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Sample records for aided drug design

  1. Role of computer-aided drug design in modern drug discovery.

    PubMed

    Macalino, Stephani Joy Y; Gosu, Vijayakumar; Hong, Sunhye; Choi, Sun

    2015-09-01

    Drug discovery utilizes chemical biology and computational drug design approaches for the efficient identification and optimization of lead compounds. Chemical biology is mostly involved in the elucidation of the biological function of a target and the mechanism of action of a chemical modulator. On the other hand, computer-aided drug design makes use of the structural knowledge of either the target (structure-based) or known ligands with bioactivity (ligand-based) to facilitate the determination of promising candidate drugs. Various virtual screening techniques are now being used by both pharmaceutical companies and academic research groups to reduce the cost and time required for the discovery of a potent drug. Despite the rapid advances in these methods, continuous improvements are critical for future drug discovery tools. Advantages presented by structure-based and ligand-based drug design suggest that their complementary use, as well as their integration with experimental routines, has a powerful impact on rational drug design. In this article, we give an overview of the current computational drug design and their application in integrated rational drug development to aid in the progress of drug discovery research.

  2. Computer-Aided Drug Discovery and Design Targeting Ion Channels.

    PubMed

    Zhang, Qiansen; Gao, Zhaobing; Yang, Huaiyu

    2016-01-01

    Ion channels are widely expressed in living cells and play critical roles in various cellular biological functions. Dysfunctional ion channels can cause a variety of diseases, making ion channels attractive targets for drug discovery. Computational approaches, such as molecular docking and molecular dynamic simulations, provide economic and efficient tools for finding modulators of ion channels and for elucidating the action mechanisms of small molecules. In this review, we focus primarily on four types of ion channels (voltage-gated, ligand-gated, acid-sensing, and virus matrix 2 ion channels). The current advancements in computer-aided drug discovery and design targeting ion channels are summarized. First, ligand-based studies for drug design are briefly outlined. Then, we focus on the structurebased studies targeting pore domains, endogenous binding sites and allosteric sites of ion channels. Moreover, we also review the contribution of computational methods to the field of ligand binding and unbinding pathways of ion channels. Finally, we propose future developments for the field. PMID:26975507

  3. Anti AIDS drug design with the help of neural networks

    NASA Astrophysics Data System (ADS)

    Tetko, I. V.; Tanchuk, V. Yu.; Luik, A. I.

    1995-04-01

    Artificial neural networks were used to analyze and predict the human immunodefiency virus type 1 reverse transcriptase inhibitors. Training and control set included 44 molecules (most of them are well-known substances such as AZT, TIBO, dde, etc.) The biological activities of molecules were taken from literature and rated for two classes: active and inactive compounds according to their values. We used topological indices as molecular parameters. Four most informative parameters (out of 46) were chosen using cluster analysis and original input parameters' estimation procedure and were used to predict activities of both control and new (synthesized in our institute) molecules. We applied pruning network algorithm and network ensembles to obtain the final classifier and avoid chance correlation. The increasing of neural network generalization of the data from the control set was observed, when using the aforementioned methods. The prognosis of new molecules revealed one molecule as possibly active. It was confirmed by further biological tests. The compound was as active as AZT and in order less toxic. The active compound is currently being evaluated in pre clinical trials as possible drug for anti-AIDS therapy.

  4. Alzheimer's disease drug development based on Computer-Aided Drug Design.

    PubMed

    Zeng, Huahui; Wu, Xiangxiang

    2016-10-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the excessive deposition of amyloids in the brain. The pathological features mainly include the extracellular amyloid plaques and intracellular neurofibrillary tangles, which are the production of amyloid precursor protein (APP) processed by the α-, β- and γ-secretases. Based on the amyloid cascade hypotheses of AD, a large number of amyloid-β agents and secretase inhibitors against AD have been recently developed by using computational methods. This review article describes pathophysiology of AD and the structure of the Aβ plaques, β- and γ-secretases, and discusses the recent advances in the development of the amyloid agents for AD therapy and diagnosis by using Computer-Aided Drug Design approach.

  5. Recent advances in computer-aided drug design as applied to anti-influenza drug discovery.

    PubMed

    Mallipeddi, Prema L; Kumar, Gyanendra; White, Stephen W; Webb, Thomas R

    2014-01-01

    Influenza is a seasonal and serious health threat, and the recent outbreak of H7N9 following the pandemic spread of H1N1 in 2009 has served to emphasize the importance of anti-influenza drug discovery. Zanamivir (Relenza™) and oseltamivir (Tamiflu(®)) are two antiviral drugs currently recommended by the CDC for treating influenza. Both are examples of the successful application of structure-based drug design strategies. These strategies have combined computer- based approaches, such as docking- and pharmacophore-based virtual screening with X-ray crystallographic structural analyses. Docking is a routinely used computational method to identify potential hits from large compound libraries. This method has evolved from simple rigid docking approaches to flexible docking methods to handle receptor flexibility and to enhance hit rates in virtual screening. Virtual screening approaches can employ both ligand-based and structurebased pharmacophore models depending on the available information. The exponential growth in computing power has increasingly facilitated the application of computer-aided methods in drug discovery, and they now play significant roles in the search for novel therapeutics. An overview of these computational tools is presented in this review, and recent advances and challenges will be discussed. The focus of the review will be anti-influenza drug discovery and how advances in our understanding of viral biology have led to the discovery of novel influenza protein targets. Also discussed will be strategies to circumvent the problem of resistance emerging from rapid mutations that has seriously compromised the efficacy of current anti-influenza therapies.

  6. Computer-Aided Drug Design of Bioactive Natural Products.

    PubMed

    Prachayasittikul, Veda; Worachartcheewan, Apilak; Shoombuatong, Watshara; Songtawee, Napat; Simeon, Saw; Prachayasittikul, Virapong; Nantasenamat, Chanin

    2015-01-01

    Natural products have been an integral part of sustaining civilizations because of their medicinal properties. Past discoveries of bioactive natural products have relied on serendipity, and these compounds serve as inspiration for the generation of analogs with desired physicochemical properties. Bioactive natural products with therapeutic potential are abundantly available in nature and some of them are beyond exploration by conventional methods. The effectiveness of computational approaches as versatile tools for facilitating drug discovery and development has been recognized for decades, without exception, in the case of natural products. In the post-genomic era, scientists are bombarded with data produced by advanced technologies. Thus, rendering these data into knowledge that is interpretable and meaningful becomes an essential issue. In this regard, computational approaches utilize the existing data to generate knowledge that provides valuable understanding for addressing current problems and guiding the further research and development of new natural-derived drugs. Furthermore, several medicinal plants have been continuously used in many traditional medicine systems since antiquity throughout the world, and their mechanisms have not yet been elucidated. Therefore, the utilization of computational approaches and advanced synthetic techniques would yield great benefit to improving the world's health population and well-being. PMID:25961523

  7. Computer-Aided Drug Design of Bioactive Natural Products.

    PubMed

    Prachayasittikul, Veda; Worachartcheewan, Apilak; Shoombuatong, Watshara; Songtawee, Napat; Simeon, Saw; Prachayasittikul, Virapong; Nantasenamat, Chanin

    2015-01-01

    Natural products have been an integral part of sustaining civilizations because of their medicinal properties. Past discoveries of bioactive natural products have relied on serendipity, and these compounds serve as inspiration for the generation of analogs with desired physicochemical properties. Bioactive natural products with therapeutic potential are abundantly available in nature and some of them are beyond exploration by conventional methods. The effectiveness of computational approaches as versatile tools for facilitating drug discovery and development has been recognized for decades, without exception, in the case of natural products. In the post-genomic era, scientists are bombarded with data produced by advanced technologies. Thus, rendering these data into knowledge that is interpretable and meaningful becomes an essential issue. In this regard, computational approaches utilize the existing data to generate knowledge that provides valuable understanding for addressing current problems and guiding the further research and development of new natural-derived drugs. Furthermore, several medicinal plants have been continuously used in many traditional medicine systems since antiquity throughout the world, and their mechanisms have not yet been elucidated. Therefore, the utilization of computational approaches and advanced synthetic techniques would yield great benefit to improving the world's health population and well-being.

  8. Harnessing Polypharmacology with Computer-Aided Drug Design and Systems Biology.

    PubMed

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

    2016-01-01

    The ascent of polypharmacology in drug development has many implications for disease therapy, most notably in the efforts of drug discovery, drug repositioning, precision medicine and combination therapy. The single- target approach to drug development has encountered difficulties in predicting drugs that are both clinically efficacious and avoid toxicity. By contrast, polypharmacology offers the possibility of a controlled distribution of effects on a biological system. This review addresses possibilities and bottlenecks in the efficient computational application of polypharmacology. The two major areas we address are the discovery and prediction of multiple protein targets using the tools of computer-aided drug design, and the use of these protein targets in predicting therapeutic potential in the context of biological networks. The successful application of polypharmacology to systems biology and pharmacology has the potential to markedly accelerate the pace of development of novel therapies for multiple diseases, and has implications for the intellectual property landscape, likely requiring targeted changes in patent law. PMID:26907947

  9. Harnessing Polypharmacology with Computer-Aided Drug Design and Systems Biology.

    PubMed

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

    2016-01-01

    The ascent of polypharmacology in drug development has many implications for disease therapy, most notably in the efforts of drug discovery, drug repositioning, precision medicine and combination therapy. The single- target approach to drug development has encountered difficulties in predicting drugs that are both clinically efficacious and avoid toxicity. By contrast, polypharmacology offers the possibility of a controlled distribution of effects on a biological system. This review addresses possibilities and bottlenecks in the efficient computational application of polypharmacology. The two major areas we address are the discovery and prediction of multiple protein targets using the tools of computer-aided drug design, and the use of these protein targets in predicting therapeutic potential in the context of biological networks. The successful application of polypharmacology to systems biology and pharmacology has the potential to markedly accelerate the pace of development of novel therapies for multiple diseases, and has implications for the intellectual property landscape, likely requiring targeted changes in patent law.

  10. Current Status of Computer-Aided Drug Design for Type 2 Diabetes

    PubMed Central

    Bibi, Shabana; Sakata, Katsumi

    2016-01-01

    Background Diabetes is a metabolic disorder that requires multiple therapeutic approaches. The pancreas loses its functionality to properly produce the insulin hormone in patients with diabetes mellitus. In 2012, more than one million people worldwide died as a result of diabetes, which was the eighth leading cause of death. Objective Most drugs currently available and approved by the U.S. Food and Drug Administration cannot reach an adequate level of glycemic control in diabetic patients, and have many side effects; thus, new classes of compounds are required. Efforts based on computer-aided drug design (CADD) can mine a large number of databases to produce new and potent hits and minimize the requirement of time and dollars for new discoveries. Methods Pharmaceutical sciences have made progress with advances in drug design concepts. Virtual screening of large databases is most compatible with different computational methods such as molecular docking, pharmacophore, quantitative structure-activity relationship, and molecular dynamic simulation. Contribution of these methods in selection of antidiabetic compounds has been discussed. Results The Computer-Aided Drug Design (CADD) approach has contributed to successful discovery of novel anti-diabetic agents. This mini-review focuses on CADD approach on currently approved drugs and new therapeutic agents-in-development that may achieve suitable glucose levels and decrease the risk of hypoglycemia, which is a major obstacle to glucose control and a special concern for therapies that increase insulin levels. Conclusion Drug design and development for type 2 diabetes have been actively studied. However, a large number of antidiabetic drugs are still in early stages of development. The conventional target- and structure-based approaches can be regarded as part of the efforts toward therapeutic mechanism-based drug design for treatment of type 2 diabetes. It is expected that further improvement in CADD approach will

  11. Potential Drug-Like Inhibitors of Group 1 Influenza Neuraminidase Identified through Computer-Aided Drug Design

    PubMed Central

    Durrant, Jacob D.; McCammon, J. Andrew

    2010-01-01

    Pandemic (H1N1) influenza poses an imminent threat. Nations have stockpiled inhibitors of the influenza protein neuraminidase in hopes of protecting their citizens, but drug-resistant strains have already emerged, and novel therapeutics are urgently needed. In the current work, the computer program AutoGrow is used to generate novel predicted neuraminidase inhibitors. Given the great flexibility of the neuraminidase active site, protein dynamics are also incorporated into the computer-aided drug-design process. Several potential inhibitors are identified that are predicted to bind neuraminidase better than currently approved drugs. PMID:20427241

  12. Design, Development, and Evaluation of Visual Aids for Communicating Prescription Drug Instructions to Nonliterate Patients in Rural Cameroon.

    ERIC Educational Resources Information Center

    Ngoh, Lucy N.; Shepherd, Marvin D.

    1997-01-01

    Culturally sensitive visual aids designed to help convey drug information to nonliterate female adults requiring antibiotics were developed. Researchers conceptualized the messages, and a local artist produced the visual aids. Comprehension and compliance with prescription instructions were evaluated (N=78). Results and practical implications are…

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

    PubMed

    Güner, Osman F

    2002-12-01

    With computer-aided drug design established as an integral part of the lead discovery and optimization process, pharmacophores have become a focal point for conceptualizing and understanding receptor-ligand interactions. In the structure-based design process, pharmacophores can be used to align molecules based on the three-dimensional arrangement of chemical features or to develop predictive models (e.g., 3D-QSAR) that correlate with the experimental activities of a given training set. Pharmacophores can be also used as search queries for retrieving potential leads from structural databases, for designing molecules with specific desired attributes, or as fingerprints for assessing similarity and diversity of molecules. This review article presents a historical perspective on the evolution and use of the pharmacophore concept in the pharmaceutical, biotechnology, and fragrances industry with published examples of how the technology has contributed and advanced the field. PMID:12470283

  14. e-LEA3D: a computational-aided drug design web server.

    PubMed

    Douguet, Dominique

    2010-07-01

    e-LEA3D web server integrates three complementary tools to perform computer-aided drug design based on molecular fragments. In drug discovery projects, there is a considerable interest in identifying novel and diverse molecular scaffolds to enhance chances of success. The de novo drug design tool is used to invent new ligands to optimize a user-specified scoring function. The composite scoring function includes both structure- and ligand-based evaluations. The de novo approach is an alternative to a blind virtual screening of large compound collections. A heuristic based on a genetic algorithm rapidly finds which fragments or combination of fragments fit a QSAR model or the binding site of a protein. While the approach is ideally suited for scaffold-hopping, this module also allows a scan for possible substituents to a user-specified scaffold. The second tool offers a traditional virtual screening and filtering of an uploaded library of compounds. The third module addresses the combinatorial library design that is based on a user-drawn scaffold and reactants coming, for example, from a chemical supplier. The e-LEA3D server is available at: http://bioinfo.ipmc.cnrs.fr/lea.html.

  15. e-LEA3D: a computational-aided drug design web server

    PubMed Central

    Douguet, Dominique

    2010-01-01

    e-LEA3D web server integrates three complementary tools to perform computer-aided drug design based on molecular fragments. In drug discovery projects, there is a considerable interest in identifying novel and diverse molecular scaffolds to enhance chances of success. The de novo drug design tool is used to invent new ligands to optimize a user-specified scoring function. The composite scoring function includes both structure- and ligand-based evaluations. The de novo approach is an alternative to a blind virtual screening of large compound collections. A heuristic based on a genetic algorithm rapidly finds which fragments or combination of fragments fit a QSAR model or the binding site of a protein. While the approach is ideally suited for scaffold-hopping, this module also allows a scan for possible substituents to a user-specified scaffold. The second tool offers a traditional virtual screening and filtering of an uploaded library of compounds. The third module addresses the combinatorial library design that is based on a user-drawn scaffold and reactants coming, for example, from a chemical supplier. The e-LEA3D server is available at: http://bioinfo.ipmc.cnrs.fr/lea.html. PMID:20444867

  16. Computer-Aided Drug Design (CADD): Methodological Aspects and Practical Applications in Cancer Research

    NASA Astrophysics Data System (ADS)

    Gianti, Eleonora

    Computer-Aided Drug Design (CADD) has deservedly gained increasing popularity in modern drug discovery (Schneider, G.; Fechner, U. 2005), whether applied to academic basic research or the pharmaceutical industry pipeline. In this work, after reviewing theoretical advancements in CADD, we integrated novel and stateof- the-art methods to assist in the design of small-molecule inhibitors of current cancer drug targets, specifically: Androgen Receptor (AR), a nuclear hormone receptor required for carcinogenesis of Prostate Cancer (PCa); Signal Transducer and Activator of Transcription 5 (STAT5), implicated in PCa progression; and Epstein-Barr Nuclear Antigen-1 (EBNA1), essential to the Epstein Barr Virus (EBV) during latent infections. Androgen Receptor. With the aim of generating binding mode hypotheses for a class (Handratta, V.D. et al. 2005) of dual AR/CYP17 inhibitors (CYP17 is a key enzyme for androgens biosynthesis and therefore implicated in PCa development), we successfully implemented a receptor-based computational strategy based on flexible receptor docking (Gianti, E.; Zauhar, R.J. 2012). Then, with the ultimate goal of identifying novel AR binders, we performed Virtual Screening (VS) by Fragment-Based Shape Signatures, an improved version of the original method developed in our Laboratory (Zauhar, R.J. et al. 2003), and we used the results to fully assess the high-level performance of this innovative tool in computational chemistry. STAT5. The SRC Homology 2 (SH2) domain of STAT5 is responsible for phospho-peptide recognition and activation. As a keystone of Structure-Based Drug Design (SBDD), we characterized key residues responsible for binding. We also generated a model of STAT5 receptor bound to a phospho-peptide ligand, which was validated by docking publicly known STAT5 inhibitors. Then, we performed Shape Signatures- and docking-based VS of the ZINC database (zinc.docking.org), followed by Molecular Mechanics Generalized Born Surface Area (MMGBSA

  17. Design, development, and evaluation of visual aids for communicating prescription drug instructions to nonliterate patients in rural Cameroon.

    PubMed

    Ngoh, L N; Shepherd, M D

    1997-03-01

    In this study, culturally sensitive visual aids designed to help convey drug information to nonliterate female adults who had a prescription for a solid oral dosage form of antibiotic medications were developed and evaluated. The researchers conceptualized the educational messages while a local artist produced the visual aids. Seventy-eight female ambulatory patients were evaluated for comprehension and compliance with antibiotic prescription instructions. The study was conducted in three health centers in Cameroon, West Africa and followed a pre-test, post-test, and follow-up format for three groups: two experimental, and one control. All participants were randomly assigned to either experimental or control groups, 26 patients to each group. Subjects in the experimental groups received visual aids alone or visual aids plus an Advanced Organizer. A comparison of the three groups showed that subjects in the experimental groups scored significantly higher than the control group in both the comprehension and compliance measures.

  18. Targeting HIV reverse transcriptase for anti-AIDS drug design: structural and biological considerations for chemotherapeutic strategies.

    PubMed

    Arnold, E; Das, K; Ding, J; Yadav, P N; Hsiou, Y; Boyer, P L; Hughes, S H

    1996-04-01

    The reverse transcriptase of HIV is a key target for the antiviral treatment of AIDS. Numerous potent inhibitors of RT have been described including all of the drugs that have been currently licensed for the treatment of AIDS, but their efficacy has been limited by the emergence of drug-resistant HIV variants. Extensive biochemical, genetic, and clinical data about HIV RT enzymatic mechanisms, inhibition, and drug resistance have been reported. This information, taken together with structural data from crystallographic studies of HIV-1 RT, has set the stage for structure-based design of improved inhibitors of this essential viral enzyme. Comparisons of the different crystal structures of HIV-1 RT shows that the enzyme has great conformational flexibility, providing additional possibilities for drug targeting. Recent clinical and virological data suggest that HIV-1 RT enzymes that carry drug-resistance mutations can be substantially impaired and that combinations of RT inhibitors can produce significant clinical benefit in the treatment of AIDS. An immediate goal is to use the available information to design specific inhibitors or combination therapies that will select for relatively less fit HIV variants.

  19. Molecular modeling and computer aided drug design. Examples of their applications in medicinal chemistry.

    PubMed

    Ooms, F

    2000-02-01

    The development of new drugs with potential therapeutic applications is one of the most complex and difficult process in the pharmaceutical industry. Millions of dollars and man-hours are devoted to the discovery of new therapeutical agents. As, the activity of a drug is the result of a multitude of factors such as bioavailability, toxicity and metabolism, rational drug design has been utopias for centuries. Very recently, impressive technological advances in areas such as structural characterization of biomacromolecules, computer sciences and molecular biology have made rational drug design feasible. The aim of this review is to give an outline of studies in the field of medicinal chemistry in which molecular modeling has helped in the discovery process of new drugs. The emphasis will be on lead generation and optimization.

  20. Designing State Aid Formulas

    ERIC Educational Resources Information Center

    Zhao, Bo; Bradbury, Katharine

    2009-01-01

    This paper designs a new equalization-aid formula based on fiscal gaps of local communities. When states are in transition to a new local aid formula, the issue of whether and how to hold existing aid harmless poses a challenge. The authors show that some previous studies and the formulas derived from them give differential weights to existing and…

  1. AstexViewer: a visualisation aid for structure-based drug design.

    PubMed

    Hartshorn, Michael J

    2002-12-01

    AstexViewer is a Java molecular graphics program that can be used for visualisation in many aspects of structure-based drug design. This paper describes its functionality, implementation and examples of its use. The program can run as an Applet in a web browser allowing structures to be displayed without installing additional software. Applications of its use are described for visualisation and as part of a structure based design platform. The software is being made freely available to the community and may be downloaded from http://www.astex-technology.com/AstexViewer. PMID:12825620

  2. Computer-aided design of liposomal drugs: In silico prediction and experimental validation of drug candidates for liposomal remote loading.

    PubMed

    Cern, Ahuva; Barenholz, Yechezkel; Tropsha, Alexander; Goldblum, Amiram

    2014-01-10

    Previously we have developed and statistically validated Quantitative Structure Property Relationship (QSPR) models that correlate drugs' structural, physical and chemical properties as well as experimental conditions with the relative efficiency of remote loading of drugs into liposomes (Cern et al., J. Control. Release 160 (2012) 147-157). Herein, these models have been used to virtually screen a large drug database to identify novel candidate molecules for liposomal drug delivery. Computational hits were considered for experimental validation based on their predicted remote loading efficiency as well as additional considerations such as availability, recommended dose and relevance to the disease. Three compounds were selected for experimental testing which were confirmed to be correctly classified by our previously reported QSPR models developed with Iterative Stochastic Elimination (ISE) and k-Nearest Neighbors (kNN) approaches. In addition, 10 new molecules with known liposome remote loading efficiency that were not used by us in QSPR model development were identified in the published literature and employed as an additional model validation set. The external accuracy of the models was found to be as high as 82% or 92%, depending on the model. This study presents the first successful application of QSPR models for the computer-model-driven design of liposomal drugs.

  3. Computer-aided design of liposomal drugs: in silico prediction and experimental validation of drug candidates for liposomal remote loading

    PubMed Central

    Cern, Ahuva; Barenholz, Yechezkel; Tropsha, Alexander; Goldblum, Amiram

    2014-01-01

    Previously we have developed and statistically validated Quantitative Structure Property Relationship (QSPR) models that correlate drugs’ structural, physical and chemical properties as well as experimental conditions with the relative efficiency of remote loading of drugs into liposomes (Cern et al, Journal of Controlled Release, 160(2012) 14–157). Herein, these models have been used to virtually screen a large drug database to identify novel candidate molecules for liposomal drug delivery. Computational hits were considered for experimental validation based on their predicted remote loading efficiency as well as additional considerations such as availability, recommended dose and relevance to the disease. Three compounds were selected for experimental testing which were confirmed to be correctly classified by our previously reported QSPR models developed with Iterative Stochastic Elimination (ISE) and k-nearest neighbors (kNN) approaches. In addition, 10 new molecules with known liposome remote loading efficiency that were not used in QSPR model development were identified in the published literature and employed as an additional model validation set. The external accuracy of the models was found to be as high as 82% or 92%, depending on the model. This study presents the first successful application of QSPR models for the computer-model-driven design of liposomal drugs. PMID:24184343

  4. Computer-aided drug discovery

    PubMed Central

    Bajorath, Jürgen

    2015-01-01

    Computational approaches are an integral part of interdisciplinary drug discovery research. Understanding the science behind computational tools, their opportunities, and limitations is essential to make a true impact on drug discovery at different levels. If applied in a scientifically meaningful way, computational methods improve the ability to identify and evaluate potential drug molecules, but there remain weaknesses in the methods that preclude naïve applications. Herein, current trends in computer-aided drug discovery are reviewed, and selected computational areas are discussed. Approaches are highlighted that aid in the identification and optimization of new drug candidates. Emphasis is put on the presentation and discussion of computational concepts and methods, rather than case studies or application examples. As such, this contribution aims to provide an overview of the current methodological spectrum of computational drug discovery for a broad audience. PMID:26949519

  5. Drug use first aid

    MedlinePlus

    ... addiction is gradual. And some drugs (such as cocaine ) can cause addiction after only a few doses. ... Saunders; 2013:chap 150. Rao RB, Hoffman RS. Cocaine and other sympathomimetics. In: Marx JA, Hockberger RS, ...

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

    SciTech Connect

    1996-09-23

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

  7. Computer Aided Drug Design Approaches for Identification of Novel Autotaxin (ATX) Inhibitors.

    PubMed

    Vrontaki, Eleni; Melagraki, Georgia; Kaffe, Eleanna; Mavromoustakos, Thomas; Kokotos, George; Aidinis, Vassilis; Afantitis, Antreas

    2016-01-01

    Autotaxin (ATX) has become an attractive target with a huge pharmacological and pharmacochemical interest in LPA-related diseases and to date many small organic molecules have been explored as potential ATX inhibitors. As a useful aid in the various efforts of identifying novel effective ATX inhibitors, in silico methods can serve as an important and valuable tool. Especially, Virtual Screening (VS) has recently received increased attention due to the large datasets made available, the development of advanced VS techniques and the encouraging fact that VS has contributed to the discovery of several compounds that have either reached the market or entered clinical trials. Different techniques and workflows have been reported in literature with the goal to prioritize possible potent hits. In this review article several deployed virtual screening strategies for the identification of novel potent ATX inhibitors are described. PMID:26997151

  8. Creating Novel Activated Factor XI Inhibitors through Fragment Based Lead Generation and Structure Aided Drug Design

    PubMed Central

    Fjellström, Ola; Akkaya, Sibel; Beisel, Hans-Georg; Eriksson, Per-Olof; Erixon, Karl; Gustafsson, David; Jurva, Ulrik; Kang, Daiwu; Karis, David; Knecht, Wolfgang; Nerme, Viveca; Nilsson, Ingemar; Olsson, Thomas; Redzic, Alma; Roth, Robert; Sandmark, Jenny; Tigerström, Anna; Öster, Linda

    2015-01-01

    Activated factor XI (FXIa) inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1’-S2’ FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1’-S2’ binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC50 of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1’-S2’ binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds. PMID:25629509

  9. Identification and Validation of Human DNA Ligase Inhibitors Using Computer-Aided Drug Design

    PubMed Central

    Zhong, Shijun; Chen, Xi; Zhu, Xiao; Dziegielewska, Barbara; Bachman, Kurtis E.; Ellenberger, Tom; Ballin, Jeff D.; Wilson, Gerald M.; Tomkinson, Alan E.; MacKerell, Alexander D.

    2009-01-01

    Linking together of DNA strands by DNA ligases is essential for DNA replication and repair. Since many therapies used to treat cancer act by causing DNA damage, there is growing interest in the development of DNA repair inhibitors. Accordingly, virtual database screening and experimental evaluation were applied to identify inhibitors of human DNA ligase I (hLigI). When a DNA binding site within the DNA binding domain (DBD) of hLigI was targeted, more than 1 million compounds were screened from which 192 were chosen for experimental evaluation. In DNA joining assays, 10 compounds specifically inhibited hLigI, 5 of which also inhibited the proliferation of cultured human cell lines. Analysis of the 10 active compounds revealed the utility of including multiple protein conformations and chemical clustering in the virtual screening procedure. The identified ligase inhibitors are structurally diverse and have druglike physical and molecular characteristics making them ideal for further drug development studies. PMID:18630893

  10. A pocket aide-memoire on drug interactions.

    PubMed

    Stockley, I H

    1975-04-01

    A pocket size "slide-rule" type device designed to be used by physicians, pharmacists and nurses as a memory aid on potential drug-drug interactions is described. Color-coded symbols on the device indicate both the type and clinical significance of the potential interactions involving 56 drugs or groups of drugs.

  11. Drug Convictions May Affect Your Student Aid.

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

    This booklet explains problems posed by prior drug convictions to college-bound students seeking federal financial aid. Under a new law which takes effect on July 1, 2000, some students who have drug convictions may be ineligible for federal student aid. For possession of illegal drugs, students are ineligible from the date of conviction for one…

  12. Abelson tyrosine-protein kinase 1 as principal target for drug discovery against leukemias. Role of the current computer-aided drug design methodologies.

    PubMed

    Speck-Planche, Alejandro; Luan, Feng; Cordeiro, M N D S

    2012-01-01

    The discovery of anti-cancer agents is an area which continues in accelerated expansion. Leukemias (Lkms) are among the most investigated cancers due to its high and dominant prevalence in children. Computer-aided drug design (CADD) methodologies have been extremely important for the discovery of potent anti-Lkms agents, providing essential insights about the molecular patterns which could be involved in the appearance and development of anti-Lkms activity. The present review is focused on the role of the current CADD methodologies for the discovery of anti-Lkms agents with strong emphasis on the in silico prediction of inhibitors against the primary protein associated with the appearance of Lkms: Abelson tyrosine-protein kinase 1 (TPK-ABL1). In order to make a contribution to the field, we also developed a unified ligand-based approach by exploring Quantitative-Structure Activity Relationships (QSAR) studies. Here, we focused on the construction of two multi-targets (mt) QSAR models by employing a large and heterogeneous database of compounds. These models exhibited excellent statistical quality and predictive power to classifying more than 92% of inhibitors/ no inhibitors against seven proteins associated with Lkms, in both training and prediction sets. By using our unified ligand-based approach we identified several fragments as responsible for the anti-Lkms activity through inhibition of proteins, and new molecules were suggested as versatile inhibitors of the seven proteins under study.

  13. Professional attitude of health care workers toward serving HIV/AIDS patients and drug users: questionnaire design and evaluation of reliability and validity.

