad Mostakim; Jeong, Kwanghyeon; Chong, Ilyoung; Jeong, Youn-Kwae
2015-01-01
User-centric service features in a Web of Object-enabled Internet of Things environment can be provided by using a semantic ontology that classifies and integrates objects on the World Wide Web as well as shares and merges context-aware information and accumulated knowledge. The semantic ontology is applied on a Web of Object platform to virtualize the real world physical devices and information to form virtual objects that represent the features and capabilities of devices in the virtual world. Detailed information and functionalities of multiple virtual objects are combined with service rules to form composite virtual objects that offer context-aware knowledge-based services, where context awareness plays an important role in enabling automatic modification of the system to reconfigure the services based on the context. Converting the raw data into meaningful information and connecting the information to form the knowledge and storing and reusing the objects in the knowledge base can both be expressed by semantic ontology. In this paper, a knowledge creation model that synchronizes a service logistic model and a virtual world knowledge model on a Web of Object platform has been proposed. To realize the context-aware knowledge-based service creation and execution, a conceptual semantic ontology model has been developed and a prototype has been implemented for a use case scenario of emergency service. PMID:26393609
A User-Centric Knowledge Creation Model in a Web of Object-Enabled Internet of Things Environment
Directory of Open Access Journals (Sweden)
Muhammad Golam Kibria
2015-09-01
Full Text Available User-centric service features in a Web of Object-enabled Internet of Things environment can be provided by using a semantic ontology that classifies and integrates objects on the World Wide Web as well as shares and merges context-aware information and accumulated knowledge. The semantic ontology is applied on a Web of Object platform to virtualize the real world physical devices and information to form virtual objects that represent the features and capabilities of devices in the virtual world. Detailed information and functionalities of multiple virtual objects are combined with service rules to form composite virtual objects that offer context-aware knowledge-based services, where context awareness plays an important role in enabling automatic modification of the system to reconfigure the services based on the context. Converting the raw data into meaningful information and connecting the information to form the knowledge and storing and reusing the objects in the knowledge base can both be expressed by semantic ontology. In this paper, a knowledge creation model that synchronizes a service logistic model and a virtual world knowledge model on a Web of Object platform has been proposed. To realize the context-aware knowledge-based service creation and execution, a conceptual semantic ontology model has been developed and a prototype has been implemented for a use case scenario of emergency service.
A User-Centric Knowledge Creation Model in a Web of Object-Enabled Internet of Things Environment.
Kibria, Muhammad Golam; Fattah, Sheik Mohammad Mostakim; Jeong, Kwanghyeon; Chong, Ilyoung; Jeong, Youn-Kwae
2015-09-18
User-centric service features in a Web of Object-enabled Internet of Things environment can be provided by using a semantic ontology that classifies and integrates objects on the World Wide Web as well as shares and merges context-aware information and accumulated knowledge. The semantic ontology is applied on a Web of Object platform to virtualize the real world physical devices and information to form virtual objects that represent the features and capabilities of devices in the virtual world. Detailed information and functionalities of multiple virtual objects are combined with service rules to form composite virtual objects that offer context-aware knowledge-based services, where context awareness plays an important role in enabling automatic modification of the system to reconfigure the services based on the context. Converting the raw data into meaningful information and connecting the information to form the knowledge and storing and reusing the objects in the knowledge base can both be expressed by semantic ontology. In this paper, a knowledge creation model that synchronizes a service logistic model and a virtual world knowledge model on a Web of Object platform has been proposed. To realize the context-aware knowledge-based service creation and execution, a conceptual semantic ontology model has been developed and a prototype has been implemented for a use case scenario of emergency service.
Virtual reality interventions for rehabilitation: considerations for developing protocols.
Boechler, Patricia; Krol, Andrea; Raso, Jim; Blois, Terry
2009-01-01
This paper is a preliminary report on a work in progress that explores the existence of practice effects in early use of virtual reality environments for rehabilitation purposes and the effects of increases in level of difficulty as defined by rate of on-screen objects.
Hirarchical emotion calculation model for virtual human modellin - biomed 2010.
Zhao, Yue; Wright, David
2010-01-01
This paper introduces a new emotion generation method for virtual human modelling. The method includes a novel hierarchical emotion structure, a group of emotion calculation equations and a simple heuristics decision making mechanism, which enables virtual humans to perform emotionally in real-time according to their internal and external factors. Emotion calculation equations used in this research were derived from psychologic emotion measurements. Virtual humans can utilise the information in virtual memory and emotion calculation equations to generate their own numerical emotion states within the hierarchical emotion structure. Those emotion states are important internal references for virtual humans to adopt appropriate behaviours and also key cues for their decision making. A simple heuristics theory is introduced and integrated into decision making process in order to make the virtual humans decision making more like a real human. A data interface which connects the emotion calculation and the decision making structure together has also been designed and simulated to test the method in Virtools environment.
de Boer, I R; Wesselink, P R; Vervoorn, J M
2013-11-01
To describe the development and opportunities for implementation of virtual teeth with and without pathology for use in a virtual learning environment in dental education. The creation of virtual teeth begins by scanning a tooth with a cone beam CT. The resulting scan consists of multiple two-dimensional grey-scale images. The specially designed software program ColorMapEditor connects these two-dimensional images to create a three-dimensional tooth. With this software, any aspect of the tooth can be modified, including its colour, volume, shape and density, resulting in the creation of virtual teeth of any type. This article provides examples of realistic virtual teeth with and without pathology that can be used for dental education. ColorMapEditor offers infinite possibilities to adjust and add options for the optimisation of virtual teeth. Virtual teeth have unlimited availability for dental students, allowing them to practise as often as required. Virtual teeth can be made and adjusted to any shape with any type of pathology. Further developments in software and hardware technology are necessary to refine the ability to colour and shape the interior of the pulp chamber and surface of the tooth to enable not only treatment but also diagnostics and thus create a greater degree of realism. The creation and use of virtual teeth in dental education appears to be feasible but is still in development; it offers many opportunities for the creation of teeth with various pathologies, although an evaluation of its use in dental education is still required. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
A System for Multimodal Interaction with Kinect-Enabled Virtual Windows
Directory of Open Access Journals (Sweden)
Ana M. Bernardos
2015-11-01
Full Text Available Commercial off-the-shelf gaming devices (e.g. such as Kinect are demonstrating to have a great potential beyond their initial service purpose. In particular, when integrated within the environment or as part of smart objects, peripheral COTS for gaming may facilitate the definition of novel interaction methods, particularly applicable to smart spaces service concepts. In this direction, this paper describes a system prototype that makes possible to deliver multimodal interaction with the media contents in a Virtual Window. Using a Kinect device, the Interactive Window itself adjusts the video clipping to the real time perspective of the user – who can freely move within the sensor coverage are. On the clipped video, the user is able to select objects by pointing at meaningful image sections and to initiate actions related to them. Voice orders may also complete the interaction when necessary. Although implemented for smart spaces, the service concept can also be applied to learning, remote control processes or teleconference.