    PubMed

    See, Lai-Chu; Shen, Yu-Ming; Chen, Chia-Ling; Huang, Tsuei-Mi; Huang, Yi-Hua; Huang, Hui-Chun; Lin, Sheue-Rong

    2011-11-01

    The manner in which health care workers (HCWs) interact with HIV/AIDS patients and drug users during their work clearly influences the sustainability of harm reduction programs. To evaluate the professional attitudes of HCWs, we designed a questionnaire with four constructs - discrimination, acceptance of HIV/AIDS patients, acceptance of drug users, and fear - and tested its reliability and validity. Ten experts rated the questionnaire and the mean content validity index was 85.6%. Analysis of 251 anonymous questionnaires from HCWs in Taiwan yielded a composite reliability and Cronbach's α for the four constructs of >0.7. First-order and second-order confirmatory factor analysis revealed a χ(2)/degrees of freedom <3, goodness-of-fit index (GFI) >0.9, adjusted goodness-of-fit index (AGFI) >0.9, Bentler-Bonnett normal fix index >0.9, and a root mean square error of approximation between 0.00 and 0.07 indicating a good fit of the model. HCWs with training in HRPs or AIDS prevention had higher questionnaire scores than those without such training, indicating good known-group validity.

  14. Computer-aided antibody design

    PubMed Central

    Kuroda, Daisuke; Shirai, Hiroki; Jacobson, Matthew P.; Nakamura, Haruki

    2012-01-01

    Recent clinical trials using antibodies with low toxicity and high efficiency have raised expectations for the development of next-generation protein therapeutics. However, the process of obtaining therapeutic antibodies remains time consuming and empirical. This review summarizes recent progresses in the field of computer-aided antibody development mainly focusing on antibody modeling, which is divided essentially into two parts: (i) modeling the antigen-binding site, also called the complementarity determining regions (CDRs), and (ii) predicting the relative orientations of the variable heavy (VH) and light (VL) chains. Among the six CDR loops, the greatest challenge is predicting the conformation of CDR-H3, which is the most important in antigen recognition. Further computational methods could be used in drug development based on crystal structures or homology models, including antibody–antigen dockings and energy calculations with approximate potential functions. These methods should guide experimental studies to improve the affinities and physicochemical properties of antibodies. Finally, several successful examples of in silico structure-based antibody designs are reviewed. We also briefly review structure-based antigen or immunogen design, with application to rational vaccine development. PMID:22661385

  15. Telerobotic workstation design aid

    NASA Technical Reports Server (NTRS)

    Corker, K.; Hudlicka, E.; Young, D.; Cramer, N.

    1989-01-01

    Telerobot systems are being developed to support a number of space mission applications. In low earth orbit, telerobots and teleoperated manipulators will be used in shuttle operations and space station construction/maintenance. Free flying telerobotic service vehicles will be used at low and geosynchronous orbital operations. Rovers and autonomous vehicles will be equipped with telerobotic devices in planetary exploration. In all of these systems, human operators will interact with the robot system at varied levels during the scheduled operations. The human operators may be in either orbital or ground-based control systems. To assure integrated system development and maximum utility across these systems, designers must be sensitive to the constraints and capabilities that the human brings to system operation and must be assisted in applying these human factors to system development. The simulation and analysis system is intended to serve the needs of system analysis/designers as an integrated workstation in support of telerobotic design.

  16. Can AIDS drugs be afforded?

    PubMed

    1997-11-01

    UNAIDS has launched an 'HIV Drug Access Initiative' in the Ivory Coast, Uganda, Chile, and Vietnam; the pilot project will attempt to improve access to HIV drugs. Public and private sector efforts will be coordinated. The Glaxo Wellcome, Hoffman-La Roche, and Virco pharmaceutical companies will participate. Each country will 1) adapt its present system with regard to HIV and 2) establish both an HIV drug advisory board and a non-profit company which will import the drugs. Health ministries within each country will be required to find sources of funding for the programs. Uganda will probably use funds from its sexually transmitted disease (STD) program, which is supported by the World Bank; the Ivory Coast will combine corporate contributions, new tariffs, and non-profit insurance system monies into a 'solidarity fund.' UNAIDS funds will be used for oversight and evaluation. UNAIDS also released a review of 68 studies which examined the impact of sex education on the sex behavior of young people; it indicated that, in 65 of the studies, sex education did not increase the sexual activity of youth. UNAIDS concluded that quality programs helped delay first intercourse and often reduced the number of sexual partners, resulting in reduced rates of STDs and unplanned pregnancy. UNAIDS further concluded that effective sex education should begin before the onset of sexual activity, and curriculums should be focused. Openness in communicating about sex should be encouraged, and social and media influences on behavior should be addressed. Young people should be taught negotiating skills (how to say 'no' to sex and how to insist on safer sex). PMID:12348380

  17. Can AIDS drugs be afforded?

    PubMed

    1997-11-01

    UNAIDS has launched an 'HIV Drug Access Initiative' in the Ivory Coast, Uganda, Chile, and Vietnam; the pilot project will attempt to improve access to HIV drugs. Public and private sector efforts will be coordinated. The Glaxo Wellcome, Hoffman-La Roche, and Virco pharmaceutical companies will participate. Each country will 1) adapt its present system with regard to HIV and 2) establish both an HIV drug advisory board and a non-profit company which will import the drugs. Health ministries within each country will be required to find sources of funding for the programs. Uganda will probably use funds from its sexually transmitted disease (STD) program, which is supported by the World Bank; the Ivory Coast will combine corporate contributions, new tariffs, and non-profit insurance system monies into a 'solidarity fund.' UNAIDS funds will be used for oversight and evaluation. UNAIDS also released a review of 68 studies which examined the impact of sex education on the sex behavior of young people; it indicated that, in 65 of the studies, sex education did not increase the sexual activity of youth. UNAIDS concluded that quality programs helped delay first intercourse and often reduced the number of sexual partners, resulting in reduced rates of STDs and unplanned pregnancy. UNAIDS further concluded that effective sex education should begin before the onset of sexual activity, and curriculums should be focused. Openness in communicating about sex should be encouraged, and social and media influences on behavior should be addressed. Young people should be taught negotiating skills (how to say 'no' to sex and how to insist on safer sex).

  18. Fragment-based approaches and computer-aided drug discovery.

    PubMed

    Rognan, Didier

    2012-01-01

    Fragment-based design has significantly modified drug discovery strategies and paradigms in the last decade. Besides technological advances and novel therapeutic avenues, one of the most significant changes brought by this new discipline has occurred in the minds of drug designers. Fragment-based approaches have markedly impacted rational computer-aided design both in method development and in applications. The present review illustrates the importance of molecular fragments in many aspects of rational ligand design, and discusses how thinking in "fragment space" has boosted computational biology and chemistry. PMID:21710380

  19. Computer aided flexible envelope designs

    NASA Technical Reports Server (NTRS)

    Resch, R. D.

    1975-01-01

    Computer aided design methods are presented for the design and construction of strong, lightweight structures which require complex and precise geometric definition. The first, flexible structures, is a unique system of modeling folded plate structures and space frames. It is possible to continuously vary the geometry of a space frame to produce large, clear spans with curvature. The second method deals with developable surfaces, where both folding and bending are explored with the observed constraint of available building materials, and what minimal distortion result in maximum design capability. Alternative inexpensive fabrication techniques are being developed to achieve computer defined enclosures which are extremely lightweight and mathematically highly precise.

  20. Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design.

    PubMed

    Hargrove, Tatiana Y; Friggeri, Laura; Wawrzak, Zdzislaw; Sivakumaran, Suneethi; Yazlovitskaya, Eugenia M; Hiebert, Scott W; Guengerich, F Peter; Waterman, Michael R; Lepesheva, Galina I

    2016-08-01

    Rapidly multiplying cancer cells synthesize greater amounts of cholesterol to build their membranes. Cholesterol-lowering drugs (statins) are currently in clinical trials for anticancer chemotherapy. However, given at higher doses, statins cause serious side effects by inhibiting the formation of other biologically important molecules derived from mevalonate. Sterol 14α-demethylase (CYP51), which acts 10 steps downstream, is potentially a more specific drug target because this portion of the pathway is fully committed to cholesterol production. However, screening a variety of commercial and experimental inhibitors of microbial CYP51 orthologs revealed that most of them (including all clinical antifungals) weakly inhibit human CYP51 activity, even if they display high apparent spectral binding affinity. Only one relatively potent compound, (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VFV), was identified. VFV has been further tested in cellular experiments and found to decrease proliferation of different cancer cell types. The crystal structures of human CYP51-VFV complexes (2.0 and 2.5 Å) both display a 2:1 inhibitor/enzyme stoichiometry, provide molecular insights regarding a broader substrate profile, faster catalysis, and weaker susceptibility of human CYP51 to inhibition, and outline directions for the development of more potent inhibitors.

  1. Drug abuse treatment as AIDS prevention.

    PubMed Central

    Metzger, D S; Navaline, H; Woody, G E

    1998-01-01

    OBJECTIVE: As the acquired immunodeficiency syndrome (AIDS) epidemic among drug users enters its third decade in the United States, it is important to consider the role playing by substance abuse treatment in the prevention of human immunodeficiency virus (HIV) infection. METHODS: The authors review the research literature, examining findings from studies with behavioral and serologic measures on the association among treatment participation, HIV risk reduction, and HIV infection. RESULTS: Numerous studies have now documented that significantly lower rates of drug use and related risk behaviors are practiced by injecting drug users (IDUs) who are in treatment. Importantly, these behavioral differences, based primarily on self-report, are consistent with studies that have examined HIV seroprevalence and seroincidence among drug users. CONCLUSION: The underlying mechanism of action suggested by the collective findings of the available literature is rather simple-- individuals who enter and remain in treatment reduce their drug use, when leads to fewer instances of drug-related risk behavior. This lower rate of exposure results in fewer infections with HIV. The protective effects of treatment, however, can only be achieved when programs are accessible and responsive to the changing needs of drug users. Future research needs to be directed at developing a better understanding of the factors that enhance treatment entry and retention. PMID:9722815

  2. Aids to School Bus Design

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Navistar International Transportation Corporation, Chicago, IL, used three separate NASA-developed technologies in the design and testing of their 3000 Series Bus Chassis which was developed expressly for school bus applications. For structural analysis, they used the MSC/NASTRAN program which mathematically analyzes a design and predicts how it will hold up under stress. They also used the SPATE 9000 system for non-contact measurement of stress, load transfer mechanisms, detection of hidden flaws, and monitoring structural changes during fatigue testing. SPATE 9000 was based on infrared stress measurement technology developed by Langley Research Center. They also employed the Wyle Ride Quality Meter, which was developed by Langley to aid in passenger aircraft design by providing an accurate measurement of ride vibration and sound level. These numbers translate into a subjective discomfort level index. These technologies contribute to the company's 45-48 percent share of the school bus chassis market.

  3. Computer-aided system design

    NASA Technical Reports Server (NTRS)

    Walker, Carrie K.

    1991-01-01

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

  4. EGRAM- ECHELLE SPECTROGRAPH DESIGN AID

    NASA Technical Reports Server (NTRS)

    Dantzler, A. A.

    1994-01-01

    EGRAM aids in the design of spectrographic systems that utilize an echelle-first order cross disperser combination. This optical combination causes a two dimensional echellogram to fall on a detector. EGRAM describes the echellogram with enough detail to allow the user to effectively judge the feasibility of the spectrograph's design. By iteratively altering system parameters, the desired echellogram can be achieved without making a physical model. EGRAM calculates system parameters which are accurate to the first order and compare favorably to results from ray tracing techniques. The spectrographic system modelled by EGRAM consists of an entrance aperture, collimator, echelle, cross dispersion grating, focusing options, and a detector. The system is assumed to be free of aberrations and the echelle, cross disperser, and detector should be planar. The EGRAM program is menu driven and has a HELP facility. The user is prompted for information such as minimum and maximum wavelengths, slit dimensions, ruling frequencies, detector geometry, and angle of incidence. EGRAM calculates the resolving power and range of order numbers covered by the echellogram. A numerical map is also produced. This tabulates the order number, slit bandpass, and high/middle/low wavelengths. EGRAM can also compute the centroid coordinates of a specific wavelength and order (or vice versa). EGRAM is written for interactive execution and is written in Microsoft BASIC A. It has been implemented on an IBM PC series computer operating under DOS. EGRAM was developed in 1985.

  5. Assessment of AIDS Risk among Treatment Seeking Drug Abusers.

    ERIC Educational Resources Information Center

    Black, John L.; And Others

    Intravenous (IV) drug abusers are at risk for contracting transmittable diseases such as acquired immunodeficiency syndrome (AIDS) and hepatitis B. This study was conducted to investigate the prevalence of risk behaviors for acquiring and transmitting AIDS and hepatitis B among treatment-seeking drug abusers (N=168). Subjects participated in a…

  6. Examining non-AIDS mortality among people who inject drugs

    PubMed Central

    Mathers, Bradley M.; Degenhardt, Louisa

    2014-01-01

    Objective: To systematically review and analyse data from cohorts of people who inject drugs (PWID) to improve existing estimates of non-AIDS mortality used to calculate mortality among PWID in the Spectrum Estimates and Projection Package. Design: Systematic review and meta-analysis. Methods: We conducted an update of an earlier systematic review of mortality among PWID, searching specifically for studies providing data on non-AIDS-related deaths. Random-effects meta-analyses were performed to derive pooled estimates of non-AIDS crude mortality rates across cohorts disaggregated by sex, HIV status and periods in and out of opioid substitution therapy (OST). Within each cohort, ratios of non-AIDS CMRs were calculated and then pooled across studies for the following paired sub-groups: HIV-negative versus HIV-positive PWID; male versus female PWID; periods in OST versus out of OST. For each analysis, pooled estimates by country income group and by geographic region were also calculated. Results: Thirty-seven eligible studies from high-income countries and five from low and middle-income countries were found. Non-AIDS mortality was significantly higher in low and middle-income countries [2.74 per 100 person-years; 95% confidence interval (CI) 1.76–3.72] than in high-income countries (1.56 per 100 person-years; 95% CI 1.38–1.74). Non-AIDS CMRs were 1.34 times greater among men than women (95% CI 1.14–1.57; N = 19 studies); 1.50 times greater among HIV-positive than HIV-negative PWID (95% CI 1.15, 1.96; N = 16 studies); and more than three times greater during periods out of OST than for periods on OST (N = 7 studies). Conclusions: A comprehensive response to injecting drug must include efforts to reduce the high levels of non-AIDS mortality among PWID. Due to limitations of currently available data, including substantial heterogeneity between studies, estimates of non-AIDS mortality specific to geographic regions, country income level, or the

  7. Computer Aided Design in Engineering Education.

    ERIC Educational Resources Information Center

    Gobin, R.

    1986-01-01

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

  8. [New pediatric drug dosage aids. Improving patient safety].

    PubMed

    Strauß, J M

    2016-03-01

    Dosing errors when administering medicine to children occur often and are due, e.g., to the commonly required dilution of the drugs, misjudgment of the patient's weight, confusion between drugs with similar names, and inadequate communication. Various aids (e.g., measuring tapes and dilution tables) have been designed to avoid mistakes to the greatest extent possible. In daily clinical practice, books and pocket cards are still used for rapid orientation. Use of smartphone-based apps continues to increase, whereby the user is ultimately responsible for their validity. In clinical practice, the simplest possible strategies should be used. A culture that encourages disclosure of errors is useful in order to optimize processes and avoid future errors.

  9. Photogrammetry and computer-aided piping design

    SciTech Connect

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

    1985-02-18

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

  10. Uncertainty management in intelligent design aiding systems

    NASA Technical Reports Server (NTRS)

    Brown, Donald E.; Gabbert, Paula S.

    1988-01-01

    A novel approach to uncertainty management which is particularly effective in intelligent design aiding systems for large-scale systems is presented. The use of this approach in the materials handling system design domain is discussed. It is noted that, during any point in the design process, a point value can be obtained for the evaluation of feasible designs; however, the techniques described provide unique solutions for these point values using only the current information about the design environment.

  11. Poverty, drug abuse fuel Caribbean AIDS outbreak.

    PubMed

    Kovaleski, S F

    1998-01-01

    Hatred and fear of homosexuals, together with a fear of losing tourism revenue, drove many high-level policymakers in the Caribbean to ignore the HIV/AIDS in its infancy. With an annual incidence rate of at least 146.6 people per 100,000, the Bahamas now has one of the highest AIDS rates in the world and the highest such rate in the English-speaking Caribbean. AIDS has become the major cause of death for men and women aged 20-44 in the Bahamas. Indeed, throughout the Caribbean, countries like the Bahamas must now cope with a growing AIDS epidemic. UN AIDS Program figures indicate that at least 310,000 people in the Caribbean have either HIV infection or AIDS, and that the prevalence rate among adults is almost 2%. This compares with an estimated 7.4% of the adult population of sub-Saharan Africa which is infected and 0.6% of adults in North America. 65% of reported AIDS cases in the region result from heterosexual intercourse. While the annual number of AIDS cases has been falling in North America over the last several years and rates in Latin America have leveled off, rates in the Caribbean are increasing sharply. Poverty, the population's lack of awareness, low levels of education, internal and international migration, crack cocaine use, promiscuity, high levels of STDs, prostitution, and tourism are also facilitating the spread of HIV in the Caribbean. Social conservatism, mainly in the English-Caribbean, about discussing sex impedes the implementation and success of HIV/AIDS prevention interventions.

  12. Aids in designing laboratory flumes

    USGS Publications Warehouse

    Williams, Garnett P.

    1971-01-01

    The upsurge of interest in our environment has caused research and instruction in the flow of water along open channels to become increasingly popular in universities and institutes. This, in turn, has brought a greater demand for properly-designed laboratory flumes. Whatever the reason for your interest, designing and building the flume will take a little preparation. You may choose a pattern exactly like a previous design, or you may follow the more time-consuming method of studying several existing flumes and combine the most desirable features of each.

  13. Drug Design and Emotion

    NASA Astrophysics Data System (ADS)

    Folkers, Gerd; Wittwer, Amrei

    2007-11-01

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

  14. A rule based computer aided design system

    NASA Technical Reports Server (NTRS)

    Premack, T.

    1986-01-01

    A Computer Aided Design (CAD) system is presented which supports the iterative process of design, the dimensional continuity between mating parts, and the hierarchical structure of the parts in their assembled configuration. Prolog, an interactive logic programming language, is used to represent and interpret the data base. The solid geometry representing the parts is defined in parameterized form using the swept volume method. The system is demonstrated with a design of a spring piston.

  15. Essential drugs in AIDS care: issues of availability and affordability.

    PubMed

    Kaur, S R

    1996-01-01

    Several antiretroviral drugs against HIV/AIDS have been developed in recent years. These drugs, reverse transcriptase inhibitors and protease inhibitors, inhibit the reproduction of HIV, but do not eliminate the presence of HIV in the body. The cost of drugs to treat one person with HIV/AIDS easily runs into the thousands of US dollars per year. These new drugs are therefore routinely used in developed countries, but not among the masses in developing countries. Many of the drugs needed to treat the opportunistic infections present during advanced HIV infection and AIDS are also prohibitively expensive for both developing countries and most individuals in those countries. The imposition of World Bank and International Monetary Fund structural adjustment programs together with decreased household purchasing power during the 1990s has led to increased demand for public sector services amid reduced public expenditure. The private sector is increasingly taking over the drug supply in developing countries, driving the cost of drugs out of the range of affordability for the vast majority of the poor. One strategy to contain the cost of drugs is for governments to develop and implement an integrated national drug policy based upon the concept of essential drugs and their rational use. PMID:12292110

  16. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product...

  17. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product...

  18. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product...

  19. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product...

  20. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product...

  1. Simulation as an Aid to Experimental Design.

    ERIC Educational Resources Information Center

    Frazer, Jack W.; And Others

    1983-01-01

    Discusses simulation program to aid in the design of enzyme kinetic experimentation (includes sample runs). Concentration versus time profiles of any subset or all nine states of reactions can be displayed with/without simulated instrumental noise, allowing the user to estimate the practicality of any proposed experiment given known instrument…

  2. Computer Code Aids Design Of Wings

    NASA Technical Reports Server (NTRS)

    Carlson, Harry W.; Darden, Christine M.

    1993-01-01

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

  3. Computer-Aided Design in Further Education.

    ERIC Educational Resources Information Center

    Ingham, Peter, Ed.

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

  4. The Inter-Company Collaboration for AIDS Drug Development: boon or bust?

    PubMed

    Levin, J

    1995-06-01

    The Inter-Company Collaboration for AIDS Drug Development (ICC), formed in April 1993, is a consortium of international pharmaceutical companies that have agreed to conduct combination and comparative studies of antiviral agents for the treatment of HIV infection and AIDS. Members at the May 11, 1995 meeting discussed the start of the first triple-combination study of antiretroviral drugs conducted under the Collaboration's master multi-drug protocol. The trial (001) has been delayed by almost a year due to disagreement about its design. Protocol 001 will examine the antiviral and immunologic effects of two different three-drug combinations--AZT plus ddC plus saquinavir and AZT plus ddC plus nevirapine--and compare the three-drug combination to the two-drug combination of AZT plus ddC. Protocol 002 will compare the three-drug combination AZT plus ddI plus nevirapine to AZT plus ddI plus 3TC. These protocols, however, do not include the most promising new experimental treatments for HIV infection--the Merck and Abbott protease inhibitor drugs. The protocols use traditional study design. Researchers and activists are asking for uncontrolled, small, quick studies to screen new multi-drug combinations to discover the strongest possible antiviral effect as measured by polymerase chain reaction (PCR) and CD4 cell testing. Also vital to the AIDS community, is a clinical study combining two protease inhibitor drugs--Roche's saquinavir (Invirase) and Merck's indinavir sulfate (Crixivan).

  5. Design and use of improved walking aids.

    PubMed

    Nava, L C; Laura, P A

    1985-10-01

    The design of crutches and walking sticks to assist the disabled has not varied much since their original conception, some 5000 years ago. From an engineering viewpoint one must consider crutches and walking sticks as dynamic mechanical systems which alleviate a disability; they may act as supports, help the user to recover from stumbling, or transmit from the arms, the energy required to lift the feet from the ground, an action not provided by artificial ankle joints. We describe some dynamic walking aids recently developed at the Instituto de Mecánica Aplicada, and discuss their design and our experience with their use. They are adjustable in height, shock absorbing and have non-slipping tips. Specially developed aids have been designed for children; they are versatile and their use has been made psychologically attractive.

  6. 21 CFR 338.50 - Labeling of nighttime sleep-aid drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  7. 21 CFR 338.50 - Labeling of nighttime sleep-aid drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  8. 21 CFR 338.50 - Labeling of nighttime sleep-aid drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  9. 21 CFR 338.50 - Labeling of nighttime sleep-aid drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  10. 21 CFR 338.50 - Labeling of nighttime sleep-aid drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  11. Arthritis Genetics Analysis Aids Drug Discovery

    MedlinePlus

    ... biological insights for drug discovery,” Plenge says. —by Carol Torgan, Ph.D. Related Links Gut Microbes Linked ... Assistant Editors: Vicki Contie, Tianna Hicklin, Ph.D., Carol Torgan, Ph.D. NIH Research Matters is a ...

  12. Drug users' AIDS-related knowledge, attitudes, and behaviors before and after AIDS education sessions.

    PubMed Central

    Dengelegi, L; Weber, J; Torquato, S

    1990-01-01

    The investigators interviewed 100 drug users in a detoxification facility before and after they received information about acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV). The drug users already had a considerable amount of information about AIDS and HIV transmission modes before they received the information. However, 79 percent of them reported never having used condoms. Fifty percent of intravenous drug users acknowledged having shared needles during the previous year. Subjects exhibited psychological denial in appraising the riskiness of their personal sexual and needle-sharing behaviors, which they rated as less risky than those activities in general. Following their participation in an AIDS and HIV education program, their knowledge concerning modes of transmission and disease progression increased. Subjects became more aware of their personal risk for HIV infection, and their faith in condom effectiveness and their intent to use them increased. Intravenous drug users reported increased determination to stop their drug use. The results suggest that AIDS education efforts can be useful in programs to help prevent HIV transmission among drug users. PMID:2120728

  13. Geometric modeling for computer aided design

    NASA Technical Reports Server (NTRS)

    Schwing, James L.

    1992-01-01

    The goal was the design and implementation of software to be used in the conceptual design of aerospace vehicles. Several packages and design studies were completed, including two software tools currently used in the conceptual level design of aerospace vehicles. These tools are the Solid Modeling Aerospace Research Tool (SMART) and the Environment for Software Integration and Execution (EASIE). SMART provides conceptual designers with a rapid prototyping capability and additionally provides initial mass property analysis. EASIE provides a set of interactive utilities that simplify the task of building and executing computer aided design systems consisting of diverse, stand alone analysis codes that result in the streamlining of the exchange of data between programs, reducing errors and improving efficiency.

  14. ADAP faces financial abyss. AIDS Drug Assistance Programs.

    PubMed

    Link, D

    1996-02-01

    State AIDS Drug Assistance Programs (ADAPs) are the most heavily utilized AIDS programs in the nation, with over 50,000 people with HIV or AIDS enrolled. Initiated in 1987, the federally-funded programs are now running out of money because of increased caseloads and drug usage, higher drug costs, and more expensive combination therapies coupled with stagnant financial resources. Since 1990, the ADAPs have been funded by the Ryan White CARE Act, with each state administering its own ADAP, so eligibility criteria and formularies vary from state to state. Two states, Colorado and Missouri, have already run out of money and others have cut services, limited enrollment or canceled formulary expansions in the face of growing budget constraints. The National Association of State and Territorial AIDS Directors (NASTAD) surveyed state ADAPs and found that budget gaps ranged from $5.9 million in New York to $15,000 in Nebraska, and calculated that a total of $12 million would be needed just to make up the budget gaps for this fiscal year. The shortfall has led AIDS organizations to press for more funds at the state and Federal levels.

  15. Geometric modeling for computer aided design

    NASA Technical Reports Server (NTRS)

    Schwing, James L.

    1993-01-01

    Over the past several years, it has been the primary goal of this grant to design and implement software to be used in the conceptual design of aerospace vehicles. The work carried out under this grant was performed jointly with members of the Vehicle Analysis Branch (VAB) of NASA LaRC, Computer Sciences Corp., and Vigyan Corp. This has resulted in the development of several packages and design studies. Primary among these are the interactive geometric modeling tool, the Solid Modeling Aerospace Research Tool (smart), and the integration and execution tools provided by the Environment for Application Software Integration and Execution (EASIE). In addition, it is the purpose of the personnel of this grant to provide consultation in the areas of structural design, algorithm development, and software development and implementation, particularly in the areas of computer aided design, geometric surface representation, and parallel algorithms.

  16. Resident assistant training program for increasing alcohol, other drug, and mental health first-aid efforts.

    PubMed

    Thombs, Dennis L; Gonzalez, Jennifer M Reingle; Osborn, Cynthia J; Rossheim, Matthew E; Suzuki, Sumihiro

    2015-05-01

    In college and university residence halls, resident assistants (RAs) are expected to serve as first-aid providers to students who may have alcohol, other drug, mental health, and academic problems. Despite this responsibility, evidence-based, first-aid programs have not been developed and tested for the RA workforce. The current study examined effects of an investigational first-aid program designed specifically for RAs. The online Peer Hero Training program is a novel approach to RA training in its use of interactive video dramatizations of incidents involving substance-using or distressed residents. A 9-month randomized trial conducted on eight US campuses compared RAs who participated in the Peer Hero Training program to RAs who received training-as-usual. Participation in the Peer Hero Training program significantly increased RA first-aid efforts for residential students who may have had alcohol, other drug, mental health, or academic problems 6 months after baseline. Compared with those in the training-as-usual condition, RAs in the Peer Hero Training program made more than 10 times as many first-aid efforts for possible alcohol problems, almost 14 times the number of first-aid efforts for possible drug use, almost 3 times the number of first-aid efforts for possible mental health problems, and 3 times the number of first-aid efforts for academic problems. There was no evidence that measured RA attitudes mediated the effects of the intervention. Results of this preliminary evaluation trial suggest that online training using interactive video dramatizations is a viable approach to strengthening RAs' ability to provide alcohol, other drugs, and mental health first-aid to undergraduates.

  17. Resident Assistant Training Program for Increasing Alcohol, Other Drug, and Mental Health First-Aid Efforts

    PubMed Central

    Thombs, Dennis L.; Gonzalez, Jennifer M. Reingle; Osborn, Cynthia J.; Rossheim, Matthew E.; Suzuki, Sumihiro

    2014-01-01

    In college and university residence halls, resident assistants (RAs) are expected to serve as first-aid providers to students who may have alcohol, other drug, mental health, and academic problems. Despite this responsibility, evidence-based, first-aid programs have not been developed and tested for the RA workforce. The current study examined effects of an investigational first-aid program designed specifically for RAs. The online Peer Hero Training program is a novel approach to RA training in its use of interactive video dramatizations of incidents involving substance-using or distressed residents. A 9-month randomized trial conducted on 8 U.S. campuses compared RAs who participated in the Peer Hero Training program to RAs who received training-as-usual. Participation in the Peer Hero Training program significantly increased RA first-aid efforts for residential students who may have had alcohol, other drug, mental health, or academic problems six months after baseline. Compared to those in the training-as-usual condition, RAs in the Peer Hero Training program made more than 10 times as many first-aid efforts for possible alcohol problems, almost 14 times the number of first-aid efforts for possible drug use, almost 3 times the number of first-aid efforts for possible mental health problems, and 3 times the number of first-aid efforts for academic problems. There was no evidence that measured RA attitudes mediated the effects of the intervention. Results of this preliminary evaluation trial suggest that online training using interactive video dramatizations is a viable approach to strengthening RAs’ ability to provide alcohol, other drug, and mental health first-aid to undergraduates. PMID:25322950

  18. 21 CFR 344.52 - Labeling of ear drying aid drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of ear drying aid drug products. 344.52... Labeling of ear drying aid drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an “ear drying aid.”...

  19. 21 CFR 344.52 - Labeling of ear drying aid drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of ear drying aid drug products. 344.52... Labeling of ear drying aid drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an “ear drying aid.”...

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    Due to the time and effort requirements for the development of a new drug, and the high attrition rates associated with this developmental process, there is an intense effort by academic and industrial researchers to find novel ways for more effective drug development schemes. The first step in the discovery process of a new drug is the identification of the lead compound. The modern research tendency is to avoid the synthesis of new molecules based on chemical intuition, which is time and cost consuming, and instead to apply in silico rational drug design. This approach reduces the consumables and human personnel involved in the initial steps of the drug design. In this review real examples from our research activity aiming to discover new leads will be given for various dire warnings diseases. There is no recipe to follow for discovering new leads. The strategy to be followed depends on the knowledge of the studied system and the experience of the researchers. The described examples constitute successful and unsuccessful efforts and reflect the reality which medicinal chemists have to face in drug design and development. The drug stability is also discussed in both organic molecules and metallotherapeutics. This is an important issue in drug discovery as drug metabolism in the body can lead to various toxic and undesired molecules. PMID:25747445

  2. Geometric modeling for computer aided design

    NASA Technical Reports Server (NTRS)

    Schwing, James L.; Olariu, Stephen

    1995-01-01

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

  3. Domain specific software design for decision aiding

    NASA Technical Reports Server (NTRS)

    Keller, Kirby; Stanley, Kevin

    1992-01-01

    McDonnell Aircraft Company (MCAIR) is involved in many large multi-discipline design and development efforts of tactical aircraft. These involve a number of design disciplines that must be coordinated to produce an integrated design and a successful product. Our interpretation of a domain specific software design (DSSD) is that of a representation or framework that is specialized to support a limited problem domain. A DSSD is an abstract software design that is shaped by the problem characteristics. This parallels the theme of object-oriented analysis and design of letting the problem model directly drive the design. The DSSD concept extends the notion of software reusability to include representations or frameworks. It supports the entire software life cycle and specifically leads to improved prototyping capability, supports system integration, and promotes reuse of software designs and supporting frameworks. The example presented in this paper is the task network architecture or design which was developed for the MCAIR Pilot's Associate program. The task network concept supported both module development and system integration within the domain of operator decision aiding. It is presented as an instance where a software design exhibited many of the attributes associated with DSSD concept.

  4. Integrated computer-aided design using minicomputers

    NASA Technical Reports Server (NTRS)

    Storaasli, O. O.

    1980-01-01

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

  5. Aspects on Transfer of Aided - Design Files

    NASA Astrophysics Data System (ADS)

    Goanta, A. M.; Anghelache, D. G.

    2016-08-01

    At this stage of development of hardware and software, each company that makes design software packages has a certain type of file created and customized in time to distinguish that company from its competitors. Thus today are widely known the DWG files belonging AutoCAD, IPT / IAM belonging to Inventor, PAR / ASM of Solid Edge's, PRT from the NX and so on. Behind every type of file there is a mathematical model which is common to more types of files. A specific aspect of the computer -aided design is that all softwares are working with both individual parts and assemblies, but their approach is different in that some use the same type of file both for each part and for the whole (PRT ), while others use different types of files (IPT / IAM, PAR / ASM, etc.). Another aspect of the computer -aided design is to transfer files between different companies which use different software packages or even the same software package but in different versions. Each of these situations generates distinct issues. Thus, to solve the partial reading by a project different from the native one, transfer files of STEP and IGES type are used

  6. Computer-aided design of GPCR ligands.

    PubMed

    Gutiérrez-de-Terán, Hugo; Keränen, Henrik; Azuaje, Jhonny; Rodríguez, David; Åqvist, Johan; Sotelo, Eddy

    2015-01-01

    The recent availability of several GPCR crystal structures now contributes decisively to the perspective of structure-based ligand design. In this context, computational approaches are extremely helpful, particularly if properly integrated in drug design projects with cooperation between computational and medicinal chemistry teams. Here, we present the pipelines used in one such project, devoted to the design of novel potent and selective antagonists for the different adenosine receptors. The details of the computational strategies are described, and particular attention is given to explain how these procedures can effectively guide the synthesis of novel chemical entities.

  7. Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs

    PubMed Central

    Amon, Joseph J

    2008-01-01

    Background Increasing access to antiretroviral therapy (ART) is a critical goal endorsed by the United Nations and all of its member states. At the same time, anecdotal accounts suggest that the promotion of unproven AIDS 'cures' and remedies are widespread, and in the case of The Gambia, Iran and South Africa, have been promoted by governments directly. Although a range of legislative and regulatory measures have been adopted by some governments, and technical assistance has been provided by international agencies to address counterfeit medicines generally, the threat of counterfeit antiretroviral drugs is not being addressed. Discussion Countries, charged with fulfilling the right to health and committed to expanding access to ART must explicitly recognize their obligation to combat unproven AIDS treatments and ensure the availability of a safe and efficacious drugs supply. International donors must help support and coordinate these efforts. PMID:18304316

  8. International epidemiology of HIV and AIDS among injecting drug users.

    PubMed

    Des Jarlais, D C; Friedman, S R; Choopanya, K; Vanichseni, S; Ward, T P

    1992-10-01

    HIV/AIDS and iv drug use (IVDU) are of significant multinational scope and growing. Supporting increased IVDU in many countries are countries' geographical proximity to illicit drug trafficking distribution routes, law enforcement efforts which increase the demand for more efficient drug distribution and consumption, and countries' infrastructural and social modernization. Given the failures of intensified law enforcement efforts to thwart the use and proliferation of illegal drugs, countries with substantial IVDU should look away from preventing use to preventing HIV transmission within drug user populations. With HIV seroprevalence rates rapidly reaching 40-50% in some developing country IVDU groups, a variety of prevention programs is warranted. Such programs should be supported and implemented while prevention remains feasible. This paper examines the variation in HIV seroprevalence among IVD users, rapid HIV spread among users, HIV among IVDUs in Bangkok, emerging issues in HIV transmission among IVDUs, non-AIDS manifestations of HIV infection among IVDUs, prevention programs and effectiveness, and harm reduction. PMID:1466837

  9. Computer-aided software development process design

    NASA Technical Reports Server (NTRS)

    Lin, Chi Y.; Levary, Reuven R.

    1989-01-01

    The authors describe an intelligent tool designed to aid managers of software development projects in planning, managing, and controlling the development process of medium- to large-scale software projects. Its purpose is to reduce uncertainties in the budget, personnel, and schedule planning of software development projects. It is based on dynamic model for the software development and maintenance life-cycle process. This dynamic process is composed of a number of time-varying, interacting developmental phases, each characterized by its intended functions and requirements. System dynamics is used as a modeling methodology. The resulting Software LIfe-Cycle Simulator (SLICS) and the hybrid expert simulation system of which it is a subsystem are described.

  10. Drugs, Alcohol and HIV/AIDS: A Consumer Guide for African Americans

    MedlinePlus

    Drugs, Alcohol and HIV/AIDS A Consumer Guide Drugs & Alcohol What do drugs and alcohol have to do with HIV? Drug and alcohol use can ... behavior that can increase your exposure to HIV/AIDS. For example, using or sharing needles or other ...

  11. Computer-aided design and computer science technology

    NASA Technical Reports Server (NTRS)

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

    1976-01-01

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

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

    ERIC Educational Resources Information Center

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

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

  13. If we designed airplanes like we design drugs....

    PubMed

    Woltosz, Walter S

    2012-01-01

    In the early days, airplanes were put together with parts designed for other purposes (bicycles, farm equipment, textiles, automotive equipment, etc.). They were then flown by their brave designers to see if the design would work--often with disastrous results. Today, airplanes, helicopters, missiles, and rockets are designed in computers in a process that involves iterating through enormous numbers of designs before anything is made. Until very recently, novel drug-like molecules were nearly always made first like early airplanes, then tested to see if they were any good (although usually not on the brave scientists who created them!). The resulting extremely high failure rate is legendary. This article describes some of the evolution of computer-based design in the aerospace industry and compares it with the progress made to date in computer-aided drug design. Software development for pharmaceutical research has been largely entrepreneurial, with only relatively limited support from government and industry end-user organizations. The pharmaceutical industry is still about 30 years behind aerospace and other industries in fully recognizing the value of simulation and modeling and funding the development of the tools needed to catch up. PMID:22139474

  14. If we designed airplanes like we design drugs....

    PubMed

    Woltosz, Walter S

    2012-01-01

    In the early days, airplanes were put together with parts designed for other purposes (bicycles, farm equipment, textiles, automotive equipment, etc.). They were then flown by their brave designers to see if the design would work--often with disastrous results. Today, airplanes, helicopters, missiles, and rockets are designed in computers in a process that involves iterating through enormous numbers of designs before anything is made. Until very recently, novel drug-like molecules were nearly always made first like early airplanes, then tested to see if they were any good (although usually not on the brave scientists who created them!). The resulting extremely high failure rate is legendary. This article describes some of the evolution of computer-based design in the aerospace industry and compares it with the progress made to date in computer-aided drug design. Software development for pharmaceutical research has been largely entrepreneurial, with only relatively limited support from government and industry end-user organizations. The pharmaceutical industry is still about 30 years behind aerospace and other industries in fully recognizing the value of simulation and modeling and funding the development of the tools needed to catch up.

  15. Computer-aided design for metabolic engineering.

    PubMed

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

    2014-12-20

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

  16. Computer-aided design for metabolic engineering.

    PubMed

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

    2014-12-20

    The development and application of biotechnology-based strategies has had a great socio-economical impact and is likely to play a crucial role in the foundation of more sustainable and efficient industrial processes. Within biotechnology, metabolic engineering aims at the directed improvement of cellular properties, often with the goal of synthesizing a target chemical compound. The use of computer-aided design (CAD) tools, along with the continuously emerging advanced genetic engineering techniques have allowed metabolic engineering to broaden and streamline the process of heterologous compound-production. In this work, we review the CAD tools available for metabolic engineering with an emphasis, on retrosynthesis methodologies. Recent advances in genetic engineering strategies for pathway implementation and optimization are also reviewed as well as a range of bionalytical tools to validate in silico predictions. A case study applying retrosynthesis is presented as an experimental verification of the output from Retropath, the first complete automated computational pipeline applicable to metabolic engineering. Applying this CAD pipeline, together with genetic reassembly and optimization of culture conditions led to improved production of the plant flavonoid pinocembrin. Coupling CAD tools with advanced genetic engineering strategies and bioprocess optimization is crucial for enhanced product yields and will be of great value for the development of non-natural products through sustainable biotechnological processes. PMID:24704607

  17. The Adoption of Mental Health Drugs on State AIDS Drug Assistance Program Formularies

    PubMed Central

    Barry, Colleen L.

    2011-01-01

    Objectives. We sought state-level factors associated with the adoption of medications to treat mental health conditions on state formularies for the AIDS Drug Assistance Program. Methods. We interviewed 22 state and national program experts and identified 7 state-level factors: case burden, federal dollar-per-case Ryan White allocation size, political orientation, state wealth, passage of a mental health parity law, number of psychiatrists per population, and size of mental health budget. We then used survival analysis to test whether the factors were associated with faster adoption of psychotropic drugs from 1997 to 2008. Results. The relative size of a state's federal Ryan White HIV/AIDS Program allocation, the state's political orientation, and its concentration of psychiatrists were significantly associated with time-to-adoption of psychotropic drugs on state AIDS Drug Assistance Program formularies. Conclusions. Substantial heterogeneity exists across states in formulary adoption of drugs to treat mental illness. Understanding what factors contribute to variation in adoption is vital given the importance of treating mental health conditions as a component of comprehensive HIV care. PMID:21493949

  18. Software For Computer-Aided Design Of Control Systems

    NASA Technical Reports Server (NTRS)

    Wette, Matthew

    1994-01-01

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

  19. Issues of a Computer-Aided Design of Hydraulic Jacks

    NASA Astrophysics Data System (ADS)

    Averchenkov, V. I.; Averchenkov, A. V.; Kolyakinand, V. V.; Orekhov, O. D.

    2016-04-01

    The article deals with the issues of a computer-aided design of hydraulic equipment, namely hydraulic jacks. Design principles of the hydraulic jack CAD system are described. In addition, the possibilities for the system improvement and expansion are considered.

  20. COMPUTER-AIDED DRUG DISCOVERY AND DEVELOPMENT (CADDD): in silico-chemico-biological approach

    PubMed Central

    Kapetanovic, I.M.

    2008-01-01

    It is generally recognized that drug discovery and development are very time and resources consuming processes. There is an ever growing effort to apply computational power to the combined chemical and biological space in order to streamline drug discovery, design, development and optimization. In biomedical arena, computer-aided or in silico design is being utilized to expedite and facilitate hit identification, hit-to-lead selection, optimize the absorption, distribution, metabolism, excretion and toxicity profile and avoid safety issues. Commonly used computational approaches include ligand-based drug design (pharmacophore, a 3-D spatial arrangement of chemical features essential for biological activity), structure-based drug design (drug-target docking), and quantitative structure-activity and quantitative structure-property relationships. Regulatory agencies as well as pharmaceutical industry are actively involved in development of computational tools that will improve effectiveness and efficiency of drug discovery and development process, decrease use of animals, and increase predictability. It is expected that the power of CADDD will grow as the technology continues to evolve. PMID:17229415

  1. Structure-Based Strategies for Drug Design and Discovery

    NASA Astrophysics Data System (ADS)

    Kuntz, Irwin D.

    1992-08-01

    Most drugs have been discovered in random screens or by exploiting information about macromolecular receptors. One source of this information is in the structures of critical proteins and nucleic acids. The structure-based approach to design couples this information with specialized computer programs to propose novel enzyme inhibitors and other therapeutic agents. Iterated design cycles have produced compounds now in clinical trials. The combination of molecular structure determination and computation is emerging as an important tool for drug development. These ideas will be applied to acquired immunodeficiency syndrome (AIDS) and bacterial drug resistance.

  2. Bangkok 2004. Double discrimination: drug users living with HIV/AIDS.

    PubMed

    Samoilov, Dmitry

    2004-12-01

    Drug users in Russia living with HIV/AIDS are often denied basic medical and social services and are systematically excluded from antiretroviral therapy programs. In this presentation to "HIV Treatment for Drug Users--A Realistic Goal," a satellite meeting of the XIV International AIDS Conference held on 15 July 2004, Dmitry Samoilov describes the discrimination faced by people living with HIV/AIDS in general, and HIV-positive drug users in particular. The presentation includes powerful personal testimonials from people living with HIV/AIDS. The author describes the obstacles to drug users' accessing health care, and concludes with suggestions for actions that should be taken to address the problem.

  3. Bioanalysis of new designer drugs.

    PubMed

    Wohlfarth, Ariane; Weinmann, Wolfgang

    2010-05-01

    Since the late 1990s the illicit drug market has undergone considerable change: along with the traditional drugs of abuse that still dominate, more than 100 psychotropic substances designed to bypass controlled substances legislation have appeared and led to intoxications and fatalities. Starting from the huge class of phenylalkylamines, containing many subgroups, the spectrum of structures has grown from tryptamines, piperazines, phenylcyclohexyl derivates and pyrrolidinophenones to synthetic cannabinoids and the first synthetic cocaine. Due to the small prevalence and high number of unknown substances, the detection of new designer drugs is a challenge for clinical and forensic toxicologists. Standard screening procedures might fail because a recently discovered or yet unknown substance has not been incorporated in the library used. Nevertheless, many metabolism studies, case reports, screening methods and substance-profiling papers concentrating on single compounds have been published. This review provides an overview of the developed bioanalytical and analytical methods, the matrices used, sample-preparation procedures, concentration of analytes in case of intoxication and also gives a résumé of immunoassay experiences. Additionally, six screening methods for biological matrices with a larger spectrum of analytes are described in more detail.

  4. Computer-aided design development transition for IPAD environment

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

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

  5. PLAID- A COMPUTER AIDED DESIGN SYSTEM

    NASA Technical Reports Server (NTRS)

    Brown, J. W.

    1994-01-01

    PLAID is a three-dimensional Computer Aided Design (CAD) system which enables the user to interactively construct, manipulate, and display sets of highly complex geometric models. PLAID was initially developed by NASA to assist in the design of Space Shuttle crewstation panels, and the detection of payload object collisions. It has evolved into a more general program for convenient use in many engineering applications. Special effort was made to incorporate CAD techniques and features which minimize the users workload in designing and managing PLAID models. PLAID consists of three major modules: the Primitive Object Generator (BUILD), the Composite Object Generator (COG), and the DISPLAY Processor. The BUILD module provides a means of constructing simple geometric objects called primitives. The primitives are created from polygons which are defined either explicitly by vertex coordinates, or graphically by use of terminal crosshairs or a digitizer. Solid objects are constructed by combining, rotating, or translating the polygons. Corner rounding, hole punching, milling, and contouring are special features available in BUILD. The COG module hierarchically organizes and manipulates primitives and other previously defined COG objects to form complex assemblies. The composite object is constructed by applying transformations to simpler objects. The transformations which can be applied are scalings, rotations, and translations. These transformations may be defined explicitly or defined graphically using the interactive COG commands. The DISPLAY module enables the user to view COG assemblies from arbitrary viewpoints (inside or outside the object) both in wireframe and hidden line renderings. The PLAID projection of a three-dimensional object can be either orthographic or with perspective. A conflict analysis option enables detection of spatial conflicts or collisions. DISPLAY provides camera functions to simulate a view of the model through different lenses. Other

  6. Carbonic anhydrase inhibitors drug design.

    PubMed

    McKenna, Robert; Supuran, Claudiu T

    2014-01-01

    Inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) has pharmacologic applications in the field of antiglaucoma, anticonvulsant, antiobesity, and anticancer agents but is also emerging for designing anti-infectives (antifungal and antibacterial agents) with a novel mechanism of action. As a consequence, the drug design of CA inhibitors (CAIs) is a very dynamic field. Sulfonamides and their isosteres (sulfamates/sulfamides) constitute the main class of CAIs which bind to the metal ion in the enzyme active site. Recently the dithiocarbamates, possessing a similar mechanism of action, were reported as a new class of inhibitors. Other families of CAIs possess a distinct mechanism of action: phenols, polyamines, some carboxylates, and sulfocoumarins anchor to the zinc-coordinated water molecule. Coumarins and five/six-membered lactones are prodrug inhibitors, binding in hydrolyzed form at the entrance of the active site cavity. Novel drug design strategies have been reported principally based on the tail approach for obtaining all these types of CAIs, which exploit more external binding regions within the enzyme active site (in addition to coordination to the metal ion), leading thus to isoform-selective compounds. Sugar-based tails as well as click chemistry were the most fruitful developments of the tail approach. Promising compounds that inhibit CAs from bacterial and fungal pathogens, of the dithiocarbamate, phenol and carboxylate types have also been reported. PMID:24146385

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

    PubMed

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

    2016-09-01

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multiscale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multiscale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical and computational techniques employed for multiscale modeling approaches used in pharmacometric and systems pharmacology models in drug development and present several examples illustrating the current state-of-the-art models for (1) excitable systems and applications in cardiac disease; (2) stem cell driven complex biosystems; (3) nanoparticle delivery, with applications to angiogenesis and cancer therapy; (4) host-pathogen interactions and their use in metabolic disorders, inflammation and sepsis; and (5) computer-aided design of nanomedical systems. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multiscale models. PMID:26885640

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

    PubMed

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

    2016-09-01

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multiscale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multiscale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical and computational techniques employed for multiscale modeling approaches used in pharmacometric and systems pharmacology models in drug development and present several examples illustrating the current state-of-the-art models for (1) excitable systems and applications in cardiac disease; (2) stem cell driven complex biosystems; (3) nanoparticle delivery, with applications to angiogenesis and cancer therapy; (4) host-pathogen interactions and their use in metabolic disorders, inflammation and sepsis; and (5) computer-aided design of nanomedical systems. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multiscale models.

  9. Stigmatization of AIDS patients: disentangling Thai nursing students' attitudes towards HIV/AIDS, drug use, and commercial sex.

    PubMed

    Chan, Kit Yee; Stoové, Mark A; Sringernyuang, Luechai; Reidpath, Daniel D

    2008-01-01

    This paper analyzes the interrelationships between the stigma of HIV/AIDS stigma and the co-stigmas of commercial sex (CS) and injecting drug use (IDU). Students of a Bangkok nursing college (N=144) were presented with vignettes describing a person varying in the disease diagnoses (AIDS, leukemia, no disease) and co-characteristics (IDU, CS, blood transfusion, no co-characteristic). For each vignette, participants completed a social distance measure assessing their attitudes towards the hypothetical person portrayed. Multivariate analyses showed strong interactions between the stigmas of AIDS and IDU but not between AIDS and CS. Although AIDS was shown to be stigmatizing in and of itself, it was significantly less stigmatizing than IDU. The findings highlight the need to consider the non-disease-related stigmas associated with HIV as well as the actual stigma of HIV/AIDS in treatment and care settings. Methodological strengths and limitations were evaluated and implications for future research discussed.

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

    ERIC Educational Resources Information Center

    Fitzpatrick, F. J.; And Others

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

  11. Fragment-based drug design.

    PubMed

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

    2011-01-01

    Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process. PMID:20981527

  12. Artwork Interactive Design System (AIDS) program description

    NASA Technical Reports Server (NTRS)

    Johnson, B. T.; Taylor, J. F.

    1976-01-01

    An artwork interactive design system is described which provides the microelectronic circuit designer/engineer a tool to perform circuit design, automatic layout modification, standard cell design, and artwork verification at a graphics computer terminal using a graphics tablet at the designer/computer interface.

  13. Computer-aided dispatching system design specification

    SciTech Connect

    Briggs, M.G.

    1997-12-16

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

  14. School District Uses Computer Aided Design and Drafting.

    ERIC Educational Resources Information Center

    Lorentz, Gordon S.

    1988-01-01

    Computer Aided Design and Drafting (CADD) programs are used to teach drafting at an Indiana high school. The school system's maintenance department shared use of the software and equipment to produce original drawings of school buildings. (MLF)

  15. TOMOCOMD-CARDD, a novel approach for computer-aided 'rational' drug design: I. Theoretical and experimental assessment of a promising method for computational screening and in silico design of new anthelmintic compounds.

    PubMed

    Marrero-Ponce, Yovani; Castillo-Garit, Juan A; Olazabal, Ervelio; Serrano, Hector S; Morales, Alcidez; Castañedo, Nilo; Ibarra-Velarde, Froylán; Huesca-Guillen, Alma; Jorge, Elisa; del Valle, Arletys; Torrens, Francisco; Castro, Eduardo A

    2004-10-01

    In this work, the TOMOCOMD-CARDD approach has been applied to estimate the anthelmintic activity. Total and local (both atom and atom-type) quadratic indices and linear discriminant analysis were used to obtain a quantitative model that discriminates between anthelmintic and non-anthelmintic drug-like compounds. The obtained model correctly classified 90.37% of compounds in the training set. External validation processes to assess the robustness and predictive power of the obtained model were carried out. The QSAR model correctly classified 88.18% of compounds in this external prediction set. A second model was performed to outline some conclusions about the possible modes of action of anthelmintic drugs. This model permits the correct classification of 94.52% of compounds in the training set, and 80.00% of good global classification in the external prediction set. After that, the developed model was used in virtual in silico screening and several compounds from the Merck Index, Negwer's handbook and Goodman and Gilman were identified by models as anthelmintic. Finally, the experimental assay of one organic chemical (G-1) by an in vivo test coincides fairly well (100%) with model predictions. These results suggest that the proposed method will be a good tool for studying the biological properties of drug candidates during the early state of the drug-development process.

  16. The incidence and spectrum of AIDS-defining illnesses in persons treated with antiretroviral drugs.

    PubMed

    Forrest, D M; Seminari, E; Hogg, R S; Yip, B; Raboud, J; Lawson, L; Phillips, P; Schechter, M T; O'Shaughnessy, M V; Montaner, J S

    1998-12-01

    The incidence and spectrum of primary AIDS-defining illnesses in human immunodeficiency virus-positive patients receiving antiretroviral drugs may have changed since the introduction of newer antiretroviral agents. We performed a retrospective analysis of patients enrolled in the British Columbia Drug Treatment Program who were ever prescribed antiretroviral drugs between 1 January 1994 and 31 December 1996. Rates were calculated on a 6-month basis. There were 344 AIDS cases diagnosed among 2,533 participants between 1994 and 1996. The incidence of primary AIDS diseases decreased from 1994 to 1996, with a sharp decline in 1995 and 1996. There was no statistically significant change in the incidence of primary AIDS diagnoses relative to one another, and Pneumocystis carinii pneumonia and Kaposi's sarcoma remain the most common AIDS index diagnoses. In patients receiving antiretroviral therapy in the modern era, the incidence of AIDS-defining illnesses has decreased substantially, but the spectrum of AIDS-defining illnesses remains unchanged.

  17. Opiate drug use and the pathophysiology of neuroAIDS.

    PubMed

    Hauser, Kurt F; Fitting, Sylvia; Dever, Seth M; Podhaizer, Elizabeth M; Knapp, Pamela E

    2012-07-01

    Opiate abuse and HIV-1 have been described as interrelated epidemics, and even in the advent of combined anti-retroviral therapy, the additional abuse of opiates appears to result in greater neurologic and cognitive deficits. The central nervous system (CNS) is particularly vulnerable to interactive opiate-HIV-1 effects, in part because of the unique responses of microglia and astroglia. Although neurons are principally responsible for behavior and cognition, HIV-1 infection and replication in the brain is largely limited to microglia, while astroglia and perhaps glial progenitors can be latently infected. Thus, neuronal dysfunction and injury result from cellular and viral toxins originating from HIV-1 infected/exposed glia. Importantly, subsets of glial cells including oligodendrocytes, as well as neurons, express µ-opioid receptors and therefore can be direct targets for heroin and morphine (the major metabolite of heroin in the CNS), which preferentially activate µ-opioid receptors. This review highlights findings that neuroAIDS is a glially driven disease, and that opiate abuse may act at multiple glial-cell types to further compromise neuron function and survival. The ongoing, reactive cross-talk between opiate drug and HIV-1 co-exposed microglia and astroglia appears to exacerbate critical proinflammatory and excitotoxic events leading to neuron dysfunction, injury, and potentially death. Opiates enhance synaptodendritic damage and a loss of synaptic connectivity, which is viewed as the substrate of cognitive deficits. We especially emphasize that opioid signaling and interactions with HIV-1 are contextual, differing among cell types, and even within subsets of the same cell type. For example, astroglia even within a single brain region are heterogeneous in their expression of µ-, δ-, and κ-opioid receptors, as well as CXCR4 and CCR5, and Toll-like receptors. Thus, defining the distinct targets engaged by opiates in each cell type, and among brain

  18. Molecular Similarity in Computer-Aided Molecular Design.

    NASA Astrophysics Data System (ADS)

    Hodgkin, Edward E.

    Available from UMI in association with The British Library. Requires signed TDF. The quantitative measurement of how similar one molecule is to another is investigated as a potential aid to molecular design. The work concentrates on the comparison of electronic properties of molecules, in particular electron density distribution, molecular electrostatic potential, molecular electric field and frontier orbital wavefunctions. A novel formula for molecular similarity has been devised and applied to these four properties. An approximate representation of valence electron density is used, based on the notion that charge distribution in a large molecule may be built from transferable contributions from its constituent functional groups. Each of these contributions consists of a series of first-order gaussian functions. The electrostatic potentials and electric fields used in the similarity calculations are computed from atom -centered partial charges. The frontier orbital wavefunction comparisons are performed using the extended Huckel method. The four measures of similarity are related to chemical and biological data and shown to have possible applications in the area of drug design.

  19. The chemical bases of the various AIDS epidemics: recreational drugs, anti-viral chemotherapy and malnutrition.

    PubMed

    Duesberg, Peter; Koehnlein, Claus; Rasnick, David

    2003-06-01

    In 1981 a new epidemic of about two-dozen heterogeneous diseases began to strike non-randomly growing numbers of male homosexuals and mostly male intravenous drug users in the US and Europe. Assuming immunodeficiency as the common denominator the US Centers for Disease Control (CDC) termed the epidemic, AIDS, for acquired immunodeficiency syndrome. From 1981-1984 leading researchers including those from the CDC proposed that recreational drug use was the cause of AIDS, because of exact correlations and of drug-specific diseases. However, in 1984 US government researchers proposed that a virus, now termed human immunodeficiency virus (HIV), is the cause of the non-random epidemics of the US and Europe but also of a new, sexually random epidemic in Africa. The virus-AIDS hypothesis was instantly accepted, but it is burdened with numerous paradoxes, none of which could be resolved by 2003: Why is there no HIV in most AIDS patients, only antibodies against it? Why would HIV take 10 years from infection to AIDS? Why is AIDS not self-limiting via antiviral immunity? Why is there no vaccine against AIDS? Why is AIDS in the US and Europe not random like other viral epidemics? Why did AIDS not rise and then decline exponentially owing to antiviral immunity like all other viral epidemics? Why is AIDS not contagious? Why would only HIV carriers get AIDS who use either recreational or anti-HIV drugs or are subject to malnutrition? Why is the mortality of HIV-antibody-positives treated with anti-HIV drugs 7-9%, but that of all (mostly untreated) HIV-positives globally is only 1.4%? Here we propose that AIDS is a collection of chemical epidemics, caused by recreational drugs, anti-HIV drugs, and malnutrition. According to this hypothesis AIDS is not contagious, not immunogenic, not treatable by vaccines or antiviral drugs, and HIV is just a passenger virus. The hypothesis explains why AIDS epidemics strike non-randomly if caused by drugs and randomly if caused by malnutrition

  20. An experiential program to reduce AIDS risk among female sex partners of injection-drug users.

    PubMed

    Rhodes, F; Wolitski, R J; Thornton-Johnson, S

    1992-11-01

    This article describes the development and implementation of an acquired immune deficiency syndrome (AIDS) intervention program for female sex partners of male injection-drug users. Four psychoeducational workshops were designed to motivate personal risk reduction, provide participants with necessary cognitive and behavioral skills, and enhance participants' perceived ability to enact positive changes in their lives. The development of the workshop modules was guided by traditional theories of health behavior change and social learning. Also included in the intervention are referral and advocacy services, personal risk reduction counseling, and human immunodeficiency virus (HIV) antibody testing. Preliminary results indicate that the program has made a significant impact on the AIDS risk of participants--91 percent of women who completed the program reported that they had made positive changes in their lives to reduce their risk of HIV infection.

  1. Improving Outcomes in State AIDS Drug Assistance Programs

    PubMed Central

    Linas, Benjamin P.; Losina, Elena; Rockwell, Annette; Walensky, Rochelle P.; Cranston, Kevin; Freedberg, Kenneth A.