Grasping trajectories in a virtual environment adhere to Weber's law.
Ozana, Aviad; Berman, Sigal; Ganel, Tzvi
2018-06-01
Virtual-reality and telerobotic devices simulate local motor control of virtual objects within computerized environments. Here, we explored grasping kinematics within a virtual environment and tested whether, as in normal 3D grasping, trajectories in the virtual environment are performed analytically, violating Weber's law with respect to object's size. Participants were asked to grasp a series of 2D objects using a haptic system, which projected their movements to a virtual space presented on a computer screen. The apparatus also provided object-specific haptic information upon "touching" the edges of the virtual targets. The results showed that grasping movements performed within the virtual environment did not produce the typical analytical trajectory pattern obtained during 3D grasping. Unlike as in 3D grasping, grasping trajectories in the virtual environment adhered to Weber's law, which indicates relative resolution in size processing. In addition, the trajectory patterns differed from typical trajectories obtained during 3D grasping, with longer times to complete the movement, and with maximum grip apertures appearing relatively early in the movement. The results suggest that grasping movements within a virtual environment could differ from those performed in real space, and are subjected to irrelevant effects of perceptual information. Such atypical pattern of visuomotor control may be mediated by the lack of complete transparency between the interface and the virtual environment in terms of the provided visual and haptic feedback. Possible implications of the findings to movement control within robotic and virtual environments are further discussed.
Hsp90 inhibitors, part 1: definition of 3-D QSAutogrid/R models as a tool for virtual screening.
Ballante, Flavio; Caroli, Antonia; Wickersham, Richard B; Ragno, Rino
2014-03-24
The multichaperone heat shock protein (Hsp) 90 complex mediates the maturation and stability of a variety of oncogenic signaling proteins. For this reason, Hsp90 has emerged as a promising target for anticancer drug development. Herein, we describe a complete computational procedure for building several 3-D QSAR models used as a ligand-based (LB) component of a comprehensive ligand-based (LB) and structure-based (SB) virtual screening (VS) protocol to identify novel molecular scaffolds of Hsp90 inhibitors. By the application of the 3-D QSAutogrid/R method, eight SB PLS 3-D QSAR models were generated, leading to a final multiprobe (MP) 3-D QSAR pharmacophoric model capable of recognizing the most significant chemical features for Hsp90 inhibition. Both the monoprobe and multiprobe models were optimized, cross-validated, and tested against an external test set. The obtained statistical results confirmed the models as robust and predictive to be used in a subsequent VS.
Miloeski, Aleksandar
2017-01-01
The aim of this thesis is to create a functional application for the Android environment that allows the user to do simple virtual drawings without the use of the touch screen, but rather through hand motions caught by the camera. There is a variety of approaches to this end, which vary by complexity and performance. This piece of work attempts to find a middle ground among the existing algorithms, as well as to build on and improve them specifically for this particular task. The idea is ...
Blanco, Bego; Taboada, Ianire; Fajardo, Jose Oscar; Liberal, Fidel
2017-01-01
In the context of cloud-enabled 5G radio access networks with network function virtualization capabilities, we focus on the virtual network function placement problem for a multitenant cluster of small cells that provide mobile edge computing services. Under an emerging distributed network architecture and hardware infrastructure, we employ cloud-enabled small cells that integrate microservers for virtualization execution, equipped with additional hardware appliances. We develop an energy-awa...
Chakraborty, Sandipan; Ramachandran, Balaji; Basu, Soumalee
2014-10-01
Mimicking receptor flexibility during receptor-ligand binding is a challenging task in computational drug design since it is associated with a large increase in the conformational search space. In the present study, we have devised an in silico design strategy incorporating receptor flexibility in virtual screening to identify potential lead compounds as inhibitors for flexible proteins. We have considered BACE1 (β-secretase), a key target protease from a therapeutic perspective for Alzheimer's disease, as the highly flexible receptor. The protein undergoes significant conformational transitions from open to closed form upon ligand binding, which makes it a difficult target for inhibitor design. We have designed a hybrid structure-activity model containing both ligand based descriptors and energetic descriptors obtained from molecular docking based on a dataset of structurally diverse BACE1 inhibitors. An ensemble of receptor conformations have been used in the docking study, further improving the prediction ability of the model. The designed model that shows significant prediction ability judged by several statistical parameters has been used to screen an in house developed 3-D structural library of 731 phytochemicals. 24 highly potent, novel BACE1 inhibitors with predicted activity (Ki) ≤ 50 nM have been identified. Detailed analysis reveals pharmacophoric features of these novel inhibitors required to inhibit BACE1.
Virtual Training of the Myosignal.
Directory of Open Access Journals (Sweden)
Bernhard Terlaak
Full Text Available To investigate which of three virtual training methods produces the largest learning effects on discrete and continuous myocontrol. The secondary objective was to examine the relation between myocontrol and manual motor control tests.A cohort analytic study.University laboratory.3 groups of 12 able-bodied participants (N = 36.Participants trained the control over their myosignals on 3 consecutive days. Training was done with either myosignal feedback on a computer screen, a virtual myoelectric prosthetic hand or a computer game. Participants performed 2 myocontrol tests and 2 manual motor control tests before the first and after the last training session. They were asked to open and close a virtual prosthetic hand on 3 different velocities as a discrete myocontrol test and followed a line with their myosignals for 30 seconds as a continuous myocontrol test. The motor control tests were a pegboard and grip-force test.Discrete myocontrol test: mean velocities. Continuous myocontrol test: error and error SD. Pegboard test: time to complete. Grip-force test: produced forces.No differences in learning effects on myocontrol were found for the different virtual training methods. Discrete myocontrol ability did not significantly improve as a result of training. Continuous myocontrol ability improved significantly as a result of training, both on average control and variability. All correlations between the motor control and myocontrol test outcome measures were below .50.Three different virtual training methods showed comparable results when learning myocontrol. Continuous myocontrol was improved by training while discrete myocontrol was not. Myocontrol ability could not be predicted by the manual motor control tests.
A virtual laboratory for medical image analysis
Olabarriaga, Sílvia D.; Glatard, Tristan; de Boer, Piter T.
2010-01-01
This paper presents the design, implementation, and usage of a virtual laboratory for medical image analysis. It is fully based on the Dutch grid, which is part of the Enabling Grids for E-sciencE (EGEE) production infrastructure and driven by the gLite middleware. The adopted service-oriented
Merka, J.; Dolan, C. F.
2015-12-01
Finding and retrieving space physics data is often a complicated taskeven for publicly available data sets: Thousands of relativelysmall and many large data sets are stored in various formats and, inthe better case, accompanied by at least some documentation. VirtualHeliospheric and Magnetospheric Observatories (VHO and VMO) help researches by creating a single point of uniformdiscovery, access, and use of heliospheric (VHO) and magnetospheric(VMO) data.The VMO and VHO functionality relies on metadata expressed using theSPASE data model. This data model is developed by the SPASE WorkingGroup which is currently the only international group supporting globaldata management for Solar and Space Physics. The two Virtual Observatories(VxOs) have initiated and lead a development of a SPASE-related standardnamed SPASE Query Language for provided a standard way of submittingqueries and receiving results.The VMO and VHO use SPASE and SPASEQL for searches based on various criteria such as, for example, spatial location, time of observation, measurement type, parameter values, etc. The parameter values are represented by their statisticalestimators calculated typically over 10-minute intervals: mean, median, standard deviation, minimum, and maximum. The use of statistical estimatorsenables science driven data queries that simplify and shorten the effort tofind where and/or how often the sought phenomenon is observed, as we will present.
Sanhueza, Carlos A; Cartmell, Jonathan; El-Hawiet, Amr; Szpacenko, Adam; Kitova, Elena N; Daneshfar, Rambod; Klassen, John S; Lang, Dean E; Eugenio, Luiz; Ng, Kenneth K-S; Kitov, Pavel I; Bundle, David R
2015-01-07
A focused library of virtual heterobifunctional ligands was generated in silico and a set of ligands with recombined fragments was synthesized and evaluated for binding to Clostridium difficile toxins. The position of the trisaccharide fragment was used as a reference for filtering docked poses during virtual screening to match the trisaccharide ligand in a crystal structure. The peptoid, a diversity fragment probing the protein surface area adjacent to a known binding site, was generated by a multi-component Ugi reaction. Our approach combines modular fragment-based design with in silico screening of synthetically feasible compounds and lays the groundwork for future efforts in development of composite bifunctional ligands for large clostridial toxins.
Virtual reality applied to teletesting
van den Berg, Thomas J.; Smeenk, Roland J. M.; Mazy, Alain; Jacques, Patrick; Arguello, Luis; Mills, Simon
2003-05-01
The activity "Virtual Reality applied to Teletesting" is related to a wider European Space Agency (ESA) initiative of cost reduction, in particular the reduction of test costs. Reduction of costs of space related projects have to be performed on test centre operating costs and customer company costs. This can accomplished by increasing the automation and remote testing ("teletesting") capabilities of the test centre. Main problems related to teletesting are a lack of situational awareness and the separation of control over the test environment. The objective of the activity is to evaluate the use of distributed computing and Virtual Reality technology to support the teletesting of a payload under vacuum conditions, and to provide a unified man-machine interface for the monitoring and control of payload, vacuum chamber and robotics equipment. The activity includes the development and testing of a "Virtual Reality Teletesting System" (VRTS). The VRTS is deployed at one of the ESA certified test centres to perform an evaluation and test campaign using a real payload. The VRTS is entirely written in the Java programming language, using the J2EE application model. The Graphical User Interface runs as an applet in a Web browser, enabling easy access from virtually any place.
Building virtual pentesting labs for advanced penetration testing
Cardwell, Kevin
2014-01-01
Written in an easy-to-follow approach using hands-on examples, this book helps you create virtual environments for advanced penetration testing, enabling you to build a multi-layered architecture to include firewalls, IDS/IPS, web application firewalls, and endpoint protection, which is essential in the penetration testing world. If you are a penetration tester, security consultant, security test engineer, or analyst who wants to practice and perfect penetration testing skills by building virtual pen testing labs in varying industry scenarios, this is the book for you. This book is ideal if yo
Resilient Multi-Domain Command and Control: Enabling Solutions for 2025 with Virtual Reality
2017-04-16
could be played from the direction of the physical location of an internet protocol router that is under cyber- attack. The attack doesn’t actually...These systems give one a window into a virtual world that is independent of other users in the physical space. Where individuals at a local site...picture for a particular site or in an austere environment using a tablet or smartphone platform. Coupled with appropriate communications equipment
Combinatorial Pharmacophore-Based 3D-QSAR Analysis and Virtual Screening of FGFR1 Inhibitors
Directory of Open Access Journals (Sweden)
Nannan Zhou
2015-06-01
Full Text Available The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR signaling pathway plays crucial roles in cell proliferation, angiogenesis, migration, and survival. Aberration in FGFRs correlates with several malignancies and disorders. FGFRs have proved to be attractive targets for therapeutic intervention in cancer, and it is of high interest to find FGFR inhibitors with novel scaffolds. In this study, a combinatorial three-dimensional quantitative structure-activity relationship (3D-QSAR model was developed based on previously reported FGFR1 inhibitors with diverse structural skeletons. This model was evaluated for its prediction performance on a diverse test set containing 232 FGFR inhibitors, and it yielded a SD value of 0.75 pIC50 units from measured inhibition affinities and a Pearson’s correlation coefficient R2 of 0.53. This result suggests that the combinatorial 3D-QSAR model could be used to search for new FGFR1 hit structures and predict their potential activity. To further evaluate the performance of the model, a decoy set validation was used to measure the efficiency of the model by calculating EF (enrichment factor. Based on the combinatorial pharmacophore model, a virtual screening against SPECS database was performed. Nineteen novel active compounds were successfully identified, which provide new chemical starting points for further structural optimization of FGFR1 inhibitors.