    2009-01-01

    Background State AIDS Drug Assistance Programs (ADAPs) provide antiretroviral medications to patients with no access to medications. Resource constraints limit many ADAPs' ability to meet demand for services. Objective To determine ADAP eligibility criteria that minimize morbidity and mortality and contain costs. Methods We used Discrete Event Simulation to model the progression of HIV-infected patients and track utilization of an ADAP. Outcomes included five-year mortality and incidence of first opportunistic infection or death, and time to starting ART. We compared expected outcomes for two policies: 1) first-come, first-served (FCFS) eligibility for all with CD4 count ≤350/μl (current standard), and 2) CD4 count prioritized eligibility for those with CD4 counts below a defined threshold. Results In the base case, prioritizing patients with CD4 counts ≤250/μl led to lower five-year mortality than FCFS eligibility [2.77 vs. 3.27 deaths/1,000 person months], and to a lower incidence of first opportunistic infection or death [5.55 vs. 6.98 events/1,000 person months]. CD4-based eligibility reduced the time to starting ART for patients with CD4 counts ≤200/μl. In sensitivity analyses, CD4-based eligibility consistently led to lower morbidity and mortality than FCFS eligibility. Conclusions When resources are limited, programs that provide ART can improve outcomes by prioritizing patients with low CD4 counts. PMID:19561518

  2. Interactive graphical computer-aided design system

    NASA Technical Reports Server (NTRS)

    Edge, T. M.

    1975-01-01

    System is used for design, layout, and modification of large-scale-integrated (LSI) metal-oxide semiconductor (MOS) arrays. System is structured around small computer which provides real-time support for graphics storage display unit with keyboard, slave display unit, hard copy unit, and graphics tablet for designer/computer interface.

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

    PubMed Central

    2014-01-01

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

  4. Human factors of intelligent computer aided display design

    NASA Technical Reports Server (NTRS)

    Hunt, R. M.

    1985-01-01

    Design concepts for a decision support system being studied at NASA Langley as an aid to visual display unit (VDU) designers are described. Ideally, human factors should be taken into account by VDU designers. In reality, although the human factors database on VDUs is small, such systems must be constantly developed. Human factors are therefore a secondary consideration. An expert system will thus serve mainly in an advisory capacity. Functions can include facilitating the design process by shortening the time to generate and alter drawings, enhancing the capability of breaking design requirements down into simpler functions, and providing visual displays equivalent to the final product. The VDU system could also discriminate, and display the difference, between designer decisions and machine inferences. The system could also aid in analyzing the effects of designer choices on future options and in ennunciating when there are data available on a design selections.

  5. Program Aids Analysis And Optimization Of Design

    NASA Technical Reports Server (NTRS)

    Rogers, James L., Jr.; Lamarsh, William J., II

    1994-01-01

    NETS/ PROSSS (NETS Coupled With Programming System for Structural Synthesis) computer program developed to provide system for combining NETS (MSC-21588), neural-network application program and CONMIN (Constrained Function Minimization, ARC-10836), optimization program. Enables user to reach nearly optimal design. Design then used as starting point in normal optimization process, possibly enabling user to converge to optimal solution in significantly fewer iterations. NEWT/PROSSS written in C language and FORTRAN 77.

  6. Drugs for all: the future of global AIDS treatment.

    PubMed

    Biehl, João

    2008-01-01

    I am interested in the arts of government that accompany economic globalization and in the remaking of populations as market segments (specifically therapeutic markets). Using the Brazilian response to AIDS as an ethnographic baseline, I examine the systemic relations between pharmaceutical commerce and public health care and the value systems that underscore global AIDS treatment initiatives. The pharmaceuticalization of governance and citizenship, obviously efficacious in the treatment of AIDS, nonetheless crystallizes new inequalities.

  7. [Nicotine--drug addiction--AIDS. Drug use habits of Vienna addicts].

    PubMed

    Loimer, N; Vedovelli, H; Presslich, O; Werner, E; Hollerer, E; Pfersmann, V; Schmid-Siegel, B

    1991-01-01

    In Austria it is illegal to sell tobacco to young adolescents. A diverse sample of 358 narcotic addicts was investigated at the Psychiatric University Clinic of Vienna. Data were obtained from on site confidential interviews and a HIV-test was conducted. The individual drug use history was recorded and, interestingly, tobacco addiction was the first stage in starting a drug career. Furthermore, a strong correlation was observed between onset of heroin use and HIV-1 infection. It is concluded that in Austria not only the availability nicotine and alcohol to young adolescents should be prohibited, but also their use should be punishable. Easy access to nicotine as in public restaurants or from automatic distributors, has to be withdrawn. Tobacco advertisements may drive vulnerable young adolescents to early nicotine abuse and this may be followed by addition to other drugs and diseases causing death, including AIDS. Socioeconomic data, as well as the methadone data are presented. 180 out of the 358 patients were on methadone maintenance. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society. Physicians have a clear responsibility to lead the effort on all fronts against tobacco, especially in view of the HIV epidemic. PMID:1763508

  8. Memory interface simulator: A computer design aid

    NASA Technical Reports Server (NTRS)

    Taylor, D. S.; Williams, T.; Weatherbee, J. E.

    1972-01-01

    Results are presented of a study conducted with a digital simulation model being used in the design of the Automatically Reconfigurable Modular Multiprocessor System (ARMMS), a candidate computer system for future manned and unmanned space missions. The model simulates the activity involved as instructions are fetched from random access memory for execution in one of the system central processing units. A series of model runs measured instruction execution time under various assumptions pertaining to the CPU's and the interface between the CPU's and RAM. Design tradeoffs are presented in the following areas: Bus widths, CPU microprogram read only memory cycle time, multiple instruction fetch, and instruction mix.

  9. Computer aided design study of hypermixing nozzles

    NASA Technical Reports Server (NTRS)

    Mefferd, L. A.; Bevilacqua, P. M.

    1979-01-01

    The development of a nozzle which combines the hypermixing and lobe mechanisms to achieve further increases in jet entrainment and ejector performance is investigated. A computer program which incorporates a two equation turbulence model and is used to predict and compare the evolution of jets from various nozzle designs is discussed. Increasing the length of the nozzle lobes and an alternating lobe nozzle are a methods examined for increasing the entrainment rate.

  10. Luminance in computer-aided lighting design

    SciTech Connect

    Ward, G.J.; Rubinstein, F.M.; Grynberg, A.

    1987-08-01

    Traditionally, the lighting engineering community has emphasized illuminance, the amount of light reaching a surface, as the primary design goal. The Illuminating Engineering Society (IES) provides tables of illuminances for different types of tasks which lighting engineers consult in designing lighting systems. Illuminance has proven to be a popular metric because it corresponds closely to the amount of energy needed to light a building as well as the initial cost of the lighting system. Perhaps more importantly, illuminance is easy to calculate, especially in simple unobstructed spaces with direct lighting. However,illuminance is not well correlated with visual performance, which is the real reason for installing a lighting system in the first place. Visual performance is a psychophysiological quantity that has been tied to physical quantities such as contrast, size and adaptation level by subject experiments. These physical quantities can be approximated from illuminance using a host of assumptions about the environment, or derived directly from the distribution of luminance. Luminance is the quantity of light traveling through a point in a certain direction, and it is this quantity that the eye actually sees''. However, the difficulty of calculating luminance for common tasks has made it an unpopular metric. Despite its importance to lighting design, luminance is rarely used because there is a lack of the necessary computational tools.In this paper, we will demonstrate a computer calculation of luminance that has significant advantages for lighting design. As well as providing an immediate evaluation of visual quality for task performance, less quantifiable factors such as aesthetics can be studied in synthetic images produced by the program.

  11. Luminance in computer-aided lighting design

    SciTech Connect

    Ward, G.J.; Rubinstein, F.M.; Grynberg, A.

    1987-08-01

    Traditionally, the lighting engineering community has emphasized illuminance, the amount of light reaching a surface, as the primary design goal. The Illuminating Engineering Society (IES) provides tables of illuminances for different types of tasks which lighting engineers consult in designing lighting systems. Illuminance has proven to be a popular metric because it corresponds closely to the amount of energy needed to light a building as well as the initial cost of the lighting system. Perhaps more importantly, illuminance is easy to calculate, especially in simple unobstructed spaces with direct lighting. However,illuminance is not well correlated with visual performance, which is the real reason for installing a lighting system in the first place. Visual performance is a psychophysiological quantity that has been tied to physical quantities such as contrast, size and adaptation level by subject experiments. These physical quantities can be approximated from illuminance using a host of assumptions about the environment, or derived directly from the distribution of luminance. Luminance is the quantity of light traveling through a point in a certain direction, and it is this quantity that the eye actually ``sees``. However, the difficulty of calculating luminance for common tasks has made it an unpopular metric. Despite its importance to lighting design, luminance is rarely used because there is a lack of the necessary computational tools.In this paper, we will demonstrate a computer calculation of luminance that has significant advantages for lighting design. As well as providing an immediate evaluation of visual quality for task performance, less quantifiable factors such as aesthetics can be studied in synthetic images produced by the program.

  12. Computer-Aided Design Of Sheet-Material Parts

    NASA Technical Reports Server (NTRS)

    Gilbert, Jeffrey L.; Paternoster, Vincent Y.; Levitt, Maureen L.; Osterloh, Mark R.

    1991-01-01

    Computer-aided-design system partly automates tedious process of designing and guiding assembly of small pieces of flat sheet material into large surfaces that approximate smoothly curved surfaces having complicated three-dimensional shapes. Capability provides for flexibility enabling designer to assess quickly and easily effects of changes in design in making engineering compromises among various sizes and shapes. Saves time and money in both design and fabrication. Used in rocket-engine application and other applications requiring design of sheet-material parts.

  13. Participatory design for drug-drug interaction alerts.

    PubMed

    Luna, Daniel; Otero, Carlos; Almerares, Alfredo; Stanziola, Enrique; Risk, Marcelo; González Bernaldo de Quirós, Fernán

    2015-01-01

    The utilization of decision support systems, in the point of care, to alert drug-drug interactions has been shown to improve quality of care. Still, the use of these systems has not been as expected, it is believed, because of the difficulties in their knowledge databases; errors in the generation of the alerts and the lack of a suitable design. This study expands on the development of alerts using participatory design techniques based on user centered design process. This work was undertaken in three stages (inquiry, participatory design and usability testing) it showed that the use of these techniques improves satisfaction, effectiveness and efficiency in an alert system for drug-drug interactions, a fact that was evident in specific situations such as the decrease of errors to meet the specified task, the time, the workload optimization and users overall satisfaction in the system.

  14. Participatory design for drug-drug interaction alerts.

    PubMed

    Luna, Daniel; Otero, Carlos; Almerares, Alfredo; Stanziola, Enrique; Risk, Marcelo; González Bernaldo de Quirós, Fernán

    2015-01-01

    The utilization of decision support systems, in the point of care, to alert drug-drug interactions has been shown to improve quality of care. Still, the use of these systems has not been as expected, it is believed, because of the difficulties in their knowledge databases; errors in the generation of the alerts and the lack of a suitable design. This study expands on the development of alerts using participatory design techniques based on user centered design process. This work was undertaken in three stages (inquiry, participatory design and usability testing) it showed that the use of these techniques improves satisfaction, effectiveness and efficiency in an alert system for drug-drug interactions, a fact that was evident in specific situations such as the decrease of errors to meet the specified task, the time, the workload optimization and users overall satisfaction in the system. PMID:25991099

  15. Bangkok 2004. Drug control, human rights, and harm reduction in the age of AIDS.

    PubMed

    Elliott, Richard

    2004-12-01

    In many countries, HIV prevalence among people who use illicit drugs is high. Yet many governments resist implementing effective HIV prevention measures, and drug users often lack access to care, treatment, and support, including for HIV/AIDS. Growing evidence indicates the dominant prohibitionist approach to illicit drugs is ineffective--and even counterproductive, blocking or undermining measures shown to reduce harms to drug users and to communities affected by open drug scenes. The growing debate over global drug control policy could shift us collectively away from the current, failed prescriptions to a more rational, pragmatic, and health-promoting framework of harm reduction. This article by Richard Elliott is an abridged version of a paper prepared for "Human Rights at the Margins: HIV/AIDS, Prisoners, Drug Users and the Law," a satellite meeting held in Bangkok on 9 July 2004, and organized by the Canadian HIV/AIDS Legal Network and the Lawyers Collective HIV/AIDS Unit (India). The article briefly outlines the impact of these two different policy approaches, examines international law on drug control, discusses how harm reduction reflects a human rights-based approach to drugs, and assesses some strategies for reforming global policy on illicit drugs. PMID:15812929

  16. Clinical analysis of HIV/AIDS patients with drug eruption in Yunnan, China

    PubMed Central

    Li, Yu-Ye; Jin, Yong-Mei; He, Li-Ping; Bai, Jin-Song; Liu, Jun; Yu, Min; Chen, Jian-Hua; Wen, Jing; Kuang, Yi-Qun

    2016-01-01

    Drug eruption is the most common clinical presentation in patients with HIV/AIDS. The systemic clinical and risk factors associated with drug eruption remain unknown. A retrospective analysis in HIV/AIDS patients with drug eruption was carried out with demographic data, epidemiological data, clinical characteristics, laboratory data and follow-up data. The risk factors correlated with prognosis were assessed by case control analysis. A total of 134 out of 1817 HIV/AIDS patients (7.4%) presented drug eruptions. The major class of sensitizing drug was HAART drugs (47.7%), followed by antibiotics (47.0%). Nevirapine (39.6%) was the most common sensitizing drug in the HAART regimens. The patients received HAART or had allergic history were prone to develop drug eruption. The alanine aminotransferase, albumin, globulin, creatinine, blood urea nitrogen (BUN), lymphocytes, red blood cells (RBC) and eosinophils of the drug eruption patients were significantly different the control patients. The allergic history, opportunistic infection, viral load, CD4 cell count, high globulin and low albumin were the risk factors correlated with death in HIV/AIDS patients with drug eruption. It is proposed that patients with higher viral loads, higher globulin levels and lower white blood cells (WBC) should be given special attention for the prevention of complications and death. PMID:27796328

  17. National Occupational Skill Standards. CADD: Computer Aided Drafting and Design.

    ERIC Educational Resources Information Center

    National Coalition for Advanced Manufacturing, Washington, DC.

    This document identifies computer-aided drafting and design (CADD) skills that companies require of training programs and future employees. The information was developed by two committees of technically knowledgeable CADD users from across the United States and validated by several hundred other CADD users. The skills are aimed at a beginner CADD…

  18. Information technology aided exploration of system design spaces

    NASA Technical Reports Server (NTRS)

    Feather, Martin S.; Kiper, James D.; Kalafat, Selcuk

    2004-01-01

    We report on a practical application of information technology techniques to aid system engineers effectively explore large design spaces. We make use of heuristic search, visualization and data mining, the combination of which we have implemented wtihin a risk management tool in use at JPL and NASA.

  19. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Timing of requests for orphan-drug designation..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.23 Timing of requests for orphan-drug designation; designation of already approved drugs....

  20. Computer-aided design of flight control systems

    NASA Technical Reports Server (NTRS)

    Stengel, Robert F.; Sircar, Subrata

    1991-01-01

    A computer program is presented for facilitating the development and assessment of flight control systems, and application to a control design is discussed. The program is a computer-aided control-system design program based on direct digital synthesis of a proportional-integral-filter controller with scheduled linear-quadratic-Gaussian gains and command generator tracking of pilot inputs. The FlightCAD system concentrates on aircraft dynamics, flight-control systems, stability and performance, and has practical engineering applications.

  1. SNL Mechanical Computer Aided Design (MCAD) guide 2007.

    SciTech Connect

    Moore, Brandon; Pollice, Stephanie L.; Martinez, Jack R.

    2007-12-01

    This document is considered a mechanical design best-practice guide to new and experienced designers alike. The contents consist of topics related to using Computer Aided Design (CAD) software, performing basic analyses, and using configuration management. The details specific to a particular topic have been leveraged against existing Product Realization Standard (PRS) and Technical Business Practice (TBP) requirements while maintaining alignment with sound engineering and design practices. This document is to be considered dynamic in that subsequent updates will be reflected in the main title, and each update will be published on an annual basis.

  2. 21 CFR 316.24 - Granting orphan-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Granting orphan-drug designation. 316.24 Section 316.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.24 Granting orphan-drug...

  3. 21 CFR 316.24 - Granting orphan-drug designation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Granting orphan-drug designation. 316.24 Section 316.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.24 Granting orphan-drug...

  4. 21 CFR 316.24 - Granting orphan-drug designation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Granting orphan-drug designation. 316.24 Section 316.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.24 Granting orphan-drug...

  5. 21 CFR 316.24 - Granting orphan-drug designation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Granting orphan-drug designation. 316.24 Section 316.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.24 Granting orphan-drug...

  6. Confronting the AIDS epidemic among i.v. drug users: does ethnic culture matter?

    PubMed

    Singer, M

    1991-01-01

    The AIDS education and prevention literature contains numerous calls for the development of culturally relevant efforts to reach members of ethnic minority populations. In the AIDS literature on IV drug users (IVDUs), however, this issue finds less emphasis despite the disproportionate rate of human immunodeficiency virus (HIV) infection in minority IVDUs. The reason appears to be the sense in the drug field that the primary culture of the IVDU is drug culture rather than ethnic culture. This paper explores this issue in light of a review of recent research on IVDUs, ethnicity, and AIDS risk behavior. Specifically, this review covers literature on 6 topics in light of ethnic differences: changing patterns of IV drug use prevalence, AIDS prevalence among IVDUs, needle-related AIDS risk, polydrug use, sexual risk among IVDUs, and the drug subculture. Finding that ethnic culture does matter in infection patterns and risk behavior, this paper examines a typology for the analysis of discontinuities in intercultural communication and presents a framework for comparing alternative models for overcoming cultural barriers to effective AIDS education with IVDUs. PMID:1931428

  7. Thermodynamic Studies for Drug Design and Screening

    PubMed Central

    Garbett, Nichola C.; Chaires, Jonathan B.

    2012-01-01

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

  8. NanoART, neuroAIDS and CNS drug delivery

    PubMed Central

    Nowacek, Ari; Gendelman, Howard E

    2009-01-01

    A broad range of nanomedicines is being developed to improve drug delivery for CNS disorders. The structure of the blood–brain barrier (BBB), the presence of efflux pumps and the expression of metabolic enzymes pose hurdles for drug-brain entry. Nanoformulations can circumvent the BBB to improve CNS-directed drug delivery by affecting such pumps and enzymes. Alternatively, they can be optimized to affect their size, shape, and protein and lipid coatings to facilitate drug uptake, release and ingress across the barrier. This is important as the brain is a sanctuary for a broad range of pathogens including HIV-1. Improved drug delivery to the CNS would affect pharmacokinetic and drug biodistribution properties. This article focuses on how nanotechnology can serve to improve the delivery of antiretroviral medicines, termed nanoART, across the BBB and affect the biodistribution and clinical benefit for HIV-1 disease. PMID:19572821

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

    PubMed Central

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

    2013-01-01

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

  10. The Save-Your-Life Glossary of Alcohol, AIDS, Drug, & Tobacco Terms.

    ERIC Educational Resources Information Center

    Adcock, Deborah

    This document presents the Save-Your-Life Glossary, which consists of four parts: (1) the glossary itself, which defines alcohol, Acquired Immune Deficiency Syndrome (AIDS), drug, and tobacco-related terms; (2) the alerts sections, which focus on popular drugs or issues that concern young people; (3) the focus sections, which categorize and…

  11. AIDS and Intravenous Drug Use: A Growing Menace.

    ERIC Educational Resources Information Center

    Zapata, Vicente; Blanton, Carlton

    1994-01-01

    Needle sharing by intravenous drug users has been a means of transmission of acquired immune deficiency syndrome virus. Educational efforts have been directed at reduction of needle sharing, and some cities have supplied free needles. While transmission of human immunodeficiency virus through intravenous drug use remains significant problem, there…

  12. The Computer Aided Aircraft-design Package (CAAP)

    NASA Technical Reports Server (NTRS)

    Yalif, Guy U.

    1994-01-01

    The preliminary design of an aircraft is a complex, labor-intensive, and creative process. Since the 1970's, many computer programs have been written to help automate preliminary airplane design. Time and resource analyses have identified, 'a substantial decrease in project duration with the introduction of an automated design capability'. Proof-of-concept studies have been completed which establish 'a foundation for a computer-based airframe design capability', Unfortunately, today's design codes exist in many different languages on many, often expensive, hardware platforms. Through the use of a module-based system architecture, the Computer aided Aircraft-design Package (CAAP) will eventually bring together many of the most useful features of existing programs. Through the use of an expert system, it will add an additional feature that could be described as indispensable to entry level engineers and students: the incorporation of 'expert' knowledge into the automated design process.

  13. Designer Drug Confusion: A Focus on MDMA.

    ERIC Educational Resources Information Center

    Beck, Jerome; Morgan, Patricia A.

    1986-01-01

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

  14. Comments on the computer aided design of Stirling engines

    SciTech Connect

    Reader, G.T.; Taylor, D.R.

    1983-08-01

    For a number of years the research team at the Royal Naval Engineering College's Stirling Engine Research Facility (SERF) have been investigating the computer aided design of Stirling engines and these investigations have involved the study and review of existing analytical and computer techniques and the development of 'in-house' methods. In this paper these experiences are summarized against the background of the state-of-the-art in the field as represented by the existing literature. An attempt is made to delineate the various design and analytical methods available and to show that they all have their place in a fully integrated design package.

  15. Program Aids Design Of Fluid-Circulating Systems

    NASA Technical Reports Server (NTRS)

    Bacskay, Allen; Dalee, Robert

    1992-01-01

    Computer Aided Systems Engineering and Analysis (CASE/A) program is interactive software tool for trade study and analysis, designed to increase productivity during all phases of systems engineering. Graphics-based command-driven software package provides user-friendly computing environment in which engineer analyzes performance and interface characteristics of ECLS/ATC system. Useful during all phases of spacecraft-design program, from initial conceptual design trade studies to actual flight, including pre-flight prediction and in-flight analysis of anomalies. Written in FORTRAN 77.

  16. Computer-aided design of polymers and composites

    NASA Technical Reports Server (NTRS)

    Kaelble, D. H.

    1985-01-01

    This book on computer-aided design of polymers and composites introduces and discusses the subject from the viewpoint of atomic and molecular models. Thus, the origins of stiffness, strength, extensibility, and fracture toughness in composite materials can be analyzed directly in terms of chemical composition and molecular structure. Aspects of polymer composite reliability are considered along with characterization techniques for composite reliability, relations between atomic and molecular properties, computer aided design and manufacture, polymer CAD/CAM models, and composite CAD/CAM models. Attention is given to multiphase structural adhesives, fibrous composite reliability, metal joint reliability, polymer physical states and transitions, chemical quality assurance, processability testing, cure monitoring and management, nondestructive evaluation (NDE), surface NDE, elementary properties, ionic-covalent bonding, molecular analysis, acid-base interactions, the manufacturing science, and peel mechanics.

  17. Smarter Drugs: How Protein Crystallography Revolutionizes Drug Design

    SciTech Connect

    Smith, Clyde

    2005-04-26

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

  18. Computer-aided design of antenna structures and components

    NASA Technical Reports Server (NTRS)

    Levy, R.

    1976-01-01

    This paper discusses computer-aided design procedures for antenna reflector structures and related components. The primary design aid is a computer program that establishes cross sectional sizes of the structural members by an optimality criterion. Alternative types of deflection-dependent objectives can be selected for designs subject to constraints on structure weight. The computer program has a special-purpose formulation to design structures of the type frequently used for antenna construction. These structures, in common with many in other areas of application, are represented by analytical models that employ only the three translational degrees of freedom at each node. The special-purpose construction of the program, however, permits coding and data management simplifications that provide advantages in problem size and execution speed. Size and speed are essentially governed by the requirements of structural analysis and are relatively unaffected by the added requirements of design. Computation times to execute several design/analysis cycles are comparable to the times required by general-purpose programs for a single analysis cycle. Examples in the paper illustrate effective design improvement for structures with several thousand degrees of freedom and within reasonable computing times.

  19. Computer-aided conceptual design of Air Cushion Vehicles

    NASA Astrophysics Data System (ADS)

    Band, E. G. U.; Lavis, D. R.

    This paper describes the development and use of a computer-aided design tool which has been used to explore preferred options for amphibious Air-Cushion Vehicle (ACV) and Surface-Effect Ship (SES) designs in support of U.S. Navy and U.S. Army programs. The tool, referred to as the ACV Design Synthesis Model (ADSM), is an interactive computer program which provides a description of feasible ACV or SES concepts that could be developed, by a competent design team, to perform the mission described by the input parameters. The paper discusses how the program was used to explore parametrically the design of a range of self-propelled hoverbarges to meet requirements of the U.S. Army Logistics Over the Shore (LOTS) phases of an amphibious landing. Examples of results are presented to illustrate the method used in determining design and performance trade-offs.

  20. AIDS, HIV infection, and illicit drug use within inner-city families and social networks.

    PubMed Central

    Pivnick, A; Jacobson, A; Eric, K; Doll, L; Drucker, E

    1994-01-01

    OBJECTIVES. Drug use is commonly depicted and treated as an individual problem. This study describes the extent of drug use, human immunodeficiency virus (HIV) infection, and acquired immunodeficiency syndrome (AIDS) among drug users' sexual partners and family and household members in order to broaden considerations of risk. METHODS. Social network charts and structured interviews were administered to 126 women (predominantly African American and Latino) enrolled in methadone treatment. The charts elicited the prevalence of drug use and HIV infection among subjects' family and household members. RESULTS. Drug use and HIV/AIDS permeated subjects' sexual, familial, and household relationships. More than half of the women who resided with a sexual partner reported that their partners currently used drugs. Almost one third of the subjects' siblings were drug users. Of the 715 total siblings (all subjects plus their siblings), 69 (9.7%) were known to be HIV positive or to have an AIDS diagnosis. CONCLUSIONS. The sexual, familial, and household expressions of drug use underscore the notion that drug use and attendant risks, including but not limited to HIV infection, might be usefully viewed and treated as an inter- and intracommunity problem rather than as an exclusively individual one. PMID:8296952

  1. HIV/AIDS and Drug Abuse: Intertwined Epidemics

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... Medicine Abuse Electronic Cigarettes (e-Cigarettes) Fentanyl Hallucinogens Heroin Inhalants Is Marijuana Medicine? Marijuana MDMA (Ecstasy/Molly) ...

  2. Computer-Aided Design of a Sulfate Encapsulating Receptor

    SciTech Connect

    Custelcean, Radu; Bosano, Jerome J; Bonnesen, Peter V; Kertesz, Vilmos; Hay, Benjamin

    2009-01-01

    A promising new approach towards more efficient self-assembled cage receptors through computer-aided design is demonstrated. The resulting M{sub 4}L{sub 6} tetrahedral cage, internally functionalized with accurately positioned urea hydrogen-bonding groups (see structure; yellow: predicted, blue: experimental, space-filling: SO{sub 4}{sup 2-}), proved to be a remarkably strong sulfate receptor in water.

  3. Multistep Reaction Based De Novo Drug Design: Generating Synthetically Feasible Design Ideas.

    PubMed

    Masek, Brian B; Baker, David S; Dorfman, Roman J; DuBrucq, Karen; Francis, Victoria C; Nagy, Stephan; Richey, Bree L; Soltanshahi, Farhad

    2016-04-25

    We describe a "multistep reaction driven" evolutionary algorithm approach to de novo molecular design. Structures generated by the approach include a proposed synthesis path intended to aid the chemist in assessing the synthetic feasibility of the ideas that are generated. The methodology is independent of how the design ideas are scored, allowing multicriteria drug design to address multiple issues including activity at one or more pharmacological targets, selectivity, physical and ADME properties, and off target liabilities; the methods are compatible with common computer-aided drug discovery "scoring" methodologies such as 2D- and 3D-ligand similarity, docking, desirability functions based on physiochemical properties, and/or predictions from 2D/3D QSAR or machine learning models and combinations thereof to be used to guide design. We have performed experiments to assess the extent to which known drug space can be covered by our approach. Using a library of 88 generic reactions and a database of ∼20 000 reactants, we find that our methods can identify "close" analogs for ∼50% of the known small molecule drugs with molecular weight less than 300. To assess the quality of the in silico generated synthetic pathways, synthesis chemists were asked to rate the viability of synthesis pathways: both "real" and in silico generated. In silico reaction schemes generated by our methods were rated as very plausible with scores similar to known literature synthesis schemes. PMID:27031173

  4. The ethical design of an AIDS vaccine trial in Africa.

    PubMed

    Christakis, N A

    1988-01-01

    In 1987 in Zaire, a French investigator and a small group of Zairians were immunized with a French investigational AIDS vaccine. This action leads to questioning whether different sociocultural settings should have different research ethics applied, especially on pandemic diseases. Another question is to clarify the valid reasons for conducting an AIDS trial in Africa. The design of an AIDS vaccine trial should vary with the ethical and cultural factors of the research population involved, even if the epidemiological and scientific factors are the same worldwide. In Africa, study subjects meet the requirements for AIDS research: They are free from HIV infection and are at risk for the infection. However, concerns center on how to keep the subjects free from risks during the 6 months between HIV tests and how to ensure laboratory test accuracy. The applicability of the findings to that population are essential, although they may be unique to Africa. Research subjects must consent to participating in the trial and must be advised of their antibody status and of their becoming seropositive. To increase the beneficent treatment of subjects and decrease the risks, the study size should be increased and all participants should be counseled to avoid risky behaviors. A subject's family or social group may need to give consent in addition to the subject, because of cultural views. The explanation of the research must be in culturally relevant terms. Africa should have fair access to the vaccine resulting from the research. PMID:3397278

  5. Designer Drugs: A Synthetic Catastrophe

    PubMed Central

    Fratantonio, James; Andrade, Lawrence; Febo, Marcelo

    2016-01-01

    Synthetic stimulants can cause hallucinations, aggressive behaviors, death and are sometimes legal. These substances are sold as plant food and bath salts that are “Not for Human Consumption”, therefore skirting the 1986 Federal Analogue Act and giving a false pretense of safety. Studies have proved that these substances are toxic, have a high abuse potential, and are becoming extremely prevalent in the United States. This creates a dilemma for law enforcement agents, hospitals, and substance use disorder treatment centers. Urine Drug Testing is utilized as a clinical diagnostic tool in substance use disorder treatment centers, and the furious pace at which new synthetic stimulants are introduced to the black market are making the detection via urine increasingly difficult. This article will discuss the prevalence, pharmacology and difficulty developing laboratory assays to detect synthetic stimulants. PMID:27617301

  6. Evolution and intelligent design in drug development.

    PubMed

    Agafonov, Roman V; Wilson, Christopher; Kern, Dorothee

    2015-01-01

    Sophisticated protein kinase networks, empowering complexity in higher organisms, are also drivers of devastating diseases such as cancer. Accordingly, these enzymes have become major drug targets of the twenty-first century. However, the holy grail of designing specific kinase inhibitors aimed at specific cancers has not been found. Can new approaches in cancer drug design help win the battle with this multi-faced and quickly evolving enemy? In this perspective we discuss new strategies and ideas that were born out of a recent breakthrough in understanding the molecular basis underlying the clinical success of the cancer drug Gleevec. An "old" method, stopped-flow kinetics, combined with old enzymes, the ancestors dating back up to about billion years, provides an unexpected outlook for future intelligent design of drugs.