Directory of Open Access Journals (Sweden)
Negut, A.
2014-07-01
Full Text Available Virtual reality scenarios have been developed in order to assess cognitive functioning such as: memory, attention and executive function. Most scenarios replicate everyday situations like shopping activities, navigation through a park or a street, learning objects in an apartment or virtual office, or sitting and solving tasks in a classroom or apartment. Results of these studies support the use of virtual reality scenarios in neurocognitive assessment. Virtual scenarios that are used in cognitive training include a wide range of contexts from everyday life such as: a store, a kitchen, a city, as well as exercises like touching a ball on a screen for movement coordination, collecting a coconut and positioning it in a basket. Overall, virtual reality-based assessment or rehabilitation tools seem to be valid, reliable and efficient with an increased level of ecological validity.
Virtual reality in simulation of operational procedures in radioactive waste deposits
International Nuclear Information System (INIS)
Freitas, Victor Goncalves Gloria
2016-01-01
One of the biggest problems in the nuclear area are still the radioactive waste generated in the various applications of this form of energy, all these tailings are stored in warehouses that often are monitored and restructured for better allocation of then. These tailings are stored until it is safe to release into the environment. This work presents a methodology based on virtual reality, for the development of virtual deposits of radioactive waste in order to enable virtual simulations in these deposits. As application will be developed virtually the nuclear waste repository located at the Institute of Nuclear Engineering IEN/CNEN. The development of a virtual warehouse, more specifically, makes it possible to simulate/train the allocation and reallocation of materials with low and medium level of radioactivity, seen the possibility of locomotion of virtual objects and dynamic calculation of the rate of radiation in this environment. Using this methodology it also possible know the accumulated dose, by the virtual character, during the procedures run in the virtual environment. (author)
Virtual Screening for Potential Inhibitors of NS3 Protein of Zika Virus
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Maheswata Sahoo
2016-09-01
Full Text Available Zika virus (ZIKV is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3 protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of –5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H-one was found to interact with NS3 protein with binding energy of –7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.
Virtually teaching virtual leadership
DEFF Research Database (Denmark)
Henriksen, Thomas Duus; Nielsen, Rikke Kristine; Børgesen, Kenneth
2017-01-01
This paper seeks to investigate the challenges to virtual collaboration and leadership on basis of findings from a virtual course on collaboration and leadership. The course used for this experiment was designed as a practical approach, which allowed participants to experience curriculum phenomena....... This experimental course provided insights into the challenges involved in virtual processes, and those experiences where used for addressing the challenges that virtual leadership is confronted with. Emphasis was placed on the reduction of undesired virtual distance and its consequences through affinity building....... We found that student scepticism appeared when a breakdown resulted in increasing virtual distance, and raises questions on how leaders might translate or upgrade their understandings of leadership to handling such increased distance through affinity building....
Directory of Open Access Journals (Sweden)
Tarali Chowdhury
2014-03-01
Full Text Available With the emergence of multi-drug resistant pathogens at alarming frequency, there has been an increase interest in the development of novel drugs from natural resources. The use of higher plants and preparations made from them to treat infections is a longstanding practice in a large part of the population, especially in the developing countries, where there is dependence on traditional medicine for a variety of ailments. The virtual screening method was used in this study to analyze the docking and inhibitory activities of some natural bioactive compounds present within Garcinia pedunculata against hemolysin toxin of Staphylococcus aureus, gamma-hemolysin component A hlgA. The study resulted in identifying compounds 1,3,6,7-tetrahydroxy-xanthone and garcinone D with high binding affinity towards the target protein revealing them as potent inhibitors that could be further used to create new drug source in the treatment of staphyloccocal infections.
Energy Technology Data Exchange (ETDEWEB)
Augusto, Silas C.; Mol, Antonio C.A.; Mol, Pedro C.; Sales, Douglas S. [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil)], e-mail: silas@ien.gov.br, e-mail: mol@ien.gov.br, e-mail: pedro98@gmail.com, e-mail: dsales@ien.gov.br
2009-07-01
The physical security of facilities containing radioactive objects, an already important matter, now has a new aggravating factor: the existence of groups intending to obtain radioactive materials for the purpose of intentionally induce radioactive contamination incidents, as for example the explosion of dirty bombs in populated regions, damaging both people and environment. In this context, the physical security of such facilities must be reinforced so to reduce the possibilities of such incidents. This paper presents a adapted game engine used as a virtual reality system, enabling the modeling and simulation of scenarios of nuclear facilities containing radioactive objects. In these scenarios, the physical protection barriers, as fences and walls, are simulated along with vigilance screens. Using a computer network, several users can participate simultaneously in the simulation, being represented by avatars. Users can play the roles of both invaders and security staff. The invaders have as objective to surpass the facility's physical protection barriers to steal radioactive objects and flee. The security staff have as objective to prevent and stop the theft of radioactive objects from the facility. The system can be used to analysis simulated scenarios and train vigilance/security staff. A test scenario was already developed and used, and the preliminary tests had satisfactory results, as they enabled the evaluation of the physical protection barriers of the virtual facility, and the training of those who participated in the simulations in the functions of a security staff. (author)
International Nuclear Information System (INIS)
Augusto, Silas C.; Mol, Antonio C.A.; Mol, Pedro C.; Sales, Douglas S.
2009-01-01
The physical security of facilities containing radioactive objects, an already important matter, now has a new aggravating factor: the existence of groups intending to obtain radioactive materials for the purpose of intentionally induce radioactive contamination incidents, as for example the explosion of dirty bombs in populated regions, damaging both people and environment. In this context, the physical security of such facilities must be reinforced so to reduce the possibilities of such incidents. This paper presents a adapted game engine used as a virtual reality system, enabling the modeling and simulation of scenarios of nuclear facilities containing radioactive objects. In these scenarios, the physical protection barriers, as fences and walls, are simulated along with vigilance screens. Using a computer network, several users can participate simultaneously in the simulation, being represented by avatars. Users can play the roles of both invaders and security staff. The invaders have as objective to surpass the facility's physical protection barriers to steal radioactive objects and flee. The security staff have as objective to prevent and stop the theft of radioactive objects from the facility. The system can be used to analysis simulated scenarios and train vigilance/security staff. A test scenario was already developed and used, and the preliminary tests had satisfactory results, as they enabled the evaluation of the physical protection barriers of the virtual facility, and the training of those who participated in the simulations in the functions of a security staff. (author)
Differences in spatial understanding between physical and virtual models
Directory of Open Access Journals (Sweden)
Lei Sun
2014-03-01
Full Text Available In the digital age, physical models are still used as major tools in architectural and urban design processes. The reason why designers still use physical models remains unclear. In addition, physical and 3D virtual models have yet to be differentiated. The answers to these questions are too complex to account for in all aspects. Thus, this study only focuses on the differences in spatial understanding between physical and virtual models. In particular, it emphasizes on the perception of scale. For our experiment, respondents were shown a physical model and a virtual model consecutively. A questionnaire was then used to ask the respondents to evaluate these models objectively and to establish which model was more accurate in conveying object size. Compared with the virtual model, the physical model tended to enable quicker and more accurate comparisons of building heights.
Li, Liwei; Khanna, May; Jo, Inha; Wang, Fang; Ashpole, Nicole M; Hudmon, Andy; Meroueh, Samy O
2011-04-25
We assess the performance of our previously reported structure-based support vector machine target-specific scoring function across 41 targets, 40 among them from the Directory of Useful Decoys (DUD). The area under the curve of receiver operating characteristic plots (ROC-AUC) revealed that scoring with SVM-SP resulted in consistently better enrichment over all target families, outperforming Glide and other scoring functions, most notably among kinases. In addition, SVM-SP performance showed little variation among protein classes, exhibited excellent performance in a test case using a homology model, and in some cases showed high enrichment even with few structures used to train a model. We put SVM-SP to the test by virtual screening 1125 compounds against two kinases, EGFR and CaMKII. Among the top 25 EGFR compounds, three compounds (1-3) inhibited kinase activity in vitro with IC₅₀ of 58, 2, and 10 μM. In cell cultures, compounds 1-3 inhibited nonsmall cell lung carcinoma (H1299) cancer cell proliferation with similar IC₅₀ values for compound 3. For CaMKII, one compound inhibited kinase activity in a dose-dependent manner among 20 tested with an IC₅₀ of 48 μM. These results are encouraging given that our in-house library consists of compounds that emerged from virtual screening of other targets with pockets that are different from typical ATP binding sites found in kinases. In light of the importance of kinases in chemical biology, these findings could have implications in future efforts to identify chemical probes of kinases within the human kinome.
Marrero-Ponce, Yovani; Iyarreta-Veitía, Maité; Montero-Torres, Alina; Romero-Zaldivar, Carlos; Brandt, Carlos A; Avila, Priscilla E; Kirchgatter, Karin; Machado, Yanetsy
2005-01-01
Malaria has been one of the most significant public health problems for centuries. It affects many tropical and subtropical regions of the world. The increasing resistance of Plasmodium spp. to existing therapies has heightened alarms about malaria in the international health community. Nowadays, there is a pressing need for identifying and developing new drug-based antimalarial therapies. In an effort to overcome this problem, the main purpose of this study is to develop simple linear discriminant-based quantitative structure-activity relationship (QSAR) models for the classification and prediction of antimalarial activity using some of the TOMOCOMD-CARDD (TOpological MOlecular COMputer Design-Computer Aided "Rational" Drug Design) fingerprints, so as to enable computational screening from virtual combinatorial datasets. In this sense, a database of 1562 organic chemicals having great structural variability, 597 of them antimalarial agents and 965 compounds having other clinical uses, was analyzed and presented as a helpful tool, not only for theoretical chemists but also for other researchers in this area. This series of compounds was processed by a k-means cluster analysis in order to design training and predicting sets. Afterward, two linear classification functions were derived in order to discriminate between antimalarial and nonantimalarial compounds. The models (including nonstochastic and stochastic indices) correctly classify more than 93% of the compound set, in both training and external prediction datasets. They showed high Matthews' correlation coefficients, 0.889 and 0.866 for the training set and 0.855 and 0.857 for the test one. The models' predictivity was also assessed and validated by the random removal of 10% of the compounds to form a new test set, for which predictions were made using the models. The overall means of the correct classification for this process (leave group 10% full-out cross validation) using the equations with nonstochastic
Writing virtual environments for software visualization
Jeffery, Clinton
2015-01-01
This book describes the software for creating networked, 3D multi-user virtual environments that allow users to create and remotely share visualizations of program behavior. The authors cover the major features of collaborative virtual environments and how to program them in a very high level language, and show how visualization can enable important advances in our ability to understand and reduce the costs of maintaining software. The book also examines the application of popular game-like software technologies. • Discusses the acquisition of program behavior data to be visualized • Demonstrates the integration of multiple 2D and 3D dynamic views within a 3Dscene • Presents the network messaging capabilities to share those visualizations
Ferreira, P G; Ferraz, A C; Figueiredo, J E; Lima, C F; Rodrigues, V G; Taranto, A G; Ferreira, J M S; Brandão, G C; Vieira-Filho, S A; Duarte, L P; de Brito Magalhães, C L; de Magalhães, J C
2018-02-24
Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC 50 ) of 0.247 μmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC 50 ) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.
Developing a Virtual Network of Research Observatories
Hooper, R. P.; Kirschtl, D.
2008-12-01
The hydrologic community has been discussing the concept of a network of observatories for the advancement of hydrologic science in areas of scaling processes, in testing generality of hypotheses, and in examining non-linear couplings between hydrologic, biotic, and human systems. The Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) is exploring the formation of a virtual network of observatories, formed from existing field studies without regard to funding source. Such a network would encourage sharing of data, metadata, field methods, and data analysis techniques to enable multidisciplinary synthesis, meta-analysis, and scientific collaboration in hydrologic and environmental science and engineering. The virtual network would strive to provide both the data and the environmental context of the data through advanced cyberinfrastructure support. The foundation for this virtual network is Water Data Services that enable the publication of time-series data collected at fixed points using a services-oriented architecture. These publication services, developed in the CUAHSI Hydrologic Information Systems project, permit the discovery of data from both academic and government sources through a single portal. Additional services under consideration are publication of geospatial data sets, immersive environments based upon site digital elevation models, and a common web portal to member sites populated with structured data about the site (such as land use history and geologic setting) to permit understanding the environmental context of the data being shared.