  7. Evolution and intelligent design in drug development

    PubMed Central

    Agafonov, Roman V.; Wilson, Christopher; Kern, Dorothee

    2015-01-01

    Sophisticated protein kinase networks, empowering complexity in higher organisms, are also drivers of devastating diseases such as cancer. Accordingly, these enzymes have become major drug targets of the twenty-first century. However, the holy grail of designing specific kinase inhibitors aimed at specific cancers has not been found. Can new approaches in cancer drug design help win the battle with this multi-faced and quickly evolving enemy? In this perspective we discuss new strategies and ideas that were born out of a recent breakthrough in understanding the molecular basis underlying the clinical success of the cancer drug Gleevec. An “old” method, stopped-flow kinetics, combined with old enzymes, the ancestors dating back up to about billion years, provides an unexpected outlook for future intelligent design of drugs. PMID:26052517

  8. HIV/AIDS and Drug Use in China—Interactions, Impacts, and Issues

    PubMed Central

    Zhao, Min; Ling, Walter

    2014-01-01

    The interrelationships of HIV/AIDS and drug use and misuse result in complex problems that have been addressed by a variety of sociolegal approaches that often are in contrast to evidence-based medical practices proven effective in reducing associated harms. Like other countries struggling to reduce the incidence and consequences of addiction and HIV/AIDS, China is working to improve systems of care and to revise policies toward drug use and misuse and HIV/AIDS. Greater interaction with researchers and clinicians from around the world can foster increased awareness of effective practices and help implement effective strategies to deal with the problems of HIV/AIDS, and addiction. PMID:22676569

  9. Role of community pharmacies in prevention of AIDS among injecting drug misusers: findings of a survey in England and Wales.

    PubMed Central

    Glanz, A.; Byrne, C.; Jackson, P.

    1989-01-01

    OBJECTIVE--To determine the current and potential roles of community pharmacists in the prevention of AIDS among misusers of injected drugs. DESIGN--Cross sectional postal survey of a one in four random sample of registered pharmacies in England and Wales. SETTING--Project conducted in the addiction research unit of the Institute of Psychiatry, London. SUBJECTS--2469 Community pharmacies in the 15 regional health authorities in England and Wales. MAIN OUTCOME MEASURES--Willingness of pharmacists to sell injecting equipment to known or suspected misusers of drugs; pharmacists' attitudes to syringe exchange schemes, keeping a "sharps" box for use by misusers of drugs, and offering face to face advice and leaflets; and opinions of community pharmacists on their role in AIDS prevention and drug misuse. RESULTS--1946 Questionnaires were returned, representing a response rate of 79%. This fell short of the target of one in four pharmacies in each family practitioner committee area in England and Wales, and total numbers of respondents were therefore weighted in inverse proportion to the response rate in each area. The findings disclosed a substantial demand for injecting equipment by drug misusers. After weighting of numbers of respondents an estimated 676 of 2434 pharmacies were currently selling injecting equipment and 65 of 2415 (3%) were participating in local syringe exchange schemes; only 94 of 2410 pharmacies (4%) had a sharps box for used equipment. There was a high degree of concern among pharmacists about particular consequences of drug misusers visiting their premises, along with a widespread acceptance that the community pharmacist had an important part to play. CONCLUSIONS--Promoting the participation of community pharmacists in the prevention of AIDS among misusers of injected drugs is a viable policy, but several problems would need to be overcome before it was implemented. PMID:2511969

  10. The Design Manager's Aid for Intelligent Decomposition (DeMAID)

    NASA Technical Reports Server (NTRS)

    Rogers, James L.

    1994-01-01

    Before the design of new complex systems such as large space platforms can begin, the possible interactions among subsystems and their parts must be determined. Once this is completed, the proposed system can be decomposed to identify its hierarchical structure. The design manager's aid for intelligent decomposition (DeMAID) is a knowledge based system for ordering the sequence of modules and identifying a possible multilevel structure for design. Although DeMAID requires an investment of time to generate and refine the list of modules for input, it could save considerable money and time in the total design process, particularly in new design problems where the ordering of the modules has not been defined.

  11. Computer-aided structural design of a lunar radio telescope

    NASA Technical Reports Server (NTRS)

    Akgul, Ferhat; Gerstle, Walter H.; Johnson, Stewart W.

    1990-01-01

    This paper describes a computer-aided structural design of the main reflector of a fully steerable radio telescope to be located (in the 21st century) on the moon, and presents the results of the structural analysis of the reflector. The reflector is a paraboloid with a surface area of 12,660 sq m and a focal ratio of 0.42. The reflector's surface will be covered by a 5.08 cm-thick sandwich panel made of thin-walled aluminum cells filled with low-density foam. The low weight of the design will be achieved by using graphite-epoxy as the structural material.

  12. Three-Dimensional Computer Aided Design of a Vertical Winnower

    NASA Astrophysics Data System (ADS)

    Bao, Yumei; Lin, Saijia; Weng, Lijie

    The research states home and abroad of the winnowing technology and winnowers are reviewed in brief. For the air duct, the core component of the winnower, the relevant technical parameters in the winnowing process are calculated based on the winnowing principle. The three-dimensional computer aided design (3D-CAD) software Solidworks is applied. The designed vertical winnower is able to separate different raw materials by adjusting the air speed and has been put into practical production to separate the Chinese traditional medicine with high separating effect.

  13. New Animal Model Could Boost Research on AIDS Drugs and Vaccines | Poster

    Cancer.gov

    By Frank Blanchard, Staff Writer, and Jeff Lifson, Guest Writer In a research milestone reported in the June 20 issue of the journal Science, scientists have developed a minimally modified version of HIV-1, the virus that causes AIDS in infected humans, that is capable of causing progressive infection and AIDS in monkeys. The advance should help create more authentic animal models of the disease and provide a potentially invaluable approach for faster and better preclinical evaluation of new drugs and vaccines.

  14. Multidisciplinary Expert-aided Analysis and Design (MEAD)

    NASA Technical Reports Server (NTRS)

    Hummel, Thomas C.; Taylor, James

    1989-01-01

    The MEAD Computer Program (MCP) is being developed under the Multidisciplinary Expert-Aided Analysis and Design (MEAD) Project as a CAD environment in which integrated flight, propulsion, and structural control systems can be designed and analyzed. The MCP has several embedded computer-aided control engineering (CACE) packages, a user interface (UI), a supervisor, a data-base manager (DBM), and an expert system (ES). The supervisor monitors and coordinates the operation of the CACE packages, the DBM; the ES, and the UI. The DBM tracks the control design process. Models created or installed by the MCP are tracked by date and version, and results are associated with the specific model version with which they were generated. The ES is used to relieve the control engineer from tedious and cumbersome tasks in the iterative design process. The UI provides the capability for a novice as well as an expert to utilize the MCP easily and effectively. The MCP version 2(MCP-2.0) is fully developed for flight control system design and analysis. Propulsion system modeling, analysis, and simulation is also supported; the same is true for structural models represented in state-space form. The ultimate goal is to cover the integration of flight, propulsion, and structural control engineering, including all discipline-specific functionality and interfaces. The current MCP-2.0 components and functionality are discussed.

  15. Computational Methods Applied to Rational Drug Design

    PubMed Central

    Ramírez, David

    2016-01-01

    Due to the synergic relationship between medical chemistry, bioinformatics and molecular simulation, the development of new accurate computational tools for small molecules drug design has been rising over the last years. The main result is the increased number of publications where computational techniques such as molecular docking, de novo design as well as virtual screening have been used to estimate the binding mode, site and energy of novel small molecules. In this work I review some tools, which enable the study of biological systems at the atomistic level, providing relevant information and thereby, enhancing the process of rational drug design. PMID:27708723

  16. The analysis of HIV/AIDS drug-resistant on networks

    NASA Astrophysics Data System (ADS)

    Liu, Maoxing

    2014-01-01

    In this paper, we present an Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) drug-resistant model using an ordinary differential equation (ODE) model on scale-free networks. We derive the threshold for the epidemic to be zero in infinite scale-free network. We also prove the stability of disease-free equilibrium (DFE) and persistence of HIV/AIDS infection. The effects of two immunization schemes, including proportional scheme and targeted vaccination, are studied and compared. We find that targeted strategy compare favorably to a proportional condom using has prominent effect to control HIV/AIDS spread on scale-free networks.

  17. Visions of visualization aids - Design philosophy and observations

    NASA Technical Reports Server (NTRS)

    Ellis, Stephen R.

    1989-01-01

    Aids for the visualization of high-dimensional scientific or other data must be designed. Simply casting multidimensional data into a two-dimensional or three-dimensional spatial metaphor does not guarantee that the presentation will provide insight or a parsimonious description of phenomena implicit in the data. Useful visualization, in contrast to glitzy, high-tech, computer-graphics imagery, is generally based on preexisting theoretical beliefs concerning the underlying phenomena. These beliefs guide selection and formatting of the plotted variables. Visualization tools are useful for understanding naturally three-dimensional data bases such as those used by pilots or astronauts. Two examples of such aids for spatial maneuvering illustrate that informative geometric distortion may be introduced to assist visualization and that visualization of complex dynamics alone may not be adequate to provide the necessary insight into the underlying processes.

  18. Viral sequence diversity: challenges for AIDS vaccine designs

    PubMed Central

    McBurney, Sean P; Ross, Ted M

    2009-01-01

    Among the greatest challenges facing AIDS vaccine development is the intrinsic diversity among circulating populations of HIV-1 in various geographical locations and the need to develop vaccines that can elicit enduring protective immunity to variant HIV-1 strains. While variation is observed in all of the viral proteins, the greatest diversity is localized to the viral envelope glycoproteins, evidently reflecting the predominant role of these proteins in eliciting host immune recognition and responses that result in progressive evolution of the envelope proteins during persistent infection. Interestingly, while envelope glycoprotein variation is widely assumed to be a major obstacle to AIDS vaccine development, there is very little experimental data in animal or human lentivirus systems addressing this critical issue. In this review, the state of vaccine development to address envelope diversity will be presented, focusing on the use of centralized and polyvalent sequence design as mechanisms to elicit broadly reactive immune responses. PMID:18980542

  19. Evolution of Geometric Sensitivity Derivatives from Computer Aided Design Models

    NASA Technical Reports Server (NTRS)

    Jones, William T.; Lazzara, David; Haimes, Robert

    2010-01-01

    The generation of design parameter sensitivity derivatives is required for gradient-based optimization. Such sensitivity derivatives are elusive at best when working with geometry defined within the solid modeling context of Computer-Aided Design (CAD) systems. Solid modeling CAD systems are often proprietary and always complex, thereby necessitating ad hoc procedures to infer parameter sensitivity. A new perspective is presented that makes direct use of the hierarchical associativity of CAD features to trace their evolution and thereby track design parameter sensitivity. In contrast to ad hoc methods, this method provides a more concise procedure following the model design intent and determining the sensitivity of CAD geometry directly to its respective defining parameters.

  20. The ergonomics of computer aided design within advanced manufacturing technology.

    PubMed

    John, P A

    1988-03-01

    Many manufacturing companies have now awakened to the significance of computer aided design (CAD), although the majority of them have only been able to purchase computerised draughting systems of which only a subset produce direct manufacturing data. Such companies are moving steadily towards the concept of computer integrated manufacture (CIM), and this demands CAD to address more than draughting. CAD architects are thus having to rethink the basic specification of such systems, although they typically suffer from an insufficient understanding of the design task and have consequently been working with inadequate specifications. It is at this fundamental level that ergonomics has much to offer, making its contribution by encouraging user-centred design. The discussion considers the relationships between CAD and: the design task; the organisation and people; creativity; and artificial intelligence. It finishes with a summary of the contribution of ergonomics.

  1. Designing Drug Trials: Considerations for Pregnant Women

    PubMed Central

    Sheffield, Jeanne S.; Siegel, David; Mirochnick, Mark; Heine, R. Phillips; Nguyen, Christine; Bergman, Kimberly L.; Savic, Rada M.; Long, Jill; Dooley, Kelly E.; Nesin, Mirjana

    2014-01-01

    Clinical pharmacology studies that describe the pharmacokinetics and pharmacodynamics of drugs in pregnant women are critical for informing on the safe and effective use of drugs during pregnancy. That being said, multiple factors have hindered the ability to study drugs in pregnant patients. These include concerns for maternal and fetal safety, ethical considerations, the difficulty in designing appropriate trials to assess the study objectives, and funding limitations. This document summarizes the recommendations of a panel of experts convened by the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. These experts were charged with reviewing the issues related to the development of preclinical and clinical drug studies in pregnant women and to develop strategies for addressing these issues. These findings may also be utilized in the development of future drug studies involving pregnant women and their fetus/neonate. PMID:25425722

  2. Nanogel Carrier Design for Targeted Drug Delivery

    PubMed Central

    Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

    2014-01-01

    Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

  3. Targeted proteins for diabetes drug design

    NASA Astrophysics Data System (ADS)

    Doan Trang Nguyen, Ngoc; Thi Le, Ly

    2012-03-01

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

  4. Magnetic nanotherapeutics for dysregulated synaptic plasticity during neuroAIDS and drug abuse.

    PubMed

    Sagar, Vidya; Atluri, Venkata Subba Rao; Pilakka-Kanthikeel, Sudheesh; Nair, Madhavan

    2016-01-01

    The human immunodeficiency virus (HIV) is a neurotropic virus. It induces neurotoxicity and subsequent brain pathologies in different brain cells. Addiction to recreational drugs remarkably affects the initiation of HIV infections and expedites the progression of acquired immunodeficiency syndrome (AIDS) associated neuropathogenesis. Symptoms of HIV-associated neurocognitive disorders (HAND) are noticed in many AIDS patients. At least 50 % of HIV diagnosed cases show one or other kind of neuropathological signs or symptoms during different stages of disease progression. In the same line, mild to severe neurological alterations are seen in at least 80 % autopsies of AIDS patients. Neurological illnesses weaken the connections between neurons causing significant altercations in synaptic plasticity. Synaptic plasticity alterations during HIV infection and recreational drug abuse are mediated by complex cellular phenomena involving changes in gene expression and subsequent loss of dendritic and spine morphology and physiology. New treatment strategies with ability to deliver drugs across blood-brain barrier (BBB) are being intensively investigated. In this context, magnetic nanoparticles (MNPs) based nanoformulations have shown significant potential for target specificity, drug delivery, drug release, and bioavailability of desired amount of drugs in non-invasive brain targeting. MNPs-based potential therapies to promote neuronal plasticity during HIV infection and recreational drug abuse are being developed. PMID:27216740

  5. Microwave processing of a dental ceramic used in computer-aided design/computer-aided manufacturing.

    PubMed

    Pendola, Martin; Saha, Subrata

    2015-01-01

    Because of their favorable mechanical properties and natural esthetics, ceramics are widely used in restorative dentistry. The conventional ceramic sintering process required for their use is usually slow, however, and the equipment has an elevated energy consumption. Sintering processes that use microwaves have several advantages compared to regular sintering: shorter processing times, lower energy consumption, and the capacity for volumetric heating. The objective of this study was to test the mechanical properties of a dental ceramic used in computer-aided design/computer-aided manufacturing (CAD/CAM) after the specimens were processed with microwave hybrid sintering. Density, hardness, and bending strength were measured. When ceramic specimens were sintered with microwaves, the processing times were reduced and protocols were simplified. Hardness was improved almost 20% compared to regular sintering, and flexural strength measurements suggested that specimens were approximately 50% stronger than specimens sintered in a conventional system. Microwave hybrid sintering may preserve or improve the mechanical properties of dental ceramics designed for CAD/CAM processing systems, reducing processing and waiting times.

  6. Single-tooth dento-osseous osteotomy with a computer-aided design/computer-aided manufacturing surgical guide

    PubMed Central

    2016-01-01

    This clinical note introduces a method to assist surgeons in performing single-tooth dento-osseous osteotomy. For use in this method, a surgical guide was manufactured using computer-aided design/computer-aided manufacturing technology and was based on preoperative surgical simulation data. This method was highly conducive to successful single-tooth dento-osseous segmental osteotomy. PMID:27162756

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

    ERIC Educational Resources Information Center

    Havas, George D.

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

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

    PubMed Central

    Oprea, Tudor I.; Nielsen, Sonny Kim; Ursu, Oleg; Yang, Jeremy J.; Taboureau, Olivier; Mathias, Stephen L.; Kouskoumvekaki, lrene; Sklar, Larry A.; Bologa, Cristian G.

    2012-01-01

    Finding new uses for old drugs is a strategy embraced by the pharmaceutical industry, with increasing participation from the academic sector. Drug repurposing efforts focus on identifying novel modes of action, but not in a systematic manner. With intensive data mining and curation, we aim to apply bio- and cheminformatics tools using the DRUGS database, containing 3,837 unique small molecules annotated on 1,750 proteins. These are likely to serve as drug targets and antitargets (i.e., associated with side effects, SE). The academic community, the pharmaceutical sector and clinicians alike could benefit from an integrated, semantic-web compliant computer-aided drug repurposing (CADR) effort, one that would enable deep data mining of associations between approved drugs (D), targets (T), clinical outcomes (CO) and SE. We report preliminary results from text mining and multivariate statistics, based on 7,684 approved drug labels, ADL (Dailymed) via text mining. From the ADL corresponding to 988 unique drugs, the “adverse reactions” section was mapped onto 174 SE, then clustered via principal component analysis into a 5x5 self-organizing map that was integrated into a Cytoscape network of SE-D-T-CO. This type of data can be used to streamline drug repurposing and may result in novel insights that can lead to the identification of novel drug actions. PMID:22287994

  9. 21 CFR 516.24 - Granting MUMS-drug designation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Granting MUMS-drug designation. 516.24 Section 516.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation...

  10. 21 CFR 516.24 - Granting MUMS-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Granting MUMS-drug designation. 516.24 Section 516.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation...

  11. 21 CFR 516.24 - Granting MUMS-drug designation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Granting MUMS-drug designation. 516.24 Section 516.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation...

  12. 21 CFR 516.24 - Granting MUMS-drug designation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Granting MUMS-drug designation. 516.24 Section 516.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation...

  13. Non-polymeric nano-carriers in HIV/AIDS drug delivery and targeting.

    PubMed

    Gupta, Umesh; Jain, Narendra K

    2010-03-18

    Development of an effective drug delivery approach for the treatment of HIV/AIDS is a global challenge. The conventional drug delivery approaches including Highly Active Anti Retroviral Therapy (HAART) have increased the life span of the HIV/AIDS patient. However, the eradication of HIV is still not possible with these approaches due to some limitations. Emergence of polymeric and non-polymeric nanotechnological approaches can be opportunistic in this direction. Polymeric carriers like, dendrimers and nanoparticles have been reported for the targeting of anti HIV drugs. The synthetic pathways as well polymeric framework create some hurdles in their successful formulation development as well as in the possible drug delivery approaches. In the present article, we have discussed the general physiological aspects of the infection along with the relevance of non-polymeric nanocarriers like liposomes, solid lipid nanoparticles (SLN), ethosomes, etc. in the treatment of this disastrous disease. PMID:19913579

  14. Designer drugs 2015: assessment and management.

    PubMed

    Weaver, Michael F; Hopper, John A; Gunderson, Erik W

    2015-03-25

    Recent designer drugs, also known as "legal highs," include substituted cathinones (e.g., mephedrone, methylone, and methylenedioxypyrovalerone, often referred to as "bath salts"); synthetic cannabinoids (SCs; e.g., Spice); and synthetic hallucinogens (25I-NBOMe, or N-bomb). Compound availability has evolved rapidly to evade legal regulation and detection by routine drug testing. Young adults are the primary users, but trends are changing rapidly; use has become popular among members of the military. Acute toxicity is common and often manifests with a constellation of psychiatric and medical effects, which may be severe (e.g., anxiety, agitation, psychosis, and tachycardia), and multiple deaths have been reported with each of these types of designer drugs. Clinicians should keep designer drugs in mind when evaluating substance use in young adults or in anyone presenting with acute neuropsychiatric complaints. Treatment of acute intoxication involves supportive care targeting manifesting signs and symptoms. Long-term treatment of designer drug use disorder can be challenging and is complicated by a lack of evidence to guide treatment.

  15. Defining Patient Centric Pharmaceutical Drug Product Design.

    PubMed

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

    2016-09-01

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

  16. A Conceptual Design of a Departure Planner Decision Aid

    NASA Technical Reports Server (NTRS)

    Anagnostakis, Ioannis; Idris, Husni R.; Clark, John-Paul; Feron, Eric; Hansman, R. John; Odoni, Amedeo R.; Hall, William D.

    2000-01-01

    Terminal area Air Traffic Management handles both arriving and departing traffic. To date, research work on terminal area operations has focused primarily on the arrival flow and typically departures are taken into account only in an approximate manner. However, arrivals and departures are highly coupled processes especially in the terminal airspace, with complex interactions and sharing of the same airport resources between arrivals and departures taking place in practically every important terminal area. Therefore, the addition of automation aids for departures, possibly in co-operation with existing arrival flow automation systems, could have a profound contribution in enhancing the overall efficiency of airport operations. This paper presents the conceptual system architecture for such an automation aid, the Departure Planner (DP). This architecture can be used as a core in the development of decision-aiding systems to assist air traffic controllers in improving the performance of departure operations and optimize runway time allocation among different operations at major congested airports. The design of such systems is expected to increase the overall efficiency of terminal area operations and yield benefits for all stakeholders involved in Air Traffic Management (ATM) operations, users as well as service providers.

  17. Visions of visualization aids: Design philosophy and experimental results

    NASA Technical Reports Server (NTRS)

    Ellis, Stephen R.

    1990-01-01

    Aids for the visualization of high-dimensional scientific or other data must be designed. Simply casting multidimensional data into a two- or three-dimensional spatial metaphor does not guarantee that the presentation will provide insight or parsimonious description of the phenomena underlying the data. Indeed, the communication of the essential meaning of some multidimensional data may be obscured by presentation in a spatially distributed format. Useful visualization is generally based on pre-existing theoretical beliefs concerning the underlying phenomena which guide selection and formatting of the plotted variables. Two examples from chaotic dynamics are used to illustrate how a visulaization may be an aid to insight. Two examples of displays to aid spatial maneuvering are described. The first, a perspective format for a commercial air traffic display, illustrates how geometric distortion may be introduced to insure that an operator can understand a depicted three-dimensional situation. The second, a display for planning small spacecraft maneuvers, illustrates how the complex counterintuitive character of orbital maneuvering may be made more tractable by removing higher-order nonlinear control dynamics, and allowing independent satisfaction of velocity and plume impingement constraints on orbital changes.

  18. [Russia: sex, drugs, AIDS and the Doctors Without Borders].

    PubMed

    Veeken, H

    1998-05-16

    Russia faces a serious crisis and finds it difficult to look after all its citizens. Alcoholics, homeless and elderly fight to survive. A recent problem is the rapid increase in the number of injecting drug users. In Moscow an estimated 100,000 users form an important core group for HIV transmission. With the health system collapsed and sexually transmitted diseases on the rise, all ingredients for a HIV epidemic are present. By the turn of the century the Ministry of Health forecasts 800,000 HIV positives. Médecins sans Frontières in co-operation with the government started a HIV prevention campaign. PMID:9623240

  19. CATIA - A computer aided design and manufacturing tridimensional system

    NASA Astrophysics Data System (ADS)

    Bernard, F.

    A properietary computer graphics-aided, three-dimensional interactive application (CATIA) design system is described. CATIA employs approximately 100 graphics displays, which are used by some 500 persons engaged in the definition of aircraft structures, structural strength analyses, the kinematic analysis of mobile elements, aerodynamic calculations, the choice of tooling in the machining of aircraft elements, and the programming of robotics. CATIA covers these diverse fields with a single data base. After a description of salient aspects of the system's hardware and software, graphics examples are given of the definition of curves, surfaces, complex volumes, and analytical tasks.

  20. Computer-aided design of bevel gear tooth surfaces

    NASA Technical Reports Server (NTRS)

    Shuo, Hung Chang; Huston, Ronald L.; Coy, John J.

    1989-01-01

    This paper presents a computer-aided design procedure for generating bevel gears. The development is based on examining a perfectly plastic, cone-shaped gear blank rolling over a cutting tooth on a plane crown rack. The resulting impression on the plastic gear blank is the envelope of the cutting tooth. This impression and envelope thus form a conjugate tooth surface. Equations are presented for the locus of points on the tooth surface. The same procedures are then extended to simulate the generation of a spiral bevel gear. The corresponding governing equations are presented.

  1. Computer aided design of bevel gear tooth surfaces

    NASA Technical Reports Server (NTRS)

    Chang, S. H.; Huston, R. L.; Coy, J. J.

    1989-01-01

    This paper presents a computer-aided design procedure for generating bevel gears. The development is based on examining a perfectly plastic, cone-shaped gear blank rolling over a cutting tooth on a plane crown rack. The resulting impression on the plastic gear blank is the envelope of the cutting tooth. This impression and envelope thus form a conjugate tooth surface. Equations are presented for the locus of points on the tooth surface. The same procedures are then extended to simulate the generation of a spiral bevel gear. The corresponding governing equations are presented.

  2. Computer aided design and analysis of gear tooth geometry

    NASA Technical Reports Server (NTRS)

    Chang, S. H.; Huston, R. L.

    1987-01-01

    A simulation method for gear hobbing and shaping of straight and spiral bevel gears is presented. The method is based upon an enveloping theory for gear tooth profile generation. The procedure is applicable in the computer aided design of standard and nonstandard tooth forms. An inverse procedure for finding a conjugate gear tooth profile is presented for arbitrary cutter geometry. The kinematic relations for the tooth surfaces of straight and spiral bevel gears are proposed. The tooth surface equations for these gears are formulated in a manner suitable for their automated numerical development and solution.

  3. Accelerating Battery Design Using Computer-Aided Engineering Tools: Preprint

    SciTech Connect

    Pesaran, A.; Heon, G. H.; Smith, K.

    2011-01-01

    Computer-aided engineering (CAE) is a proven pathway, especially in the automotive industry, to improve performance by resolving the relevant physics in complex systems, shortening the product development design cycle, thus reducing cost, and providing an efficient way to evaluate parameters for robust designs. Academic models include the relevant physics details, but neglect engineering complexities. Industry models include the relevant macroscopic geometry and system conditions, but simplify the fundamental physics too much. Most of the CAE battery tools for in-house use are custom model codes and require expert users. There is a need to make these battery modeling and design tools more accessible to end users such as battery developers, pack integrators, and vehicle makers. Developing integrated and physics-based CAE battery tools can reduce the design, build, test, break, re-design, re-build, and re-test cycle and help lower costs. NREL has been involved in developing various models to predict the thermal and electrochemical performance of large-format cells and has used in commercial three-dimensional finite-element analysis and computational fluid dynamics to study battery pack thermal issues. These NREL cell and pack design tools can be integrated to help support the automotive industry and to accelerate battery design.

  4. Conformational transition paths harbor structures useful for aiding drug discovery and understanding enzymatic mechanisms in protein kinases.

    PubMed

    Wong, Chung F

    2016-01-01

    This short article examines the usefulness of fast simulations of conformational transition paths in elucidating enzymatic mechanisms and guiding drug discovery for protein kinases. It applies the transition path method in the MOIL software package to simulate the paths of conformational transitions between six pairs of structures from the Protein Data Bank. The structures along the transition paths were found to resemble experimental structures that mimic transient structures believed to form during enzymatic catalysis or conformational transitions, or structures that have drug candidates bound. These findings suggest that such simulations could provide quick initial insights into the enzymatic mechanisms or pathways of conformational transitions of proteins kinases, or could provide structures useful for aiding structure-based drug design.

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

    PubMed Central

    Shelate, Pragna; Dave, Divyang

    2016-01-01

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

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

    PubMed Central

    Shelate, Pragna; Dave, Divyang

    2016-01-01

    The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

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

    PubMed

    Patel, Apurv; Dodiya, Hitesh; Shelate, Pragna; Shastri, Divyesh; Dave, Divyang

    2016-01-01

    The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

  8. Beliefs about AIDS, Use of Alcohol and Drugs, and Unprotected Sex among Massachusetts Adolescents.

    ERIC Educational Resources Information Center

    Hingson, Ralph W.; And Others

    1990-01-01

    Surveyed 1,773 Massachusetts adolescents to explore relationships among the following topics: (1) alcohol and drug use; (2) perceived susceptibility to human immunodeficiency virus (HIV); (3) use of condoms; (4) effectiveness of condoms in preventing infection; (5) barriers to condom use; and (6) behavioral cues about AIDS related to condom use.…

  9. New rules for new drugs: the challenge of AIDS to the regulatory process.

    PubMed

    Edgar, Harold; Rothman, David J

    1990-01-01

    AIDS is systematically changing attitudes and practices regarding the regulation and use of drugs. The complex framework and rigorous research protocols developed by the Food and Drug Administration prior to the 1980s to minimize risk to subjects is shifting in the epidemic's wake to maximize innovation. The FDA has adopted new procedures hastening access to investigational drugs and easing drug importation for personal use, which, in effect, transfers decisions about the benefits and risks of drugs from the agency's staff to patients and their physicians. While the FDA's tilt toward embracing consumer rights may continue in the near future, disappointing results could prompt the agency to reassert its authority in controlling drug policy more restrictively.

  10. Advances in computer-aided design and computer-aided manufacture technology.

    PubMed

    Calamia, J R

    1996-01-01

    Although the development of computer-aided design (CAD) and computer-aided manufacture (CAM) technology and the benefits of increased productivity became obvious in the automobile and aerospace industries in the 1970s, investigations of this technology's application in the field of dentistry did not begin until the 1980s. Only now are we beginning to see the fruits of this work with the commercial availability of some systems; the potential for this technology seems boundless. This article reviews the recent literature with emphasis on the period from June 1992 to May 1993. This review should familiarize the reader with some of the latest developments in this technology, including a brief description of some systems currently available and the clinical and economical rationale for their acceptance into the dental mainstream. This article concentrates on a particular system, the Cerec (Siemens/Pelton and Crane, Charlotte, NC) system, for three reasons: First, this system has been available since 1985 and, as a result, has a track record of almost 7 years of data. Most of the data have just recently been released and consequently, much of this year's literature on CAD-CAM is monopolized by studies using this system. Second, this system was developed as a mobile, affordable, direct chairside CAD-CAM restorative method. As such, it is of special interest to the patient, providing a one-visit restoration. Third, the author is currently engaged in research using this particular system and has a working knowledge of this system's capabilities.

  11. A spreadsheet for AIDS: estimating heterosexual injection drug user population size from AIDS statistics in San Francisco.

    PubMed

    Aldrich, M R; Mandel, J; Newmeyer, J A

    1990-01-01

    A single-page computer spreadsheet can be used to back-calculate the size of the population at risk from the reported number of AIDS cases and HIV seropositivity levels for that population. However, Cohen (1988:35) has cautioned that "this method requires some heroic assumptions, and is, therefore, fraught with difficulty." Slight variations in the definition of AIDS, in the progression rate, and in reported seropositivity rates used as data in the spreadsheet can make enormous differences in the results obtained through back-calculation. Despite the limitations of the method, an estimate of the possible size of the IDU population can be derived from back-calculation, with careful consideration of ethnographic realities taken into account. In San Francisco, the present authors believe that there were approximately 13,000 heterosexual IDUs as of the end of 1989. Further demographic divisions by ethnicity, age, sex, and even neighborhood could be made using the same techniques, if AIDS cases and seropositivity levels could be obtained for each variable. Table II predicts a cumulative 705 AIDS diagnoses among San Francisco heterosexual IDUs by the end of 1993, or nearly six times as many as reported through 1988. This prediction is based on an assumption of 2.5% seroconversion per year (1989-1993) and on modest progression-rate increments of 5%, 5%, 4%, 3%, and 3% in the eleventh through fifteenth years after HIV infection. Thus, it shows the magnitude of the epidemic that San Francisco will shortly face and emphasizes the need to act vigorously to prevent further HIV contagion among IDUs as well as from them to their heterosexual partners (drug using or not).(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Nanostructured Delivery Systems: Augmenting the Delivery of Antiretroviral Drugs for Better Management of HIV/AIDS.

    PubMed

    Singh, Gurinder; Pai, Roopa S; Mustafa, Sanaul

    2015-01-01

    In the last two decades, HIV-1, the retrovirus associated with acquired immunodeficiency syndrome (AIDS), is globally one of the primary causes of morbidity and mortality. Unfortunately, existing approaches for interventions are not able to suppress the progression of infection due to this virus. Of the many obstacles, viral entry into the mono-nuclear phagocyte system encompassing monocytes/macrophages and dendritic cells is a major concern. Viral infection is also responsible for the subsequent distribution of the virus into various tissues throughout the organism. Tremendous progress has been made during the past few years to diagnose and treat patients with HIV/AIDS infection, yet much remains to be done. Recommended treatment involves long-term and multiple drug therapy that causes severe side effects. With almost 12% of the world population suffering from HIV/AIDS, better management of this global threat is highly desired. Nanostructured delivery systems hold promise for improving the situation. Such systems can facilitate the uptake of antiretroviral drugs, causing a considerable improvement in HIV/AIDS therapy. Nanoscale systems have intriguing potential to drastically improve existing HIV/AIDS diagnosis and treatment platforms. Nanosystems constitute a wide range of systems varying from polymeric nanoparticles, to solid-lipid nanoparticles, liposomes, micro- and nanoemulsions, dendrimers, and self-nanoemulsifying systems. Improved bioavailability, solubility, stability, and biocompatibility make them an ideal choice for delivery of antiretroviral drugs. The present review initially describes an updated bird's-eye view account of the literature. Then, we provide a relatively sententious overview on updated patents of recent nanostructured delivery systems for antiretroviral drugs. Finally, we discuss low-cost therapy (such as antioxidants and immune modulators) for the treatment and prevention of HIV/AIDS. PMID:26559551

  13. Knowledge of AIDS and HIV transmission among drug users in Rio de Janeiro, Brazil

    PubMed Central

    2011-01-01

    Background Proper knowledge of HIV transmission is not enough for people to adopt protective behaviors, but deficits in this information may increase HIV/AIDS vulnerability. Objective To assess drug users' knowledge of HIV/AIDS and the possible association between knowledge and HIV testing. Methods A Cross-sectional study conducted in 2006/7 with a convenience sample of 295 illicit drug users in Rio de Janeiro, assessing knowledge on AIDS/HIV transmission and its relationship with HIV testing. Information from 108 randomly selected drug users who received an educational intervention using cards illustrating situations potentially associated with HIV transmission were assessed using Multidimensional Scaling (MDS). Results Almost 40% of drug users reported having never used condoms and more than 60% reported not using condoms under the influence of substances. Most drug users (80.6%) correctly answered that condoms make sex safer, but incorrect beliefs are still common (e.g. nearly 44% believed HIV can be transmitted through saliva and 55% reported that HIV infection can be transmitted by sharing toothbrushes), with significant differences between drug users who had and who had not been tested for HIV. MDS showed queries on vaginal/anal sex and sharing syringes/needles were classified in the same set as effective modes of HIV transmission. The event that was further away from this core of properly perceived risks referred to blood donation, perceived as risky. Other items were found to be dispersed, suggesting inchoate beliefs on transmission modes. Conclusions Drug users have an increased HIV infection vulnerability compared to the general population, this specific population expressed relevant doubts about HIV transmission, as well as high levels of risky behavior. Moreover, the findings suggest that possessing inaccurate HIV/AIDS knowledge may be a barrier to timely HIV testing. Interventions should be tailored to such specific characteristics. PMID:21324119

  14. A review of computer-aided design/computer-aided manufacture techniques for removable denture fabrication.

    PubMed

    Bilgin, Mehmet Selim; Baytaroğlu, Ebru Nur; Erdem, Ali; Dilber, Erhan

    2016-01-01

    The aim of this review was to investigate usage of computer-aided design/computer-aided manufacture (CAD/CAM) such as milling and rapid prototyping (RP) technologies for removable denture fabrication. An electronic search was conducted in the PubMed/MEDLINE, ScienceDirect, Google Scholar, and Web of Science databases. Databases were searched from 1987 to 2014. The search was performed using a variety of keywords including CAD/CAM, complete/partial dentures, RP, rapid manufacturing, digitally designed, milled, computerized, and machined. The identified developments (in chronological order), techniques, advantages, and disadvantages of CAD/CAM and RP for removable denture fabrication are summarized. Using a variety of keywords and aiming to find the topic, 78 publications were initially searched. For the main topic, the abstract of these 78 articles were scanned, and 52 publications were selected for reading in detail. Full-text of these articles was gained and searched in detail. Totally, 40 articles that discussed the techniques, advantages, and disadvantages of CAD/CAM and RP for removable denture fabrication and the articles were incorporated in this review. Totally, 16 of the papers summarized in the table. Following review of all relevant publications, it can be concluded that current innovations and technological developments of CAD/CAM and RP allow the digitally planning and manufacturing of removable dentures from start to finish. As a result according to the literature review CAD/CAM techniques and supportive maxillomandibular relationship transfer devices are growing fast. In the close future, fabricating removable dentures will become medical informatics instead of needing a technical staff and procedures. However the methods have several limitations for now.

  15. A review of computer-aided design/computer-aided manufacture techniques for removable denture fabrication.

    PubMed

    Bilgin, Mehmet Selim; Baytaroğlu, Ebru Nur; Erdem, Ali; Dilber, Erhan

    2016-01-01

    The aim of this review was to investigate usage of computer-aided design/computer-aided manufacture (CAD/CAM) such as milling and rapid prototyping (RP) technologies for removable denture fabrication. An electronic search was conducted in the PubMed/MEDLINE, ScienceDirect, Google Scholar, and Web of Science databases. Databases were searched from 1987 to 2014. The search was performed using a variety of keywords including CAD/CAM, complete/partial dentures, RP, rapid manufacturing, digitally designed, milled, computerized, and machined. The identified developments (in chronological order), techniques, advantages, and disadvantages of CAD/CAM and RP for removable denture fabrication are summarized. Using a variety of keywords and aiming to find the topic, 78 publications were initially searched. For the main topic, the abstract of these 78 articles were scanned, and 52 publications were selected for reading in detail. Full-text of these articles was gained and searched in detail. Totally, 40 articles that discussed the techniques, advantages, and disadvantages of CAD/CAM and RP for removable denture fabrication and the articles were incorporated in this review. Totally, 16 of the papers summarized in the table. Following review of all relevant publications, it can be concluded that current innovations and technological developments of CAD/CAM and RP allow the digitally planning and manufacturing of removable dentures from start to finish. As a result according to the literature review CAD/CAM techniques and supportive maxillomandibular relationship transfer devices are growing fast. In the close future, fabricating removable dentures will become medical informatics instead of needing a technical staff and procedures. However the methods have several limitations for now. PMID:27095912

  16. A review of computer-aided design/computer-aided manufacture techniques for removable denture fabrication

    PubMed Central

    Bilgin, Mehmet Selim; Baytaroğlu, Ebru Nur; Erdem, Ali; Dilber, Erhan

    2016-01-01

    The aim of this review was to investigate usage of computer-aided design/computer-aided manufacture (CAD/CAM) such as milling and rapid prototyping (RP) technologies for removable denture fabrication. An electronic search was conducted in the PubMed/MEDLINE, ScienceDirect, Google Scholar, and Web of Science databases. Databases were searched from 1987 to 2014. The search was performed using a variety of keywords including CAD/CAM, complete/partial dentures, RP, rapid manufacturing, digitally designed, milled, computerized, and machined. The identified developments (in chronological order), techniques, advantages, and disadvantages of CAD/CAM and RP for removable denture fabrication are summarized. Using a variety of keywords and aiming to find the topic, 78 publications were initially searched. For the main topic, the abstract of these 78 articles were scanned, and 52 publications were selected for reading in detail. Full-text of these articles was gained and searched in detail. Totally, 40 articles that discussed the techniques, advantages, and disadvantages of CAD/CAM and RP for removable denture fabrication and the articles were incorporated in this review. Totally, 16 of the papers summarized in the table. Following review of all relevant publications, it can be concluded that current innovations and technological developments of CAD/CAM and RP allow the digitally planning and manufacturing of removable dentures from start to finish. As a result according to the literature review CAD/CAM techniques and supportive maxillomandibular relationship transfer devices are growing fast. In the close future, fabricating removable dentures will become medical informatics instead of needing a technical staff and procedures. However the methods have several limitations for now. PMID:27095912

  17. Computer-aided auditing of prescription drug claims.

    PubMed

    Iyengar, Vijay S; Hermiz, Keith B; Natarajan, Ramesh

    2014-09-01

    We describe a methodology for identifying and ranking candidate audit targets from a database of prescription drug claims. The relevant audit targets may include various entities such as prescribers, patients and pharmacies, who exhibit certain statistical behavior indicative of potential fraud and abuse over the prescription claims during a specified period of interest. Our overall approach is consistent with related work in statistical methods for detection of fraud and abuse, but has a relative emphasis on three specific aspects: first, based on the assessment of domain experts, certain focus areas are selected and data elements pertinent to the audit analysis in each focus area are identified; second, specialized statistical models are developed to characterize the normalized baseline behavior in each focus area; and third, statistical hypothesis testing is used to identify entities that diverge significantly from their expected behavior according to the relevant baseline model. The application of this overall methodology to a prescription claims database from a large health plan is considered in detail.

  18. "Drugs and AIDS--reaching for help": a videotape on AIDS and drug abuse prevention for criminal justice populations.

    PubMed

    Gross, M; DeJong, W; Lamb, D; Enos, T; Mason, T; Weitzman, E

    1994-01-01

    This article describes the development of a videotape targeted at persons under supervision of the criminal justice system. The videotape seeks to encourage those who use illicit drugs to enter drug treatment and to motivate those at risk for exposure to human immunodeficiency virus (HIV) to alter behaviors that may transmit infection. The criminal justice system presents an important opportunity to deliver such messages, particularly to a large population of persons briefly detained in a jail or lockup and released without subsequent incarceration. Evidence suggests that, even in this audience, knowledge of how to prevent exposure to HIV is widespread, yet those at risk often fail to take appropriate precautions: motivating behavior change demands more than imparting information. In order to shape this videotape, we analyzed the target audience and developed a drama-based approach that applies the framework of social learning theory, the health belief model, and principles of social marketing. This article describes the integration of that theoretical framework into the production process, content, and strategy of the videotape.

  19. 'Flu' and structure-based drug design.

    PubMed

    Wade, R C

    1997-09-15

    The threat of a catastrophic outbreak of influenza is ever present. Vaccines are only partially effective and the two compounds, amantidine and rimantidine, used clinically against influenza A cause side-effects and rapid viral resistance. Recent advances bring hope that specific and potent drugs against influenza may soon be available in the clinic. These compounds were designed to inhibit influenza neuraminidase (NA), one of the viral coat glycoproteins, using the crystal structure of NA which was first published in 1983. In this review, the application of structure-based drug design approaches to the design of anti-influenza agents targeted at NA and haemagglutinin (HA), the other viral surface glycoprotein, is discussed. PMID:9331424

  20. Computer aided design environment for the analysis and design of multi-body flexible structures

    NASA Technical Reports Server (NTRS)

    Ramakrishnan, Jayant V.; Singh, Ramen P.

    1989-01-01

    A computer aided design environment consisting of the programs NASTRAN, TREETOPS and MATLAB is presented in this paper. With links for data transfer between these programs, the integrated design of multi-body flexible structures is significantly enhanced. The CAD environment is used to model the Space Shuttle/Pinhole Occulater Facility. Then a controller is designed and evaluated in the nonlinear time history sense. Recent enhancements and ongoing research to add more capabilities are also described.

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

    PubMed Central

    Santos, Lucianna Helene; Ferreira, Rafaela Salgado; Caffarena, Ernesto Raúl

    2015-01-01

    Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted. PMID:26560977

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

    PubMed

    Santos, Lucianna Helene; Ferreira, Rafaela Salgado; Caffarena, Ernesto Raúl

    2015-11-01

    Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted. PMID:26560977

  3. Toward the computer-aided design of metal ion sequestering agents

    SciTech Connect

    Hay, Benjamin P.; Firman, Timothy K.; Lumetta, Gregg J.; Rapko, Brian M.; Garza, Priscilla A.; Sinkov, Sergei I.; Hutchison, James E.; Parks, Bevin W.; Gilbertson, Robert D.; Weakley, Timothy J R

    2004-07-14

    The concepts embodied in de novo structure-based drug design are being adapted for the computer-aided design of metal ion sequestering agents. This adaptation requires the development of methods for (i) generating candidate structures and (ii) evaluating and prioritizing these structures with respect to their binding affinity for a specific guest. This article summarizes recent progress in this area that includes the creation of a new computer software program, called HostDesigner, that can generate and evaluate millions of new molecular structures per minute on a desktop personal computer. Several methods for evaluating the degree of binding site organization in a host structure are presented. An example is provided to demonstrate how these methods have been used to identify ligand architectures that provide enhanced metal ion binding affinity.

  4. The application of computer-aided technologies in automotive styling design

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

  5. Counting on natural products for drug design

    NASA Astrophysics Data System (ADS)

    Rodrigues, Tiago; Reker, Daniel; Schneider, Petra; Schneider, Gisbert

    2016-06-01

    Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.

  6. Similarity in drugs: reflections on analogue design.

    PubMed

    Wermuth, Camille G

    2006-04-01

    A survey of novel small-molecule therapeutics reveals that the majority of them result from analogue design and that their market value represents two-thirds of all small-molecule sales. In natural science, the term analogue, derived from the Latin and Greek analogia, has always been used to describe structural and functional similarity. Extended to drugs, this definition implies that the analogue of an existing drug molecule shares structural and pharmacological similarities with the original compound. Formally, this definition allows the establishment of three categories of drug analogues: analogues possessing chemical and pharmacological similarities (direct analogues); analogues possessing structural similarities only (structural analogues); and chemically different compounds displaying similar pharmacological properties (functional analogues). PMID:16580977

  7. A digital patient for computer-aided prosthesis design

    PubMed Central

    Colombo, Giorgio; Facoetti, Giancarlo; Rizzi, Caterina

    2013-01-01

    This article concerns the design of lower limb prosthesis, both below and above knee. It describes a new computer-based design framework and a digital model of the patient around which the prosthesis is designed and tested in a completely virtual environment. The virtual model of the patient is the backbone of the whole system, and it is based on a biomechanical general-purpose model customized with the patient's characteristics (e.g. anthropometric measures). The software platform adopts computer-aided and knowledge-guided approaches with the goal of replacing the current development process, mainly hand made, with a virtual one. It provides the prosthetics with a set of tools to design, configure and test the prosthesis and comprehends two main environments: the prosthesis modelling laboratory and the virtual testing laboratory. The first permits the three-dimensional model of the prosthesis to be configured and generated, while the second allows the prosthetics to virtually set up the artificial leg and simulate the patient's postures and movements, validating its functionality and configuration. General architecture and modelling/simulation tools for the platform are described as well as main aspects and results of the experimentation. PMID:24427528

  8. Advances in computer-aided design and computer-aided manufacture technology.

    PubMed

    Calamia, J R

    1994-01-01

    Although the development of computer-aided design (CAD) and computer-aided manufacture (CAM) technology and the benefits of increased productivity became obvious in the automobile and aerospace industries in the 1970s, investigations of this technology's application in the field of dentistry did not begin until the 1980s. Only now are we beginning to see the fruits of this work with the commercial availability of some systems; the potential for this technology seems boundless. This article reviews the recent literature with emphasis on the period from June 1992 to May 1993. This review should familiarize the reader with some of the latest developments in this technology, including a brief description of some systems currently available and the clinical and economical rationale for their acceptance into the dental mainstream. This article concentrates on a particular system, the Cerec (Siemens/Pelton and Crane, Charlotte, NC) system, for three reasons: first, this system has been available since 1985 and, as a result, has a track record of almost 7 years of data. Most of the data have just recently been released and consequently, much of this year's literature on CAD-CAM is monopolized by studies using this system. Second, this system was developed as a mobile, affordable, direct chairside CAD-CAM restorative method. As such, it is of special interest to the dentist who will offer this new technology directly to the patient, providing a one-visit restoration. Third, the author is currently engaged in research using this particular system and has a working knowledge of this system's capabilities.

  9. Design of HIV Protease Inhibitors Targeting Protein Backbone: An Effective Strategy for Combating Drug Resistance

    SciTech Connect

    Ghosh, Arun K.; Chapsal, Bruno D.; Weber, Irene T.; Mitsuya, Hiroaki

    2008-06-03

    The discovery of human immunodeficiency virus (HIV) protease inhibitors (PIs) and their utilization in highly active antiretroviral therapy (HAART) have been a major turning point in the management of HIV/acquired immune-deficiency syndrome (AIDS). However, despite the successes in disease management and the decrease of HIV/AIDS-related mortality, several drawbacks continue to hamper first-generation protease inhibitor therapies. The rapid emergence of drug resistance has become the most urgent concern because it renders current treatments ineffective and therefore compels the scientific community to continue efforts in the design of inhibitors that can efficiently combat drug resistance.

  10. HIV/AIDS prevention among female sexual partners of injection drug users in Ciudad Juarez, Mexico.

    PubMed

    Ferreira-Pinto, J B; Ramos, R

    1995-01-01

    A participatory community project in the US-Mexico border town of Ciudad Juarez, aimed at helping women who are sex partners of male injection drug users to reduce behaviours which increase their risk for HIV infection, is described and evaluated. The design and implementation of the project were influenced by Paulo Freire's pedagogy in the Latin American tradition of 'popular' education, by Bandura's self-efficacy concepts, and by David Warner's 'barefoot doctor' community health care methodology. Using these approaches the participants were directly involved in the development of teaching materials, and curriculum content and implementation of the project. The programme was evaluated quantitatively using NIDA's AIDS Intake and Follow-up Assessment (AIA/AFA) questionnaires, and qualitatively using open ended interviews. While the AIA/AFA questionnaires detected small changes in the frequency of condom use among the participants, ethnographic interviews detected significant changes in the nature of the behaviours which were placing the women at risk. The changes seem to stem from an increase in the degree of self-esteem, self-efficacy and awareness of the social, economic, and political constraints of their lives. These results demonstrate the need for qualitative measures to be incorporated in the evaluation of community based health education programmes. A series of recommendations is presented to facilitate further development and replication of the programme in similar populations.

  11. Evaluation of some compression aids in tableting of roller compacted swellable core drug layer.

    PubMed

    Golchert, D; Bines, E; Carmody, A

    2013-09-10

    Swellable core technology (SCT) represents a broadly applicable oral osmotic drug delivery platform for the controlled release of drugs. SCT tablets control drug delivery by using osmosis to regulate the influx of water into the tablet's core. The tablet consists of two layers; drug layer and sweller layer, with a semi-permeable membrane coating and delivery port located in the drug layer side of the tablet. The key component of SCT formulations is polyethylene oxide (PEO), which is typically wet granulated with organic solvents to prevent rapid gel hydration observed during contact with aqueous environments. However, the use of organic solvents has their own environmental and cost considerations which make this form of processing undesirable. To overcome this issue, dry granulation can be employed. However, PEO is a very plastic material and problems may be encountered during the tableting process, when work hardening occurs upon double compression. The addition of compression aids to the drug layer will help to increase the roll force when generating ribbons - reducing fines and segregation potential - while also reducing work hardening effects which impact tablet friability. The five compression aids used in this study were microcrystalline cellulose (MCC), xylitol, di-calcium phosphate (anhydrous), lactose monohydrate and starch. The work undertaken here studies the compression properties of the drug layer blends with different levels of the five compression aids as part of the formulation. Roller compaction properties are also varied to provide granules with differing solid fractions. The results of this study indicate that addition of microcrystalline cellulose in the formulation in levels between 10% and 30% significantly improve the tablet hardness at lower tablet compression forces. Further work is required to investigate the impact on dissolution. PMID:23796839

  12. AIDS education for drug abusers: evaluation of short-term effectiveness.

    PubMed Central

    McCusker, J; Stoddard, A M; Zapka, J G; Morrison, C S; Zorn, M; Lewis, B F

    1992-01-01

    BACKGROUND. Interventions are needed to assist drug abusers in reducing risky drug and sexual behavior. METHODS. A randomized controlled trial compared three small-group AIDS educational interventions among 567 clients of a 21-day inpatient drug detoxification program: a two-session informational intervention, given either during the first (early) or second (late) week of treatment; and a six-session enhanced intervention. Changes in knowledge, attitudes, and psychomotor skills were assessed before and after each intervention, and behavioral outcomes were assessed at follow-up 10 to 18 weeks after admission. RESULTS. Immediately after the interventions, enhanced group members reported significantly greater self-efficacy to talk themselves out of AIDS-risky behavior; other knowledge and attitude scales did not differ by intervention. At follow-up, significant reductions in risky drug use were reported by all groups. Enhanced group members reported significantly greater reduction in injection frequency than did late informational subjects. CONCLUSIONS. No beneficial effect was detected of delaying AIDS education for clients entering detoxification. At this early stage of follow-up, there is only weak evidence that an enhanced intervention improved outcomes. PMID:1546770

  13. Computer aided microbial safety design of food processes.

    PubMed

    Schellekens, M; Martens, T; Roberts, T A; Mackey, B M; Nicolaï, B M; Van Impe, J F; De Baerdemaeker, J

    1994-12-01

    To reduce the time required for product development, to avoid expensive experimental tests, and to quantify safety risks for fresh products and the consequence of processing there is a growing interest in computer aided food process design. This paper discusses the application of hybrid object-oriented and rule-based expert system technology to represent the data and knowledge of microbial experts and food engineers. Finite element models for heat transfer calculation routines, microbial growth and inactivation models and texture kinetics are combined with food composition data, thermophysical properties, process steps and expert knowledge on type and quantity of microbial contamination. A prototype system has been developed to evaluate changes in food composition, process steps and process parameters on microbiological safety and textual quality of foods.

  14. From paper drawings to computer-aided design

    NASA Astrophysics Data System (ADS)

    Karima, M.; Sadhal, K. S.; McNeil, T. O.

    1985-02-01

    The benefits of a fully integrated computer-aided design and drafting system (CADDS) database are today very well accepted by industry, and major engineering companies implementing CADDS are confronted with the gigantic task of entering the existing multidisciplinary engineering information into the CADDS database. The present investigation is concerned with the findings of a feasibility study which had been conducted by a Canadian company to explore data capture on engineering drawings. A review of the state of the art in digitization is presented, and attention is given to specific problems arising in the case of the Canadian company. It is found that substantial advancements have been made toward the automatic 'reading' of existing drawings on paper media. However, no system exists currently which fully automates the data capturing process in the engineering environment and generates intelligent databases for use by CADD systems. Suitable approaches for 'data capture' under the given conditions are discussed.

  15. Visual display aid for orbital maneuvering - Design considerations

    NASA Technical Reports Server (NTRS)

    Grunwald, Arthur J.; Ellis, Stephen R.

    1993-01-01

    This paper describes the development of an interactive proximity operations planning system that allows on-site planning of fuel-efficient multiburn maneuvers in a potential multispacecraft environment. Although this display system most directly assists planning by providing visual feedback to aid visualization of the trajectories and constraints, its most significant features include: (1) the use of an 'inverse dynamics' algorithm that removes control nonlinearities facing the operator, and (2) a trajectory planning technique that separates, through a 'geometric spreadsheet', the normally coupled complex problems of planning orbital maneuvers and allows solution by an iterative sequence of simple independent actions. The visual feedback of trajectory shapes and operational constraints, provided by user-transparent and continuously active background computations, allows the operator to make fast, iterative design changes that rapidly converge to fuel-efficient solutions. The planning tool provides an example of operator-assisted optimization of nonlinear cost functions.

  16. Using a Latino Lens to Reimagine Aid Design and Delivery

    ERIC Educational Resources Information Center

    Santiago, Deborah A.

    2013-01-01

    Federal financial aid is critical to student access and success in postsecondary education for many students, including most Latinos. However, three current realities are challenging the effectiveness of federal financial aid policy today: (1) the inability of federal aid to keep pace with the increase in college costs for students; (2) the…

  17. Accessible haptic technology for drug design applications.

    PubMed

    Zonta, Nicola; Grimstead, Ian J; Avis, Nick J; Brancale, Andrea

    2009-02-01

    Structure-based drug design is a creative process that displays several features that make it closer to human reasoning than to machine automation. However, very often the user intervention is limited to the preparation of the input and analysis of the output of a computer simulation. In some cases, allowing human intervention directly in the process could improve the quality of the results by applying the researcher intuition directly into the simulation. Haptic technology has been previously explored as a useful method to interact with a chemical system. However, the need of expensive hardware and the lack of accessible software have limited the use of this technology to date. Here we are reporting the implementation of a haptic-based molecular mechanics environment aimed for interactive drug design and ligand optimization, using an easily accessible software/hardware combination. PMID:19048316

  18. Drug design from the cryptic inhibitor envelope

    PubMed Central

    Lee, Chul-Jin; Liang, Xiaofei; Wu, Qinglin; Najeeb, Javaria; Zhao, Jinshi; Gopalaswamy, Ramesh; Titecat, Marie; Sebbane, Florent; Lemaitre, Nadine; Toone, Eric J.; Zhou, Pei

    2016-01-01

    Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors of LpxC—an essential enzyme of the lipid A biosynthetic pathway in Gram-negative bacteria and a validated novel antibiotic target—access alternative, minor population states in solution in addition to the ligand conformation observed in crystal structures. These conformations collectively delineate an inhibitor envelope that is invisible to crystallography, but is dynamically accessible by small molecules in solution. Drug design exploiting such a hidden inhibitor envelope has led to the development of potent antibiotics with inhibition constants in the single-digit picomolar range. The principle of the cryptic inhibitor envelope approach may be broadly applicable to other lead optimization campaigns to yield improved therapeutics. PMID:26912110

  19. Hardware synthesis from DDL. [Digital Design Language for computer aided design and test of LSI

    NASA Technical Reports Server (NTRS)

    Shah, A. M.; Shiva, S. G.

    1981-01-01

    The details of the digital systems can be conveniently input into the design automation system by means of Hardware Description Languages (HDL). The Computer Aided Design and Test (CADAT) system at NASA MSFC is used for the LSI design. The Digital Design Language (DDL) has been selected as HDL for the CADAT System. DDL translator output can be used for the hardware implementation of the digital design. This paper addresses problems of selecting the standard cells from the CADAT standard cell library to realize the logic implied by the DDL description of the system.

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

    NASA Technical Reports Server (NTRS)

    Kolb, Mark A.

    1990-01-01

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

  1. The AIDS epidemic among Spanish drug users: a birth cohort-associated phenomenon.

    PubMed Central

    Castilla, J; Pollán, M; López-Abente, G

    1997-01-01

    OBJECTIVES: In Spain the number of new acquired immunodeficiency syndrome (AIDS) cases among injection drug users continues to rise. The time trend up to 1994 has been analyzed, with special attention paid to the different generations. METHODS: The source for injection drug use-related cases was the Spanish AIDS Register. Independent analyses of annual specific rates were run for each sex with the use of an age-period-cohort log-linear model. RESULTS: After adjustment for age and year of diagnosis, AIDS incidence related to injection drug use is associated with specific birth cohorts. Rising values are observed in the successive generations born during the 1950s, peaking in men born in 1962 and women born in 1964. In subsequent cohorts, there is a marked falloff in incidence for both sexes, but this decline is seen to halt in men from the 1972 birth cohort onwards. The overall period effect is upward, yet the trend flattens in the last years. There is a pronounced age effect with maximum values in men and women at ages 29 and 27, respectively. CONCLUSIONS: It is essential to urge avoidance of risk behaviors in new generations. PMID:9184504

  2. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment

    PubMed Central

    Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A.; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A.; Nekhai, Sergei; Akala, Emmanuel O.