Virtualization of work in global supply chains
Directory of Open Access Journals (Sweden)
Sabina Wyrwich-Płotka
2016-12-01
Full Text Available Background: The paper is devoted to the notion and benefits of implementing virtual work in global supply chains. Virtual work must be understood as an intentional activity of a human being, aimed at rendering services (tangible and intangible, by means of ITC tools, performed in a distance from the traditional place of work, in a mobile manner. The empirical research were conducted on the basis of 4 case studies of global leaders of supply chains, which in accordance with M. Fisher's classification, represent two types. The case studies confirmed the positive influence of virtual work both in effective and flexible supply chains. Favourable market and technological conditions and increasing awareness of benefits of virtual work will make it more and more widespread in companies comprising global supply chains. The aim of the study is to demonstrate the cause and effect relationships between virtual work and competitiveness of efficient and flexible supply chain. Methods: The paper is based on the available recent scientific-theoretical research and publication. The authors analyzed 4 enterprises in Poland. The enterprises representing a flexible or an effective supply chain, either using or not a virtual work. The study carried out the authors had the form of individual interviews. The authors used case studies to show that virtual work brings notable benefits in an effective and flexible supply chain. Results: Based on these case studies, the authors demonstrated reasons to implement virtual work in selected enterprises. The reasons to implement virtual work are determinants of possible achieve economies in effective and flexible supply chain Conclusions: The examined case studies show that virtual work brings different benefits. In the effective supply chain, virtual workers enable to increase effectiveness and financial results for example. In the flexible supply chain the virtual work can be a way to maintain and build long
Raising Virtual Laboratories in Australia onto global platforms
Wyborn, L. A.; Barker, M.; Fraser, R.; Evans, B. J. K.; Moloney, G.; Proctor, R.; Moise, A. F.; Hamish, H.
2016-12-01
Across the globe, Virtual Laboratories (VLs), Science Gateways (SGs), and Virtual Research Environments (VREs) are being developed that enable users who are not co-located to actively work together at various scales to share data, models, tools, software, workflows, best practices, etc. Outcomes range from enabling `long tail' researchers to more easily access specific data collections, to facilitating complex workflows on powerful supercomputers. In Australia, government funding has facilitated the development of a range of VLs through the National eResearch Collaborative Tools and Resources (NeCTAR) program. The VLs provide highly collaborative, research-domain oriented, integrated software infrastructures that meet user community needs. Twelve VLs have been funded since 2012, including the Virtual Geophysics Laboratory (VGL); Virtual Hazards, Impact and Risk Laboratory (VHIRL); Climate and Weather Science Laboratory (CWSLab); Marine Virtual Laboratory (MarVL); and Biodiversity and Climate Change Virtual Laboratory (BCCVL). These VLs share similar technical challenges, with common issues emerging on integration of tools, applications and access data collections via both cloud-based environments and other distributed resources. While each VL began with a focus on a specific research domain, communities of practice have now formed across the VLs around common issues, and facilitate identification of best practice case studies, and new standards. As a result, tools are now being shared where the VLs access data via data services using international standards such as ISO, OGC, W3C. The sharing of these approaches is starting to facilitate re-usability of infrastructure and is a step towards supporting interdisciplinary research. Whilst the focus of the VLs are Australia-centric, by using standards, these environments are able to be extended to analysis on other international datasets. Many VL datasets are subsets of global datasets and so extension to global is a
Development and Evaluation of the Virtual Prototype of the First Saudi Arabian-Designed Car
Directory of Open Access Journals (Sweden)
Mustufa H. Abidi
2016-10-01
Full Text Available Prototyping and evaluation are imperative phases of the present product design and development process. Although digital modeling and analysis methods are widely employed at various product development stages, still, building a physical prototype makes the present typical process expensive and time consuming. Therefore, it is necessary to implement new technologies, such as virtual prototyping, which can enable industry to have a rapid and more controlled decision making process. Virtual prototyping has come a long way in recent years, where current environments enable stereoscopic visuals, surround sound and ample interaction with the generated models. It is also important to evaluate how representative the developed virtual prototype is when compared to the real-world counterpart and the sense of presence reported by users of the virtual prototype. This paper describes the systematic procedure to develop a virtual prototype of Gazal-1 (i.e., the first car prototype designed by Saudi engineers in a semi-immersive virtual environment. The steps to develop a virtual prototype from CAD (computer-aided design models are explained in detail. Various issues involved in the different phases for the development of the virtual prototype are also discussed comprehensively. The paper further describes the results of the subjective assessment of a developed virtual prototype of a Saudi Arabian-designed automobile. User’s feedback is recorded using a presence questionnaire. Based on the user-based study, it is revealed that the virtual prototype is representative of the real Saudi Arabian car and offers a flexible environment to analyze design features when compared against its physical prototype. The capabilities of the virtual environment are validated with the application of the car prototype. Finally, vital requirements and directions for future research are also presented.
From the Symbolic Analysis of Virtual Faces to a Smiles Machine.
Ochs, Magalie; Diday, Edwin; Afonso, Filipe
2016-02-01
In this paper, we present an application of symbolic data processing for the design of virtual character's smiling facial expressions. A collected database of virtual character's smiles directly created by users has been explored using symbolic data analysis methods. An unsupervised analysis has enabled us to identify the morphological and dynamic characteristics of different types of smiles as well as of combinations of smiles. Based on the symbolic data analysis, to generate different smiling faces, we have developed procedures to automatically reconstitute smiling virtual faces from a point in a multidimensional space corresponding to a principal component analysis plane.