    2016-01-01

    Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

  3. Adherence to HIV/AIDS antiretroviral therapy among drug users: A qualitative study in Iran

    PubMed Central

    Hosseini, Zahra; Eftkhar, Hasan; Nedjat, Saharnaz; Ebadi, Abbas; Abbasian, Ladan; Zamani, Fereshte; Aghamollaei, Teamur; Shojaeizade, Davood

    2016-01-01

    Background: The introduction of antiretroviral therapy has caused a remarkable decrease in the occurrence of diseases and mortality among HIV-positive patients, while this success has not been achieved among injection addicts due to a low adherence to antiretroviral medicine. This study aims at clarifying the important factors affecting adherence to treatment in addicts suffering from HIV. Materials and Methods: In this qualitative research, data were gathered through in-depth interviews and field notes, and were interpreted through content analysis in the form of constant comparison. The participants were 16 drug addicts living with HIV/AIDS. Most of them had records of imprisonment and were receiving Highly Active Antiretroviral Therapy (HAART) drug treatments in the AIDS center of Imam Khomeini Hospital complex, affiliated to Tehran University of Medical Sciences. Sampling was started in a purposive method and was continued until data were saturated. Results: Four main categories including psychological reactions, contradictory beliefs, perceived support, and individual and environmental barriers were extracted from the data, each having some sub-categories. Conclusions: The obtained results indicated that adherence to the treatment of HIV is not constant and mono-dimensional, but is a function of different factors. Hence, an individual having feeble adherence in a specific time and under specific circumstances may show desirable adherence under a different circumstance. Thus, treatment of addicts living with HIV/AIDS requires physical, psychological, and social attention along with drug treatments. PMID:26985220

  4. TOWARD THE COMPUTER-AIDED DESIGN OF ION SEQUESTERING AGENTS

    SciTech Connect

    Hay, Benjamin

    2008-01-01

    A major impediment to introduction of new extractants to practical use is the large cost and long lead times for synthesis and testing of candidate molecules. Toward the goal of reducing this experimental burden, this talk describes a computational approach to the design of molecular receptors that are structurally organized for optimal coordination with ions. With a molecular-level understanding of how host architecture influences ion-binding affinity, it is possible to identify promising potential extractants before they are prepared and tested. Exploiting powerful concepts embodied in structure-based drug design to bear on host design, we have devised novel algorithms for building potential host structures from molecular fragments and rapid methods for comparing the binding-site organization of the resulting candidates. The result is a computer software program, called HostDesigner, which can generate and evaluate millions of new molecular structures per minute on a desktop personal computer. The utility of this software has been illustrated in the structural design of cation receptors such as crown ethers and anion receptors bearing urea groups.

  5. Injection drug use and HIV/AIDS in China: review of current situation, prevention and policy implications.

    PubMed

    Qian, Han-Zhu; Schumacher, Joseph E; Chen, Huey T; Ruan, Yu-Hua

    2006-01-01

    Illicit drug abuse and HIV/AIDS have increased rapidly in the past 10 to 20 years in China. This paper reviews drug abuse in China, the HIV/AIDS epidemic and its association with injection drug use (IDU), and Chinese policies on illicit drug abuse and prevention of HIV/AIDS based on published literature and unpublished official data. As a major drug trans-shipment country with source drugs from the "Golden Triangle" and "Gold Crescent" areas in Asia, China has also become an increasingly important drug consuming market. About half of China's 1.14 million documented drug users inject, and many share needles. IDU has contributed to 42% of cumulatively reported HIV/AIDS cases thus far. Drug trafficking is illegal in China and can lead to the death penalty. The public security departments adopt "zero tolerance" approach to drug use, which conflict with harm reduction policies of the public health departments. Past experience in China suggests that cracking down on drug smuggling and prohibiting drug use alone can not prevent or solve all illicit drug related problems in the era of globalization. In recent years, the central government has outlined a series of pragmatic policies to encourage harm reduction programs; meanwhile, some local governments have not fully mobilized to deal with drug abuse and HIV/AIDS problems seriously. Strengthening government leadership at both central and local levels; scaling up methadone substitution and needle exchange programs; making HIV voluntary counseling and testing available and affordable to both urban and rural drug users; and increasing utilization of outreach and nongovernmental organizations are offered as additional strategies to help cope with China's HIV and drug abuse problem.

  6. A situational picture of HIV/AIDS and injection drug use in Vinnitsya, Ukraine

    PubMed Central

    Barcal, Katerina; Schumacher, Joseph E; Dumchev, Kostyantyn; Moroz, Larisa Vasiliyevna

    2005-01-01

    Background New and explosive HIV epidemics are being witnessed in certain countries of Eastern Europe, including Ukraine, as well as a rapid and dramatic increase in the supply, use, and negative public health consequences of illicit drugs. A majority of registered HIV cases in Ukraine occur among injection drug users (IDUs), large numbers of whom report HIV risk behaviors such as needle sharing. The purpose of this study was to apply the World Health Organization's Rapid Assessment and Response on Injection Drug Use (IDU-RAR) guide to create a situational picture in the Vinnitsya Oblast, Ukraine, a region with very scarce information about the HIV/AIDS and injection drug use (IDU) epidemics. Methods The IDU-RAR uses a combination of qualitative data collection techniques commonly employed in social science and evaluation research to quickly depict the extent and nature of the given health problem and propose locally relevant recommendations for improvement. The investigators focused their assessment on the contextual factors, drug use, and intervention and policy components of the IDU-RAR. A combination of network and block sampling techniques was used. Data collection methods included direct observation, review of existing data, structured and unstructured interviews, and focus group discussions. Key informants and locations were visited until no new information was being generated. Results The number of registered HIV cases in Vinnitsya has increased from 3 (1987–1995) to 860 (1999–10/2004), 57 of whom have already died. Ten percent of annual admissions to the area's Regional Narcological Dispensary were for opiate disorders, and the number of registered IDUs rose by 20% from 1999 to 2000. The level of HIV/AIDS awareness is generally poor among the general population but high among high-risk populations. Both HIV/AIDS and injection drug use carry a strong stigma in the community, even among medical professionals. There was very little evidence of primary HIV/AIDS

  7. A critically appraised topic review of computer-aided design/computer-aided machining of removable partial denture frameworks.

    PubMed

    Lang, Lisa A; Tulunoglu, Ibrahim

    2014-01-01

    A critically appraised topic (CAT) review is presented about the use of computer-aided design (CAD)/computer-aided machining (CAM) removable partial denture (RPD) frameworks. A systematic search of the literature supporting CAD/CAM RPD systems revealed no randomized clinical trials, hence the CAT review was performed. A PubMed search yielded 9 articles meeting the inclusion criteria. Each article was characterized by study design and level of evidence. No clinical outcomes research has been published on the use of CAD/CAM RPDs. Low levels of evidence were found in the available literature. Clinical research studies are needed to determine the efficacy of this treatment modality.

  8. [Designer drugs--diagnostic, psychological and low aspects of problem].

    PubMed

    Morawska-Siudak, Jowanka; Szkolnicka, Beata; Gomółka, Ewa; Krawczyk-Pasławska, Elzbieta

    2010-01-01

    Designer drugs used often by teenagers have simulative, relaxing, hallucinogenic and psychedelic properties. The biological action, addictive potential, diagnostic problems and low regulations related to designer drugs are presented in the study.

  9. Structures of HIV Protease Guide Inhibitor Design to Overcome Drug Resistance

    SciTech Connect

    Weber, Irene T.; Kovalevsky, Andrey Y.; Harrison, Robert W.

    2008-06-03

    The HIV/AIDS infection continues to be a major epidemic worldwide despite the initial promise of antiviral drugs. Current therapy includes a combination of drugs that inhibit two of the virally-encoded enzymes, the reverse transcriptase and the protease. The first generation of HIV protease inhibitors that have been in clinical use for treatment of AIDS since 1995 was developed with the aid of structural analysis of protease-inhibitor complexes. These drugs were successful in improving the life span of HIV-infected people. Subsequently, the rapid emergence of drug resistance has necessitated the design of new inhibitors that target mutant proteases. This second generation of antiviral protease inhibitors has been developed with the aid of data from medicinal chemistry, kinetics, and X-ray crystallographic analysis. Traditional computational methods such as molecular mechanics and dynamics can be supplemented with intelligent data mining approaches. One approach, based on similarities to the protease interactions with substrates, is to incorporate additional interactions with main chain atoms that cannot easily be eliminated by mutations. Our structural and inhibition data for darunavir have helped to understand its antiviral activity and effectiveness on drug resistant HIV and demonstrate the success of this approach.

  10. Perceptions of the Design of Voice Output Communication Aids

    ERIC Educational Resources Information Center

    Judge, Simon; Townend, Gillian

    2013-01-01

    Background: Voice output communication aids (VOCAs) are a key form of aided communication within the field of augmentative and alternative communication (AAC). In recent years, rapid developments in technology have resulted in an explosion of devices available commercially, yet little research has been conducted into what people who use VOCAs…

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

    PubMed

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

    2016-01-01

    Despite the tremendous improvement in overall global health heralded by the adoption of the Millennium Declaration in the year 2000, tropical infections remain a major health problem in the developing world. Recent estimates indicate that the major tropical infectious diseases, namely, malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for more than 2.2 million deaths and a loss of approximately 85 million disability-adjusted life years annually. The crucial role of chemotherapy in curtailing the deleterious health and economic impacts of these infections has invigorated the search for new drugs against tropical infectious diseases. The research efforts have involved increased application of computational technologies in mainstream drug discovery programs at the hit identification, hit-to-lead, and lead optimization stages. This review highlights various computer-aided drug discovery approaches that have been utilized in efforts to identify novel antimalarial, antitubercular, antitrypanosomal, and antileishmanial agents. The focus is largely on developments over the past 5 years (2010-2014). PMID:27622945

  12. DEMAID - A DESIGN MANAGER'S AID FOR INTELLIGENT DECOMPOSITION (SUN VERSION)

    NASA Technical Reports Server (NTRS)

    Rogers, J. L.

    1994-01-01

    Many engineering systems are large and multi-disciplinary. Before the design of new complex systems such as large space platforms can begin, the possible interactions among subsystems and their parts must be determined. Once this is completed the proposed system can be decomposed to identify its hierarchical structure. DeMAID (A Design Manager's Aid for Intelligent Decomposition) is a knowledge-based system for ordering the sequence of modules and identifying a possible multilevel structure for the design problem. DeMAID displays the modules in an N x N matrix format (called a design structure matrix) where a module is any process that requires input and generates an output. (Modules which generate an output but do not require an input, such as an initialization process, are also acceptable.) Although DeMAID requires an investment of time to generate and refine the list of modules for input, it could save a considerable amount of money and time in the total design process, particularly in new design problems where the ordering of the modules has not been defined. The decomposition of a complex design system into subsystems requires the judgement of the design manager. DeMAID reorders and groups the modules based on the links (interactions) among the modules, helping the design manager make decomposition decisions early in the design cycle. The modules are grouped into circuits (the subsystems) and displayed in an N x N matrix format. Feedback links, which indicate an iterative process, are minimized and only occur within a subsystem. Since there are no feedback links among the circuits, the circuits can be displayed in a multilevel format. Thus, a large amount of information is reduced to one or two displays which are stored for later retrieval and modification. The design manager and leaders of the design teams then have a visual display of the design problem and the intricate interactions among the different modules. The design manager could save a substantial

  13. DEMAID - A DESIGN MANAGER'S AID FOR INTELLIGENT DECOMPOSITION (MACINTOSH VERSION)

    NASA Technical Reports Server (NTRS)

    Rogers, J. L.

    1994-01-01

    Many engineering systems are large and multi-disciplinary. Before the design of new complex systems such as large space platforms can begin, the possible interactions among subsystems and their parts must be determined. Once this is completed the proposed system can be decomposed to identify its hierarchical structure. DeMAID (A Design Manager's Aid for Intelligent Decomposition) is a knowledge-based system for ordering the sequence of modules and identifying a possible multilevel structure for the design problem. DeMAID displays the modules in an N x N matrix format (called a design structure matrix) where a module is any process that requires input and generates an output. (Modules which generate an output but do not require an input, such as an initialization process, are also acceptable.) Although DeMAID requires an investment of time to generate and refine the list of modules for input, it could save a considerable amount of money and time in the total design process, particularly in new design problems where the ordering of the modules has not been defined. The decomposition of a complex design system into subsystems requires the judgement of the design manager. DeMAID reorders and groups the modules based on the links (interactions) among the modules, helping the design manager make decomposition decisions early in the design cycle. The modules are grouped into circuits (the subsystems) and displayed in an N x N matrix format. Feedback links, which indicate an iterative process, are minimized and only occur within a subsystem. Since there are no feedback links among the circuits, the circuits can be displayed in a multilevel format. Thus, a large amount of information is reduced to one or two displays which are stored for later retrieval and modification. The design manager and leaders of the design teams then have a visual display of the design problem and the intricate interactions among the different modules. The design manager could save a substantial

  14. DEMAID - A DESIGN MANAGER'S AID FOR INTELLIGENT DECOMPOSITION (SUN VERSION)

    NASA Technical Reports Server (NTRS)

    Rogers, J. L.

    1994-01-01

    Many engineering systems are large and multi-disciplinary. Before the design of new complex systems such as large space platforms can begin, the possible interactions among subsystems and their parts must be determined. Once this is completed the proposed system can be decomposed to identify its hierarchical structure. DeMAID (A Design Manager's Aid for Intelligent Decomposition) is a knowledge-based system for ordering the sequence of modules and identifying a possible multilevel structure for the design problem. DeMAID displays the modules in an N x N matrix format (called a design structure matrix) where a module is any process that requires input and generates an output. (Modules which generate an output but do not require an input, such as an initialization process, are also acceptable.) Although DeMAID requires an investment of time to generate and refine the list of modules for input, it could save a considerable amount of money and time in the total design process, particularly in new design problems where the ordering of the modules has not been defined. The decomposition of a complex design system into subsystems requires the judgement of the design manager. DeMAID reorders and groups the modules based on the links (interactions) among the modules, helping the design manager make decomposition decisions early in the design cycle. The modules are grouped into circuits (the subsystems) and displayed in an N x N matrix format. Feedback links, which indicate an iterative process, are minimized and only occur within a subsystem. Since there are no feedback links among the circuits, the circuits can be displayed in a multilevel format. Thus, a large amount of information is reduced to one or two displays which are stored for later retrieval and modification. The design manager and leaders of the design teams then have a visual display of the design problem and the intricate interactions among the different modules. The design manager could save a substantial

  15. DEMAID - A DESIGN MANAGER'S AID FOR INTELLIGENT DECOMPOSITION (MACINTOSH VERSION)

    NASA Technical Reports Server (NTRS)

    Rogers, J. L.

    1994-01-01

    Many engineering systems are large and multi-disciplinary. Before the design of new complex systems such as large space platforms can begin, the possible interactions among subsystems and their parts must be determined. Once this is completed the proposed system can be decomposed to identify its hierarchical structure. DeMAID (A Design Manager's Aid for Intelligent Decomposition) is a knowledge-based system for ordering the sequence of modules and identifying a possible multilevel structure for the design problem. DeMAID displays the modules in an N x N matrix format (called a design structure matrix) where a module is any process that requires input and generates an output. (Modules which generate an output but do not require an input, such as an initialization process, are also acceptable.) Although DeMAID requires an investment of time to generate and refine the list of modules for input, it could save a considerable amount of money and time in the total design process, particularly in new design problems where the ordering of the modules has not been defined. The decomposition of a complex design system into subsystems requires the judgement of the design manager. DeMAID reorders and groups the modules based on the links (interactions) among the modules, helping the design manager make decomposition decisions early in the design cycle. The modules are grouped into circuits (the subsystems) and displayed in an N x N matrix format. Feedback links, which indicate an iterative process, are minimized and only occur within a subsystem. Since there are no feedback links among the circuits, the circuits can be displayed in a multilevel format. Thus, a large amount of information is reduced to one or two displays which are stored for later retrieval and modification. The design manager and leaders of the design teams then have a visual display of the design problem and the intricate interactions among the different modules. The design manager could save a substantial

  16. Computer-aided Molecular Design of Compounds Targeting Histone Modifying Enzymes

    PubMed Central

    Andreoli, Federico; Del Rio, Alberto

    2015-01-01

    Growing evidences show that epigenetic mechanisms play crucial roles in the genesis and progression of many physiopathological processes. As a result, research in epigenetic grew at a fast pace in the last decade. In particular, the study of histone post-translational modifications encountered an extraordinary progression and many modifications have been characterized and associated to fundamental biological processes and pathological conditions. Histone modifications are the catalytic result of a large set of enzyme families that operate covalent modifications on specific residues at the histone tails. Taken together, these modifications elicit a complex and concerted processing that greatly contribute to the chromatin remodeling and may drive different pathological conditions, especially cancer. For this reason, several epigenetic targets are currently under validation for drug discovery purposes and different academic and industrial programs have been already launched to produce the first pre-clinical and clinical outcomes. In this scenario, computer-aided molecular design techniques are offering important tools, mainly as a consequence of the increasing structural information available for these targets. In this mini-review we will briefly discuss the most common types of known histone modifications and the corresponding operating enzymes by emphasizing the computer-aided molecular design approaches that can be of use to speed-up the efforts to generate new pharmaceutically relevant compounds. PMID:26082827

  17. Computer-aided Molecular Design of Compounds Targeting Histone Modifying Enzymes.

    PubMed

    Andreoli, Federico; Del Rio, Alberto

    2015-01-01

    Growing evidences show that epigenetic mechanisms play crucial roles in the genesis and progression of many physiopathological processes. As a result, research in epigenetic grew at a fast pace in the last decade. In particular, the study of histone post-translational modifications encountered an extraordinary progression and many modifications have been characterized and associated to fundamental biological processes and pathological conditions. Histone modifications are the catalytic result of a large set of enzyme families that operate covalent modifications on specific residues at the histone tails. Taken together, these modifications elicit a complex and concerted processing that greatly contribute to the chromatin remodeling and may drive different pathological conditions, especially cancer. For this reason, several epigenetic targets are currently under validation for drug discovery purposes and different academic and industrial programs have been already launched to produce the first pre-clinical and clinical outcomes. In this scenario, computer-aided molecular design techniques are offering important tools, mainly as a consequence of the increasing structural information available for these targets. In this mini-review we will briefly discuss the most common types of known histone modifications and the corresponding operating enzymes by emphasizing the computer-aided molecular design approaches that can be of use to speed-up the efforts to generate new pharmaceutically relevant compounds.

  18. Beliefs about AIDS, use of alcohol and drugs, and unprotected sex among Massachusetts adolescents.

    PubMed

    Hingson, R W; Strunin, L; Berlin, B M; Heeren, T

    1990-03-01

    In August 1988, 1,773 Massachusetts 16-19-year-olds were surveyed by telephone using anonymous random digit dialing; response rate 82 percent. Logistic regression tested whether alcohol and drug use, perceived susceptibility to human immunodeficiency virus (HIV), severity of HIV if infected, effectiveness of condoms in preventing infection, barriers to condom use, and behavioral cues such as exposure to media or personal communication about acquired immunodeficiency syndrome (AIDS) were independently related to condom use. Among sexually active respondents, (61 percent of those interviewed) 31 percent reported always using condoms. Respondents who believed condoms are effective in preventing HIV transmission and worried they can get AIDS were 3.1 and 1.8 times, respectively, more likely to use condoms all the time. Respondents who carried condoms and who had discussed AIDS with a physician were 2.7 and 1.7 times, respectively, more likely to use them. Those who believed condoms do not reduce sexual pleasure and would not be embarrassed if asked to use them were 3.1 and 2.4 times, respectively, more likely to use condoms. Teens who averaged five or more drinks daily or used marijuana in the previous month were 2.8 and 1.9 times, respectively, less likely to use condoms. Among respondents who drink and use drugs, 16 percent used condoms less often after drinking and 25 percent after drug use. Those counseling adolescents about HIV should assess and discuss beliefs outlined in the Health Belief Model, as well as their alcohol and drug use.

  19. 33 CFR 66.05-10 - State waters for private aids to navigation; designations; revisions, and revocations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false State waters for private aids to... Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-10 State waters for private aids to navigation; designations; revisions,...

  20. 33 CFR 66.05-10 - State waters for private aids to navigation; designations; revisions, and revocations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false State waters for private aids to... Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-10 State waters for private aids to navigation; designations; revisions,...

  1. 33 CFR 66.05-10 - State waters for private aids to navigation; designations; revisions, and revocations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false State waters for private aids to... Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-10 State waters for private aids to navigation; designations; revisions,...

  2. 33 CFR 66.05-100 - Designation of navigable waters as State waters for private aids to navigation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... as State waters for private aids to navigation. 66.05-100 Section 66.05-100 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-100 Designation of navigable waters as State waters for private aids...

  3. 33 CFR 66.05-100 - Designation of navigable waters as State waters for private aids to navigation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... as State waters for private aids to navigation. 66.05-100 Section 66.05-100 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-100 Designation of navigable waters as State waters for private aids...

  4. 33 CFR 66.05-10 - State waters for private aids to navigation; designations; revisions, and revocations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false State waters for private aids to... Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-10 State waters for private aids to navigation; designations; revisions,...

  5. 33 CFR 66.05-100 - Designation of navigable waters as State waters for private aids to navigation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... as State waters for private aids to navigation. 66.05-100 Section 66.05-100 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-100 Designation of navigable waters as State waters for private aids...

  6. 33 CFR 66.05-100 - Designation of navigable waters as State waters for private aids to navigation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... as State waters for private aids to navigation. 66.05-100 Section 66.05-100 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-100 Designation of navigable waters as State waters for private aids...

  7. 33 CFR 66.05-100 - Designation of navigable waters as State waters for private aids to navigation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... as State waters for private aids to navigation. 66.05-100 Section 66.05-100 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-100 Designation of navigable waters as State waters for private aids...

  8. 33 CFR 66.05-10 - State waters for private aids to navigation; designations; revisions, and revocations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false State waters for private aids to... Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION PRIVATE AIDS TO NAVIGATION State Aids to Navigation § 66.05-10 State waters for private aids to navigation; designations; revisions,...

  9. Designing a new generation of antidepressant drugs.

    PubMed

    Pinder, R M

    1997-01-01

    Although longer-term adaptive changes in receptor sensitivity may better explain the delayed onset of action of antidepressants, the mechanism based on acutely elevated noradrenaline (NA) and serotonin (5-HT) synaptic levels remains the basis for new drug design. The dual action concept, which postulates that effects on both NA and 5-HT are more advantageous than a selective action on serotonin reuptake (SSRI), has been used to design new antidepressants such as venlafaxine and mirtazapine. Both drugs enhance NA and 5-HT neurotransmission with little affinity for receptors mediating tricyclic-like side effects. Mirtazapine, the prototype noradrenergic and specific serotonergic antidepressant (NaSSA), specifically enhances 5-HT1 neurotransmission and blocks 5-HT2 and 5-HT3 receptors, and in contrast to venlafaxine lacks SSRI-like and adverse cardiovascular side effects. The unique pharmacological action of mirtazapine is a result of implementation of two concepts: dual action as a basis of efficacy combined with receptor-specific action as a basis of tolerability. PMID:9265946

  10. Drug design for neglected disease in Brazil.

    PubMed

    Giarolla, Jeanine; Ferreira, Elizabeth Igne

    2015-01-01

    Neglected tropical diseases (NTD) are a group of 17 diseases transmitted by virus, protozoa, helminthes and bacteria. These illnesses are responsible for millions of deaths per year, affecting mainly the poorest populations in the world. The therapeutic drugs available are obsolete, toxic, have questionable efficacy and there are reports of resistance. Therefore, the discovery of new, safe, effective and affordable active molecules is urgently needed. Considering that, the main purpose of this mini-review is to show the current scenario concerning drug design for neglected disease in Brazil. NTD are a very broad topic. Thus, we selected four infections for discussion: Chagas disease, leishmaniasis, malaria and tuberculosis. According to CNPq (National Counsel of Technological and Scientific Development) directories, there are many Brazilian groups studying these respective diseases. The papers published possess high quality and some of them, the most recent, are briefly discussed here. Medicinal chemistry approaches such as synthesis of novel series of molecules and biological activity evaluation, studies of structure-activity relationships (qualitative and quantitative), molecular modeling calculations and electrochemistry are some of the tools applied in the design of the compounds.

  11. Epidemiology of HIV/AIDS, hepatitis B, hepatitis C, and tuberculosis among minority injection drug users.

    PubMed Central

    Estrada, Antonio L.

    2002-01-01

    OBJECTIVE: This article reviews the literature on the impact of HIV/AIDS, hepatitis B and C viruses (HBV, HCV), and tuberculosis on minority drug injectors in the United States. OBSERVATIONS: Injection drug use is a key factor in the transmission of blood-borne pathogens, and HIV disease is exacerbated by tuberculosis infection. Minority drug injectors are disproportionately represented in the national statistics on these infections. Behavioral epidemiologic studies show that both injection-related risk factors years of injecting drugs, type of drug injected, direct and indirect sharing of injection paraphernalia) and sex-related risk factors (lack of condom use, multiple sexual partners, survival sex) are conducive to the spread of HIV, HBV, and HCV. CONCLUSIONS: Two issues must be addressed to halt the spread of HIV infection and hepatitis B and C. The capacity of syringe-exchange programs to refer participants to drug treatment programs and facilitate access to health and social services must be increased. Culturally appropriate behavioral interventions targeting risk behaviors among ethnic and racial minorities, especially women, must be developed and put in place. PMID:12435836

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

    ERIC Educational Resources Information Center

    Cheng, Wan-Lee

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

  13. Definition of Design Case Similarity Based on Physical Quantities and Terms for Engineering Design Aid

    NASA Astrophysics Data System (ADS)

    Murakami, Tamotsu; Shimamura, Jun; Nakajima, Naomasa

    This paper proposes computerized methods of case-based design aid using similarity and relevance between design cases. First, we introduce methods of describing and recording design cases and design modification cases by physical quantities and their calculations to represent physical phenomena and terms to explain them. Then, we introduce a quantity dimension space defined by nine fundamental and supplementary quantities in SI. In quantity dimension space, a distance between physical quantities is mathematically defined based on city-block distance, and then physical quantity similarity by dimension is defined using the physical quantity distance. Then, similarity between physical quantities is defined by combining the similarity by dimension and similarity of quantity calculation structures. Also, similarity between terms is defined by combining literal similarity and cooccurrence statistics. Finally, similarity between design (modification) cases is defined based on physical quantity similarity and term similarity. By using design case similarity, designers can retrieve and consult the similar or relevant cases to a new design problem in a design case library. Also, design modification knowledge such as “which physical quantity or design parameter should be modified to solve specific trouble” can be extracted by analyzing recorded design modification cases and clustering them using design (modification) case similarity. The proposed methods are implemented as a Lisp program and are examined through some examples.

  14. Predictive statistics and artificial intelligence in the U.S. National Cancer Institute's Drug Discovery Program for Cancer and AIDS.

    PubMed

    Weinstein, J N; Myers, T; Buolamwini, J; Raghavan, K; van Osdol, W; Licht, J; Viswanadhan, V N; Kohn, K W; Rubinstein, L V; Koutsoukos, A D

    1994-01-01

    The National Cancer Institute's drug discovery program screens more than 20,000 chemical compounds and natural products a year for activity against a panel of 60 tumor cell lines in vitro. The result is an information-rich database of patterns that form the basis for what we term an "information-intensive" approach to the process of drug discovery. The first step was a demonstration, both by statistical methods (including the program COMPARE) and by neural networks, that patterns of activity in the screen can be used to predict a compound's mechanism of action. Given this finding, the overall plan has been to develop three large matrices of information: the first (designated A) gives the pattern of activity for each compound tested against each cell line in the screen; the second (S) encodes any of a number of types of 2-D or 3-D structural motifs for each compound; the third (T) indicates each cell's expression of molecular targets (e.g., from 2-dimensional protein gel electrophoresis). Construction and updating of these matrices is an ongoing process. The matrices can be concatenated in various ways to test a variety of specific hypotheses about compounds screened, as well as to "prioritize" candidate compounds for testing. To aid in these efforts, we have developed the DISCOVERY program package, which integrates the matrix data for visual pattern recognition. The "information-intensive" approach summarized here in some senses serves to bridge the perceived gap between screening and structure-based drug design.

  15. PUZZLE - A program for computer-aided design of printed circuit artwork

    NASA Technical Reports Server (NTRS)

    Harrell, D. A. W.; Zane, R.

    1971-01-01

    Program assists in solving spacing problems encountered in printed circuit /PC/ design. It is intended to have maximum use for two-sided PC boards carrying integrated circuits, and also aids design of discrete component circuits.

  16. Improving radiation survey data using CADD/CAE (computer-aided design and drafting computer-aided engineering)

    SciTech Connect

    Palau, G.L.; Tarpinian, J.E.

    1987-01-01

    A new application of computer-aided design and drafting (CADD) and computer-aided engineering (CAE) at the Three Mile Island Unit 2 (TMI-2) cleanup is improving the quality of radiation survey data taken in the plant. The use of CADD/CAE-generated survey maps has increased both the accuracy of survey data and the capability to perform analyses with these data. In addition, health physics technician manhours and radiation exposure can be reduced in situations where the CADD/CAE-generated drawings are used for survey mapping.

  17. Designing and Implementing an Educational Program on AIDS for Minority Childbearing Women To Enhance AIDS Awareness.

    ERIC Educational Resources Information Center

    Nimphius, Gail M.

    Ignorance, misinformation, and a failure to personalize the risk for acquisition of the Acquired Immune Deficiency Syndrome (AIDS) virus has created a situation in which the incidence of Human Immunodeficiency Virus (HIV) seroprevalence among minority childbearing women in a Florida county is increasing. An increased incidence in this population…

  18. DeMAID/GA USER'S GUIDE Design Manager's Aid for Intelligent Decomposition with a Genetic Algorithm

    NASA Technical Reports Server (NTRS)

    Rogers, James L.

    1996-01-01

    Many companies are looking for new tools and techniques to aid a design manager in making decisions that can reduce the time and cost of a design cycle. One tool that is available to aid in this decision making process is the Design Manager's Aid for Intelligent Decomposition (DeMAID). Since the initial release of DEMAID in 1989, numerous enhancements have been added to aid the design manager in saving both cost and time in a design cycle. The key enhancement is a genetic algorithm (GA) and the enhanced version is called DeMAID/GA. The GA orders the sequence of design processes to minimize the cost and time to converge to a solution. These enhancements as well as the existing features of the original version of DEMAID are described. Two sample problems are used to show how these enhancements can be applied to improve the design cycle. This report serves as a user's guide for DeMAID/GA.

  19. Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance.

    PubMed

    Suwandecha, Tan; Wongpoowarak, Wibul; Srichana, Teerapol

    2016-01-01

    Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60 L/min. The mass median aerodynamic diameter was around 2.8-4 μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5-7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.