Larsson, Emanuel; Martin, Sabine; Lazzarini, Marcio; Tromba, Giuliana; Missbach-Guentner, Jeannine; Pinkert-Leetsch, Diana; Katschinski, Dörthe M.; Alves, Frauke
2017-01-01
The small size of the adult and developing mouse heart poses a great challenge for imaging in preclinical research. The aim of the study was to establish a phosphotungstic acid (PTA) ex-vivo staining approach that efficiently enhances the x-ray attenuation of soft-tissue to allow high resolution 3D visualization of mouse hearts by synchrotron radiation based μCT (SRμCT) and classical μCT. We demonstrate that SRμCT of PTA stained mouse hearts ex-vivo allows imaging of the cardiac atrium, ventricles, myocardium especially its fibre structure and vessel walls in great detail and furthermore enables the depiction of growth and anatomical changes during distinct developmental stages of hearts in mouse embryos. Our x-ray based virtual histology approach is not limited to SRμCT as it does not require monochromatic and/or coherent x-ray sources and even more importantly can be combined with conventional histological procedures. Furthermore, it permits volumetric measurements as we show for the assessment of the plaque volumes in the aortic valve region of mice from an ApoE-/- mouse model. Subsequent, Masson-Goldner trichrome staining of paraffin sections of PTA stained samples revealed intact collagen and muscle fibres and positive staining of CD31 on endothelial cells by immunohistochemistry illustrates that our approach does not prevent immunochemistry analysis. The feasibility to scan hearts already embedded in paraffin ensured a 100% correlation between virtual cut sections of the CT data sets and histological heart sections of the same sample and may allow in future guiding the cutting process to specific regions of interest. In summary, since our CT based virtual histology approach is a powerful tool for the 3D depiction of morphological alterations in hearts and embryos in high resolution and can be combined with classical histological analysis it may be used in preclinical research to unravel structural alterations of various heart diseases. PMID:28178293
Physics Education in Virtual Reality: An Example
Kaufmann, Hannes; Meyer, Bernd
2009-01-01
We present an immersive virtual reality (VR) application for physics education. It utilizes a recent physics engine developed for the PC gaming market to simulate physical experiments correctly and accurately. Students are enabled to actively build their own experiments and study them. A variety of tools are provided to analyze forces, mass, paths…
Directory of Open Access Journals (Sweden)
Jakub Štogr
2011-04-01
Full Text Available Multiuser virtual environments (MUVEs generate a large amount of data but most of them are not accessible even to users who triggered them. What’s more, most datasets are not even stored for further use; they have only temporary character and very short "halftime of decay" limited f.e. to onesecondlong screen display. Such a huge loss of data makes evaluation of knowledge transfer in MUVEs almost impossible. There is a need to both improve monitoring capabilities of MUVEs to be able to make completion assessment and use MUVEs that enable simulation (reexperience using complete datasets gathered from environment itself. Future research in the field of simulation methodology is suggested.
Directory of Open Access Journals (Sweden)
Renata Rachide Nunes
Full Text Available The main challenge in the control of malaria has been the emergence of drug-resistant parasites. The presence of drug-resistant Plasmodium sp. has raised the need for new antimalarial drugs. Molecular modelling techniques have been used as tools to develop new drugs. In this study, we employed virtual screening of a pyrazol derivative (Tx001 against four malaria targets: plasmepsin-IV, plasmepsin-II, falcipain-II, and PfATP6. The receiver operating characteristic curves and area under the curve (AUC were established for each molecular target. The AUC values obtained for plasmepsin-IV, plasmepsin-II, and falcipain-II were 0.64, 0.92, and 0.94, respectively. All docking simulations were carried out using AutoDock Vina software. The ligand Tx001 exhibited a better interaction with PfATP6 than with the reference compound (-12.2 versus -6.8 Kcal/mol. The Tx001-PfATP6 complex was submitted to molecular dynamics simulations in vacuum implemented on an NAMD program. The ligand Tx001 docked at the same binding site as thapsigargin, which is a natural inhibitor of PfATP6. Compound TX001 was evaluated in vitro with a P. falciparum strain (W2 and a human cell line (WI-26VA4. Tx001 was discovered to be active against P. falciparum (IC50 = 8.2 µM and inactive against WI-26VA4 (IC50 > 200 µM. Further ligand optimisation cycles generated new prospects for docking and biological assays.
A Hierarchy of Needs for a Virtual Class.
Beise, Catherine; Wynekoop, Judy
Distance Learning (DL) initiatives are proceeding full speed ahead, both within traditional universities and in "virtual" institutions specializing in on-line course delivery. Much has been written about the virtues and limitations, the obstacles and enablers, and the "Do's" and "Don'ts" of DL. However, considerable…
Increasing performance in KVM virtualization within a Tier-1 environment
International Nuclear Information System (INIS)
Chierici, Andrea; Salomoni, Davide
2012-01-01
This work shows the optimizations we have been investigating and implementing at the KVM (Kernel-based Virtual Machine) virtualization layer in the INFN Tier-1 at CNAF, based on more than a year of experience in running thousands of virtual machines in a production environment used by several international collaborations. These optimizations increase the adaptability of virtualization solutions to demanding applications like those run in our institute (High-Energy Physics). We will show performance differences among different filesystems (like ext3 vs ext4) when used as KVM host local storage. We will provide guidelines for solid state disks (SSD) adoption, for deployment of SR-IOV (Single Root I/O Virtualization) enabled hardware and what is the best solution to distribute and instantiate read-only virtual machine images. This work has been driven by the project called Worker Nodes on Demand Service (WNoDeS), a framework designed to offer local, grid or cloud-based access to computing and storage resources, preserving maximum compatibility with existing computing center policies and workflows.
Virtual CT-colonoscopy. Examination technique, limitations, and prospects
International Nuclear Information System (INIS)
Springer, P.; Dessl, A.; Giacomuzzi, S.M.; Stoehr, B.; Stoeger, A.; Bodner, G.; Buchberger, W.
1997-01-01
Virtual CT-colonoscopy is a post-processing method which allows for reconstruction of inner bowel surface structures from helical CT datasets. The reconstructed images simulate the views which are known from fiberoptic endoscopy. Since colorectal cancer is the second main cause of death in USA and Europe today and since recent screening recommendations are often ignored by the public, a non-invasive or minimal-invasive procedure for colonic evaluation would offer some benefits. Virtual CT-colonoscopy generally involves three essential steps: patient preparation with cleansing of the bowel and administration of an air enema, helical CT-examination by using appropriate scan parameters, and interactive 3D rendering of the volume dataset. Although recent studies have demonstrated that polypoid lesions of about 5 mm size are well detectable and although virtual colonoscopy offers many advantages over fiberoptic endoscopy, some technical and clinical limitations must still be noted. Thus, the current inability of virtual colonoscopy to provide texture and color leads to problems in identifying flat lesions; the presence of retained or adherent fecal matter may result to false positive diagnosis and collapsed segments of bowel may cause problems as they cannot subsequently be evaluated during image reconstruction. Virtual endoscopy is still in its infancy and further technical and clinical development are necessary. (orig./AJ) [de
A Novel Virtual Node Hexahedral Element with Exact Integration and Octree Meshing
Directory of Open Access Journals (Sweden)
Logah Perumal
2016-01-01
Full Text Available The method presented in this work is a 3-dimensional polyhedral finite element (3D PFEM based on virtual node method. Novel virtual node polyhedral elements (termed as VPHE are developed here, particularly virtual node hexahedral element (termed as VHE. Stiffness matrices of these polyhedral elements consist of simple polynomials. Thus, a new algorithm is introduced in this paper, which enables exact integration of monomials without a need for high number of integration points and weights. The number of nodes for VHE elements is not restricted, as opposed to the conventional hexahedral elements. This feature enables formulation of transition elements (termed as T-VHE which are useful to adaptive computation. Performances of the new VHE elements in solid mechanics and conductive heat transfer phenomena are examined through numerical simulations. The new T-VHE elements are utilized in octree mesh. The VHE elements are found to produce good results and T-VHE elements help to reduce number of global nodes for the analysis.
Towards Gesture-Based Multi-User Interactions in Collaborative Virtual Environments
Pretto, N.; Poiesi, F.
2017-11-01
We present a virtual reality (VR) setup that enables multiple users to participate in collaborative virtual environments and interact via gestures. A collaborative VR session is established through a network of users that is composed of a server and a set of clients. The server manages the communication amongst clients and is created by one of the users. Each user's VR setup consists of a Head Mounted Display (HMD) for immersive visualisation, a hand tracking system to interact with virtual objects and a single-hand joypad to move in the virtual environment. We use Google Cardboard as a HMD for the VR experience and a Leap Motion for hand tracking, thus making our solution low cost. We evaluate our VR setup though a forensics use case, where real-world objects pertaining to a simulated crime scene are included in a VR environment, acquired using a smartphone-based 3D reconstruction pipeline. Users can interact using virtual gesture-based tools such as pointers and rulers.
Haptic Systems for Post-Stroke Rehabilitation: from Virtual Reality to Remote Rehabilitation
Daud, Omar Andres
2011-01-01
Haptic devices are becoming a common and significant tool in the perspective of robotic neurorehabilitation for motor learning, particularly in post-stroke patients. As a standard approach, this kind of devices are used in a local environment, where the patient interacts with a virtual environment recreated in the computer's screen. In this sense, a general framework for virtual reality based rehabilitation was developed. All the features of the framework, such as the control loop and the ext...
Small Screen Use and Driving Safety.
Atchley, Paul; Strayer, David L
2017-11-01
The increased availability of "small screens," wireless devices with Internet-enabled connections, and their associated applications has almost overnight changed the way that we interact with our phones. The current work outlines some of the aspects of this problem as it relates to the influence of small screens on driving safety. Small screens are highly compelling to drivers, both for the information they convey and because the ability to ignore them while driving is impaired by cognitive resources used by the driving task itself. However, much is unknown about why people make choices to multitask while driving. Given the safety risks, it is recommended that parents, the public, and regulators take a stand against the use of Internet-enabled small screens unrelated to driving when the vehicle is in motion. Copyright © 2017 by the American Academy of Pediatrics.
Reverse screening methods to search for the protein targets of chemopreventive compounds
Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan
2018-05-01
This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and
Therrien, Eric; Weill, Nathanael; Tomberg, Anna; Corbeil, Christopher R; Lee, Devin; Moitessier, Nicolas
2014-11-24
The use of predictive computational methods in the drug discovery process is in a state of continual growth. Over the last two decades, an increasingly large number of docking tools have been developed to identify hits or optimize lead molecules through in-silico screening of chemical libraries to proteins. In recent years, the focus has been on implementing protein flexibility and water molecules. Our efforts led to the development of Fitted first reported in 2007 and further developed since then. In this study, we wished to evaluate the impact of protein flexibility and occurrence of water molecules on the accuracy of the Fitted docking program to discriminate active compounds from inactive compounds in virtual screening (VS) campaigns. For this purpose, a total of 171 proteins cocrystallized with small molecules representing 40 unique enzymes and receptors as well as sets of known ligands and decoys were selected from the Protein Data Bank (PDB) and the Directory of Useful Decoys (DUD), respectively. This study revealed that implementing displaceable crystallographic or computationally placed particle water molecules and protein flexibility can improve the enrichment in active compounds. In addition, an informed decision based on library diversity or research objectives (hit discovery vs lead optimization) on which implementation to use may lead to significant improvements.
Virtual Reality Exploration and Planning for Precision Colorectal Surgery.
Guerriero, Ludovica; Quero, Giuseppe; Diana, Michele; Soler, Luc; Agnus, Vincent; Marescaux, Jacques; Corcione, Francesco
2018-06-01
Medical software can build a digital clone of the patient with 3-dimensional reconstruction of Digital Imaging and Communication in Medicine images. The virtual clone can be manipulated (rotations, zooms, etc), and the various organs can be selectively displayed or hidden to facilitate a virtual reality preoperative surgical exploration and planning. We present preliminary cases showing the potential interest of virtual reality in colorectal surgery for both cases of diverticular disease and colonic neoplasms. This was a single-center feasibility study. The study was conducted at a tertiary care institution. Two patients underwent a laparoscopic left hemicolectomy for diverticular disease, and 1 patient underwent a laparoscopic right hemicolectomy for cancer. The 3-dimensional virtual models were obtained from preoperative CT scans. The virtual model was used to perform preoperative exploration and planning. Intraoperatively, one of the surgeons was manipulating the virtual reality model, using the touch screen of a tablet, which was interactively displayed to the surgical team. The main outcome was evaluation of the precision of virtual reality in colorectal surgery planning and exploration. In 1 patient undergoing laparoscopic left hemicolectomy, an abnormal origin of the left colic artery beginning as an extremely short common trunk from the inferior mesenteric artery was clearly seen in the virtual reality model. This finding was missed by the radiologist on CT scan. The precise identification of this vascular variant granted a safe and adequate surgery. In the remaining cases, the virtual reality model helped to precisely estimate the vascular anatomy, providing key landmarks for a safer dissection. A larger sample size would be necessary to definitively assess the efficacy of virtual reality in colorectal surgery. Virtual reality can provide an enhanced understanding of crucial anatomical details, both preoperatively and intraoperatively, which could