  20. Collagen interactions: Drug design and delivery.

    PubMed

    An, Bo; Lin, Yu-Shan; Brodsky, Barbara

    2016-02-01

    Collagen is a major component in a wide range of drug delivery systems and biomaterial applications. Its basic physical and structural properties, together with its low immunogenicity and natural turnover, are keys to its biocompatibility and effectiveness. In addition to its material properties, the collagen triple-helix interacts with a large number of molecules that trigger biological events. Collagen interactions with cell surface receptors regulate many cellular processes, while interactions with other ECM components are critical for matrix structure and remodeling. Collagen also interacts with enzymes involved in its biosynthesis and degradation, including matrix metalloproteinases. Over the past decade, much information has been gained about the nature and specificity of collagen interactions with its partners. These studies have defined collagen sequences responsible for binding and the high-resolution structures of triple-helical peptides bound to its natural binding partners. Strategies to target collagen interactions are already being developed, including the use of monoclonal antibodies to interfere with collagen fibril formation and the use of triple-helical peptides to direct liposomes to melanoma cells. The molecular information about collagen interactions will further serve as a foundation for computational studies to design small molecules that can interfere with specific interactions or target tumor cells. Intelligent control of collagen biological interactions within a material context will expand the effectiveness of collagen-based drug delivery.

  1. Health Emergency 2003: The Spread of Drug-Related AIDS and Hepatitis C among African American and Latinos. Health Emergency Series.

    ERIC Educational Resources Information Center

    Day, Dawn

    This report is the fifth in a series detailing the impact of the injection-related AIDS epidemic on African Americans and Latinos. Ten chapters include: (1) "Health Emergency: The Spread of AIDS among African Americans Who Inject Drugs"; (2) "Health Emergency: The Spread of AIDS Among Latinos Who Inject Drugs"; (3) "A Neglected Opportunity: Drug…

  2. Software Infrastructure for Computer-aided Drug Discovery and Development, a Practical Example with Guidelines.

    PubMed

    Moretti, Loris; Sartori, Luca

    2016-09-01

    In the field of Computer-Aided Drug Discovery and Development (CADDD) the proper software infrastructure is essential for everyday investigations. The creation of such an environment should be carefully planned and implemented with certain features in order to be productive and efficient. Here we describe a solution to integrate standard computational services into a functional unit that empowers modelling applications for drug discovery. This system allows users with various level of expertise to run in silico experiments automatically and without the burden of file formatting for different software, managing the actual computation, keeping track of the activities and graphical rendering of the structural outcomes. To showcase the potential of this approach, performances of five different docking programs on an Hiv-1 protease test set are presented. PMID:27546042

  3. Software Infrastructure for Computer-aided Drug Discovery and Development, a Practical Example with Guidelines.

    PubMed

    Moretti, Loris; Sartori, Luca

    2016-09-01

    In the field of Computer-Aided Drug Discovery and Development (CADDD) the proper software infrastructure is essential for everyday investigations. The creation of such an environment should be carefully planned and implemented with certain features in order to be productive and efficient. Here we describe a solution to integrate standard computational services into a functional unit that empowers modelling applications for drug discovery. This system allows users with various level of expertise to run in silico experiments automatically and without the burden of file formatting for different software, managing the actual computation, keeping track of the activities and graphical rendering of the structural outcomes. To showcase the potential of this approach, performances of five different docking programs on an Hiv-1 protease test set are presented.

  4. Stigma, social reciprocity and exclusion of HIV/AIDS patients with illicit drug histories: A study of Thai nurses' attitudes

    PubMed Central

    Chan, Kit Yee; Stoové, Mark A; Reidpath, Daniel D

    2008-01-01

    Background Stigma is a key barrier for the delivery of care to patients living with HIV/AIDS (PLWHA). In the Asia region, the HIV/AIDS epidemic has disproportionately affected socially marginalised groups, in particular, injecting drug users. The effect of the stigmatising attitudes towards injecting drug users on perceptions of PLWHA within the health care contexts has not been thoroughly explored, and typically neglected in terms of stigma intervention. Methods Semi-structured interviews were conducted with a group of twenty Thai trainee and qualified nurses. Drawing upon the idea of 'social reciprocity', this paper examines the constructions of injecting drug users and PLWHA by a group of Thai nurses. Narratives were explored with a focus on how participants' views concerning the high-risk behaviour of injecting drug use might influence their attitudes towards PLWHA. Results The analysis shows that active efforts were made by participants to separate their views of patients living with HIV/AIDS from injecting drug users. While the former were depicted as patients worthy of social support and inclusion, the latter were excluded on the basis that they were perceived as irresponsible 'social cheaters' who pose severe social and economic harm to the community. Absent in the narratives were references to wider socio-political and epidemiological factors related to drug use and needle sharing that expose injecting drug users to risk; these behaviours were constructed as individual choices, allowing HIV positive drug users to be blamed for their seropositive status. These attitudes could potentially have indirect negative implications on the nurses' opinions of patients living with HIV/AIDS more generally. Conclusion Decreasing the stigma associated with illicit drugs might play crucial role in improving attitudes towards patients living with HIV/AIDS. Providing health workers with a broader understanding of risk behaviours and redirecting government injecting drug

  5. Chemical delivery systems and soft drugs: Retrometabolic approaches of drug design

    PubMed Central

    Bhardwaj, Yashumati Ratan; Pareek, Ashutosh; Jain, Vivek; Kishore, Dharma

    2013-01-01

    Inclusion of metabolic considerations in the drug design process leads to significant development in the field of chemical drug targeting and the design of safer drugs during past few years which is a part of an approach now designated as Retro metabolic drug design (RMDD). This approach represents systematic methodologies that integrate structure–activity and structure–metabolism relationships and are aimed to design safe, locally active compounds with an improved therapeutic index. It embraces two distinct methods, chemical delivery systems and a soft drug approach. Present review recapitulates an impression of RMDD giving reflections on the chemical delivery system and the soft drug approach and provides a variety of examples to embody its concepts. Successful application of such design principles has already been applied to a number of marketed drugs like esmolol; loteprednol etc., and many other candidates like beta blockers, ACE inhibitors, alkylating agents, antimicrobials etc., are also under investigation. PMID:25161372

  6. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

    PubMed

    Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J

    2015-12-10

    The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel

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

    ERIC Educational Resources Information Center

    McGrann, Roy T. R.

    2006-01-01

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

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

    ERIC Educational Resources Information Center

    Gosman, A. D.; And Others

    1979-01-01

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

  9. Office of Student Financial Aid Quality Improvement Program: Design and Implementation Plan.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    The purpose and direction of the quality improvement program of the U.S. Department of Education's Office of Student Financial Aid (OSFA) are described. The improvement program was designed to develop a systematic approach to identify, measure, and correct errors in the student aid delivery system. Information is provided on the general approach…

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

    PubMed

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

    2015-07-01

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

  11. The management of endodontically treated teeth using a Computer-Aided Design and Computer-Assisted Manufacturing/Computer-Aided Design and Computer-Integrated Manufacturing system.

    PubMed

    Foerster, J G; von Gonten, A S; Robert, G H

    1999-01-01

    This article introduces a new approach for restoring endodontically treated posterior teeth. Significantly reduced natural tooth structure often remains not only because of previous restorative measures but also because of endodontic procedures. Cast restorations for these teeth are almost universally recommended. The exception to this is the rare instance in which only conservative endodontic access openings exist in teeth presenting with no former existing restorations. Typically, multiple clinical appointments are required to complete the final cast restoration. This article presents Computer-Aided Design and Computer-Assisted Manufacturing/Computer-Aided Design and Computer-Integrated Manufacturing applications for restorative dentistry that provide the necessary care in an expeditious manner.

  12. Predictable Restorative Work Flow for Computer-Aided Design/Computer-Aided Manufacture-Fabricated Ceramic Veneers Utilizing a Virtual Smile Design Principle.

    PubMed

    Lin, W S; Zandinejad, A; Metz, M J; Harris, B T; Morton, D

    2015-01-01

    The purpose of this case report was to present the use of a contemporary digital photograph-assisted virtual smile design principle, an intraoral digital impression, and computer-aided design/computer-aided manufacture-fabricated lithium disilicate ceramic veneers to treat a patient with esthetic needs in the maxillary anterior region. By using the proposed digital restorative work flow, this case report demonstrated an effective communication pathway between the patient, clinician, and dental laboratory technician. Effective communication can help to achieve a more predictable and satisfactory esthetic outcome.

  13. 23 CFR 636.104 - Does this part apply to all Federal-aid design-build projects?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Federal-aid design-build projects? The provisions of this part apply to all Federal-aid design-build... 23 Highways 1 2010-04-01 2010-04-01 false Does this part apply to all Federal-aid design-build projects? 636.104 Section 636.104 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF...

  14. 23 CFR 636.104 - Does this part apply to all Federal-aid design-build projects?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Federal-aid design-build projects? The provisions of this part apply to all Federal-aid design-build... 23 Highways 1 2013-04-01 2013-04-01 false Does this part apply to all Federal-aid design-build projects? 636.104 Section 636.104 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF...

  15. 23 CFR 636.104 - Does this part apply to all Federal-aid design-build projects?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Federal-aid design-build projects? The provisions of this part apply to all Federal-aid design-build... 23 Highways 1 2012-04-01 2012-04-01 false Does this part apply to all Federal-aid design-build projects? 636.104 Section 636.104 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF...

  16. 23 CFR 636.104 - Does this part apply to all Federal-aid design-build projects?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Federal-aid design-build projects? The provisions of this part apply to all Federal-aid design-build... 23 Highways 1 2011-04-01 2011-04-01 false Does this part apply to all Federal-aid design-build projects? 636.104 Section 636.104 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF...

  17. 23 CFR 636.104 - Does this part apply to all Federal-aid design-build projects?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Federal-aid design-build projects? The provisions of this part apply to all Federal-aid design-build... 23 Highways 1 2014-04-01 2014-04-01 false Does this part apply to all Federal-aid design-build projects? 636.104 Section 636.104 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF...

  18. Molecular Rift: Virtual Reality for Drug Designers.

    PubMed

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

    2015-11-23

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

  19. Molecular Rift: Virtual Reality for Drug Designers.

    PubMed

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

    2015-11-23

    Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate physical presence in the real world--a virtual reality. This is relevant to drug discovery since molecular models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Molecular Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for standard input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Molecular Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chemistry and education. Molecular Rift is open source and can be downloaded from GitHub. PMID:26558887

  20. Computer-Aided Engineering of Batteries for Designing Better Li-Ion Batteries (Presentation)

    SciTech Connect

    Pesaran, A.; Kim, G. H.; Smith, K.; Lee, K. J.; Santhanagopalan, S.

    2012-02-01

    This presentation describes the current status of the DOE's Energy Storage R and D program, including modeling and design tools and the Computer-Aided Engineering for Automotive Batteries (CAEBAT) program.

  1. Computer aided design of microcircuits. Citations from the NTIS data base

    NASA Astrophysics Data System (ADS)

    Reed, W. E.

    1980-09-01

    Government sponsored research covering the computer aided design, modeling, layout, and packaging of integrated and other microelectronic circuits are cited. Computer programs and the use of computer graphics are included.

  2. Implant-Assisted Intrathecal Magnetic Drug Targeting to Aid in Therapeutic Nanoparticle Localization for Potential Treatment of Central Nervous System Disorders.

    PubMed

    Lueshen, Eric; Venugopal, Indu; Soni, Tejen; Alaraj, Ali; Linninger, Andreas

    2015-02-01

    There is an ongoing struggle to develop efficient drug delivery and targeting methods within the central nervous system. One technique known as intrathecal drug delivery, involves direct drug infusion into the spinal canal and has become standard practice for treating many central nervous system diseases due to reduced systemic toxicity from the drug bypassing the blood-brain barrier. Although intrathecal drug delivery boasts the advantage of reduced systemic toxicity compared to oral and intravenous drug delivery techniques, current intrathecal delivery protocols lack a means of sufficient drug targeting at specific locations of interest within the central nervous system. We previously proposed the method of intrathecal magnetic drug targeting in order to overcome the limited targeting capabilities of standard intrathecal drug delivery protocols, while simultaneously reducing the systemic toxicity as well as the amount of drug required to produce a therapeutic effect. Building off of our previous work, this paper presents the concept of implant-assisted intrathecal magnetic drug targeting. Ferritic stainless steel implants were incorporated within the subarachnoid space of our in vitro human spine model, and the targeting magnet was placed at a physiological distance away from the model and implant to mimic the distance between the epidermis and spinal canal. Computer simulations were performed to optimize implant design for generating high gradient magnetic fields and to study how these fields may aid in therapeutic nanoparticle localization. Experiments aiming to determine the effects of different magnetically-susceptible implants placed within an external magnetic field on the targeting efficiency of gold-coated magnetite nanoparticles were then performed on our in vitro human spine model. Our results indicate that implant-assisted intrathecal magnetic drug targeting is an excellent supplementary technique to further enhance the targeting capabilities of our

  3. Analytical Design Package (ADP2): A computer aided engineering tool for aircraft transparency design

    NASA Technical Reports Server (NTRS)

    Wuerer, J. E.; Gran, M.; Held, T. W.

    1994-01-01

    The Analytical Design Package (ADP2) is being developed as a part of the Air Force Frameless Transparency Program (FTP). ADP2 is an integrated design tool consisting of existing analysis codes and Computer Aided Engineering (CAE) software. The objective of the ADP2 is to develop and confirm an integrated design methodology for frameless transparencies, related aircraft interfaces, and their corresponding tooling. The application of this methodology will generate high confidence for achieving a qualified part prior to mold fabrication. ADP2 is a customized integration of analysis codes, CAE software, and material databases. The primary CAE integration tool for the ADP2 is P3/PATRAN, a commercial-off-the-shelf (COTS) software tool. The open architecture of P3/PATRAN allows customized installations with different applications modules for specific site requirements. Integration of material databases allows the engineer to select a material, and those material properties are automatically called into the relevant analysis code. The ADP2 materials database will be composed of four independent schemas: CAE Design, Processing, Testing, and Logistics Support. The design of ADP2 places major emphasis on the seamless integration of CAE and analysis modules with a single intuitive graphical interface. This tool is being designed to serve and be used by an entire project team, i.e., analysts, designers, materials experts, and managers. The final version of the software will be delivered to the Air Force in Jan. 1994. The Analytical Design Package (ADP2) will then be ready for transfer to industry. The package will be capable of a wide range of design and manufacturing applications.

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

    PubMed Central

    Baroudi, Kusai; Ibraheem, Shukran Nasser

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

    The use of bi-layered all-ceramic crowns has continuously grown since the introduction of computer-aided design/computer-aided manufacturing (CAD/CAM) zirconia cores. Unfortunately, despite the outstanding mechanical properties of zirconia, problems related to porcelain cracking or chipping remain. One of the reasons for this is that ceramic copings are usually milled to uniform thicknesses of 0.3-0.6 mm around the whole tooth preparation. This may not provide uniform thickness or appropriate support for the veneering porcelain. To prevent these problems, the dual-scan technique demonstrates an alternative that allows the restorative team to customize zirconia CAD/CAM frameworks with adequate porcelain thickness and support in a simple manner. PMID:24966718

  6. Computer-Aided Design Of Turbine Blades And Vanes

    NASA Technical Reports Server (NTRS)

    Hsu, Wayne Q.

    1988-01-01

    Quasi-three-dimensional method for determining aerothermodynamic configuration of turbine uses computer-interactive analysis and design and computer-interactive graphics. Design procedure executed rapidly so designer easily repeats it to arrive at best performance, size, structural integrity, and engine life. Sequence of events in aerothermodynamic analysis and design starts with engine-balance equations and ends with boundary-layer analysis and viscous-flow calculations. Analysis-and-design procedure interactive and iterative throughout.

  7. A Qualitative Study of Underutilization of the AIDS Drug Assistance Program

    PubMed Central

    Olson, Kristin M.; Godwin, Noah C.; Wilkins, Sara Anne; Mugavero, Michael J.; Moneyham, Linda D.; Slater, Larry Z.; Raper, James L.

    2014-01-01

    In our previous work, we demonstrated underutilization of the AIDS Drug Assistance Program (ADAP) at an HIV clinic in Alabama. In order to understand barriers and facilitators to utilization of ADAP, we conducted focus groups of ADAP enrollees. Focus groups were stratified by sex, race, and historical medication possession ratio as a measure of program utilization. We grouped factors according to the social-ecological model. We found that multiple levels of influence, including patient and clinic-related factors, influenced utilization of antiretroviral medications. Patients introduced issues that illustrated high-priority needs for ADAP policy and implementation, suggesting that in order to improve ADAP utilization, the following issues must be addressed: patient transportation, ADAP medication refill schedules and procedures, mailing of medications, and the ADAP recertification process. These findings can inform a strategy of approaches to improve ADAP utilization, which may have widespread implications for ADAP programs across the United States. PMID:24503498

  8. [Vulnerability to sexually transmitted diseases/AIDS and use of psychoactive drugs by truck drivers].

    PubMed

    Masson, Valéria Aparecida; Monteiro, Maria Inês

    2010-01-01

    A cross-sectional epidemiological descriptive study with the purpose of identify the demographic characteristics, health aspects and life style, vulnerability to Sexually Transmitted Diseases/AIDS amongst long distance truck drivers were applied to 50 drivers from supply center of Campinas (fruit, vegetable, product wholesale market). The outcomes showed that almost all drivers interviewed were men, the majority were married, had kids, low study level and fewer than 40 years old. 70% reported abuse psychoactive drugs. The majority was aware of the importance of using condoms with casual partners; 94% reported relationship with casual partners and just 6% never used condoms. Although the small sample analyzed, the results suggests that must be implemented health promotion actions and illness prevention public politics, including the development of customized educational interventions with in this professional group. PMID:20339759

  9. [Vulnerability to sexually transmitted diseases/AIDS and use of psychoactive drugs by truck drivers].

    PubMed

    Masson, Valéria Aparecida; Monteiro, Maria Inês

    2010-01-01

    A cross-sectional epidemiological descriptive study with the purpose of identify the demographic characteristics, health aspects and life style, vulnerability to Sexually Transmitted Diseases/AIDS amongst long distance truck drivers were applied to 50 drivers from supply center of Campinas (fruit, vegetable, product wholesale market). The outcomes showed that almost all drivers interviewed were men, the majority were married, had kids, low study level and fewer than 40 years old. 70% reported abuse psychoactive drugs. The majority was aware of the importance of using condoms with casual partners; 94% reported relationship with casual partners and just 6% never used condoms. Although the small sample analyzed, the results suggests that must be implemented health promotion actions and illness prevention public politics, including the development of customized educational interventions with in this professional group.

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

    NASA Astrophysics Data System (ADS)

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

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

  11. NREL Software Aids Offshore Wind Turbine Designs (Fact Sheet)

    SciTech Connect

    Not Available

    2013-10-01

    NREL researchers are supporting offshore wind power development with computer models that allow detailed analyses of both fixed and floating offshore wind turbines. While existing computer-aided engineering (CAE) models can simulate the conditions and stresses that a land-based wind turbine experiences over its lifetime, offshore turbines require the additional considerations of variations in water depth, soil type, and wind and wave severity, which also necessitate the use of a variety of support-structure types. NREL's core wind CAE tool, FAST, models the additional effects of incident waves, sea currents, and the foundation dynamics of the support structures.

  12. Current pharmaceutical design on adhesive based transdermal drug delivery systems.

    PubMed

    Ghosh, Animesh; Banerjee, Subham; Kaity, Santanu; Wong, Tin W

    2015-01-01

    Drug-in-adhesive transdermal drug delivery matrix exploits intimate contact of the carrier with stratum corneum, the principal skin barrier to drug transport, to deliver the actives across the skin and into the systemic circulation. The main application challenges of drug-in-adhesive matrix lie in the physicochemical properties of skin varying with age, gender, ethnicity, health and environmental condition of patients. This in turn poses difficulty to design a universal formulation to meet the intended adhesiveness, drug release and drug permeation performances. This review focuses on pressure-sensitive adhesives, and their adhesiveness and drug release/permeation modulation mechanisms as a function of adhesive molecular structure and formulation attributes. It discusses approaches to modulate adhesive tackiness, strength, elasticity, hydrophilicity, molecular suspension capability and swelling capacity, which contribute to the net effect of adhesive on skin bonding, drug release and drug permeation. PMID:25925119

  13. Current pharmaceutical design on adhesive based transdermal drug delivery systems.

    PubMed

    Ghosh, Animesh; Banerjee, Subham; Kaity, Santanu; Wong, Tin W

    2015-01-01

    Drug-in-adhesive transdermal drug delivery matrix exploits intimate contact of the carrier with stratum corneum, the principal skin barrier to drug transport, to deliver the actives across the skin and into the systemic circulation. The main application challenges of drug-in-adhesive matrix lie in the physicochemical properties of skin varying with age, gender, ethnicity, health and environmental condition of patients. This in turn poses difficulty to design a universal formulation to meet the intended adhesiveness, drug release and drug permeation performances. This review focuses on pressure-sensitive adhesives, and their adhesiveness and drug release/permeation modulation mechanisms as a function of adhesive molecular structure and formulation attributes. It discusses approaches to modulate adhesive tackiness, strength, elasticity, hydrophilicity, molecular suspension capability and swelling capacity, which contribute to the net effect of adhesive on skin bonding, drug release and drug permeation.

  14. Organic carbamates in drug design and medicinal chemistry.

    PubMed

    Ghosh, Arun K; Brindisi, Margherita

    2015-04-01

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

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

    PubMed

    Musselman, Megan E; Hampton, Jeremy P

    2014-07-01

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

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

    PubMed

    Musselman, Megan E; Hampton, Jeremy P

    2014-07-01

    Synthetic, or "designer" drugs, are created by manipulating the chemical structures of other psychoactive drugs so that the resulting product is structurally similar but not identical to illegal psychoactive drugs. Originally developed in the 1960s as a way to evade existing drug laws, the use of designer drugs has increased dramatically over the past few years. These drugs are deceptively packaged as "research chemicals," "incense," "bath salts," or "plant food," among other names, with labels that may contain warnings such as "not for human consumption" or "not for sale to minors." The clinical effects of most new designer drugs can be described as either hallucinogenic, stimulant, or opioid-like. They may also have a combination of these effects due to designer side-chain substitutions. The easy accessibility and rapid emergence of new designer drugs have created challenges for health care providers when treating patients presenting with acute toxicity from these substances, many of which can produce significant and/or life-threatening adverse effects. Moreover, the health care provider has no way to verify the contents and/or potency of the agent ingested because it can vary between packages and distributors. Therefore, a thorough knowledge of the available designer drugs, common signs and symptoms of toxicity associated with these agents, and potential effective treatment modalities are essential to appropriately manage these patients. PMID:24710806

  17. Creation of Anatomically Accurate Computer-Aided Design (CAD) Solid Models from Medical Images

    NASA Technical Reports Server (NTRS)

    Stewart, John E.; Graham, R. Scott; Samareh, Jamshid A.; Oberlander, Eric J.; Broaddus, William C.

    1999-01-01

    Most surgical instrumentation and implants used in the world today are designed with sophisticated Computer-Aided Design (CAD)/Computer-Aided Manufacturing (CAM) software. This software automates the mechanical development of a product from its conceptual design through manufacturing. CAD software also provides a means of manipulating solid models prior to Finite Element Modeling (FEM). Few surgical products are designed in conjunction with accurate CAD models of human anatomy because of the difficulty with which these models are created. We have developed a novel technique that creates anatomically accurate, patient specific CAD solids from medical images in a matter of minutes.

  18. Computer aided optimal design of space reflectors and radiation concentrators

    NASA Astrophysics Data System (ADS)

    Saprykin, Oleg A.; Spirochkin, Yuriy K.; Kinelev, Vladimir G.; Sulimov, Valeriy D.

    1998-06-01

    The goal of space radiation receiver design is achievement of its maximal reflecting properties under some technological and financial restrictions. Optimal design problems of this type are characterized by nonconvex nondifferentiable objective functions. A numerical technique for optimal design of the structures and an applied software REFLEX under development are proposed.

  19. Integration and utilization of different visualization methods and devices in a structure-based drug design process

    NASA Astrophysics Data System (ADS)

    Grohn, Matti T.; Nyronen, Tommi N.

    2003-05-01

    Molecular visualization techniques are used in various stages in the computer-aided drug design process. Here, we report on utilization of a four wall immersive virtual room in the visualization of protein - drug complexes. The advantage of a virtual room compared to desktop graphics is that it provides a high-resolution large field of view, helping the observers of the visualization to dissect the individual important structural features more easily than while using only conventional molecular graphics visualizations.

  20. CFD Aided Design and Optimization of Francis Turbine Runners

    NASA Astrophysics Data System (ADS)

    Ayancik, Fatma; Demirel, Gizem; Celebioglu, Kutay; Acar, Erdem; Aradag, Selin; ETU Hydro Research Center Team

    2014-11-01

    Francis turbines are commonly used for hydroelectric power plants with their wide range of flow rate and head values. They are composed of five main components and they generate energy with the help of the runner connected to the generator. Therefore, runner is the most important part of a Francis turbine. All components of turbines are linked and they are designed to maximize the turbine efficiency. The dimensions of the runner vary depending on the design discharge, head and the speed of the rotor of the generators. In this study, a design methodology is developed to design turbine runners with the help of computational fluid dynamics and is applied to the runner design of three different hydroelectric power plant turbines. Multi objective design optimization is also performed and the response surfaces are investigated to obtain maximum turbine efficiency and cavitation free design. This study is financially supported by Turkish Ministry of Development.

  1. Impact of Participatory Design for Drug-Drug Interaction Alerts. A Comparison Study Between Two Interfaces.

    PubMed

    Luna, Daniel; Otero, Carlos; Risk, Marcelo; Stanziola, Enrique; González Bernaldo de Quirós, Fernán

    2016-01-01

    Decision support systems for alert drug-drug interactions have been shown as valid strategy to reduce medical error. Even so the use of these systems has not been as expected, probably due to the lack of a suitable design. This study compares two interfaces, one of them developed using participatory design techniques (based on user centered design processes). This work showed that the use of these techniques improves satisfaction, effectiveness and efficiency in an alert system for drug-drug interactions, a fact that was evident in specific situations such as the decrease of errors to meet the specified task, the time, the workload optimization and users overall satisfaction with the system.

  2. Modeling HIV/AIDS Drug Price Determinants in Brazil: Is Generic Competition a Myth?

    PubMed Central

    Meiners, Constance; Sagaon-Teyssier, Luis; Hasenclever, Lia; Moatti, Jean-Paul

    2011-01-01

    Background Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care. Methods and Findings Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition. Significance In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies. PMID:21858138

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

    PubMed Central

    Mukherjee, Avinaba; Sadhukhan, Gobinda Chandra

    2016-01-01

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

  4. Current and emerging opportunities for molecular simulations in structure-based drug design

    PubMed Central

    Michel, Julien

    2014-01-01

    An overview of the current capabilities and limitations of molecular simulation of biomolecular complexes in the context of computer-aided drug design is provided. Steady improvements in computer hardware coupled with more refined representations of energetics are leading to a new appreciation of the driving forces of molecular recognition. Molecular simulations are poised to more frequently guide the interpretation of biophysical measurements of biomolecular complexes. Ligand design strategies emerge from detailed analyses of computed structural ensembles. The feasibility of routine applications to ligand optimization problems hinges upon successful extensive large scale validation studies and the development of protocols to intelligently automate computations. PMID:24469595

  5. Coffee shops and clinics: the give and take of doing HIV/AIDS research with injecting drug users.

    PubMed

    Marsh, A; Loxley, W

    1992-06-01

    We discuss recruiting and interviewing injecting drug users and using research as health promotion in the context of collecting information related to human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) from a convenience sample of 200 injecting drug users, half in treatment and half not, in 1989 and 1990 in Perth, Western Australia. A variety of recruiting methods were used including advertising, referral by agency staff, 'snowballing' and approaches to personal contacts and others known to inject by the interviewer. Snowballing and personal contacts were the most successful means of recruiting those not in treatment, while advertising was comparatively unsuccessful with this group because of the importance of establishing the credibility of the study and the interviewer among injecting drug users before they will volunteer to be involved. The promotion of behavioural risk reduction among respondents during the interview is detailed. We argue that the traditionally rigid separation between research and intervention is inappropriate in the HIV/AIDS context. When lives are potentially at stake, any contact with injecting drug users, especially those not in treatment (where may receive HIV/AIDS education), must be used as an HIV/AIDS prevention opportunity, and the interview is an ideal opportunity. The employment of research as community intervention is also discussed. PMID:1391161

  6. Black-White Disparities in HIV/AIDS:The Role of Drug Policy and the Corrections System

    PubMed Central

    Blankenship, Kim M.; Smoyer, Amy B.; Bray, Sarah J.; Mattocks, Kristin

    2006-01-01

    African Americans in the United States are disproportionately affected by HIV/AIDS. We focus in this paper on the structural and contextual sources of HIV/AIDS risk, and suggest that among the most important of these sources are drug policy and the corrections system. In particular, high rates of exposure to the corrections system (including incarceration, probation, and parole) spurred in large part by federal and state governments’ self-styled war on drugs in the United States, have disproportionately affected African Americans. We review a wide range of research literature to suggest how exposure to the corrections system may affect the HIV/AIDS related risks of drug users in general, and the disproportionate HIV risk faced by African Americans in particular. We then discuss the implications of the information reviewed for structural interventions to address African American HIV-related risk. Future research must further our understanding of the relations among drug policy, corrections, and race-based disparities in HIV/AIDS. PMID:16327113

  7. Computer-aided design tools for economical MEMS fabrication processes

    NASA Astrophysics Data System (ADS)

    Schneider, Christian; Priebe, Andreas; Brueck, Rainer; Hahn, Kai

    1999-03-01

    Since the early 70s when microsystem technology was first introduce an enormous market for MST-products has been developed. Airbag sensors, micro pumps, ink jet nozzles etc. and the market is just about to start up. Establishing these products for a reasonable price requires mass production. Meanwhile, also computer-based design-tools have been developed in order to reduce the expenses for MST-design. In contrast to other physical design processes like e.g. in micro electronics, MEMS physical design is characterized by the fact that each product requires a tailored sequence of fabrication steps, usually selected from a variety of processing alternatives. The selection from these alternatives is based on economical constraints. Therefore, the design has a strong influence on the money and time spent to take an MST-product to market.

  8. CFD Aided Design and Production of Hydraulic Turbines

    NASA Astrophysics Data System (ADS)

    Kaplan, Alper; Cetinturk, Huseyin; Demirel, Gizem; Ayli, Ece; Celebioglu, Kutay; Aradag, Selin; ETU Hydro Research Center Team

    2014-11-01

    Hydraulic turbines are turbo machines which produce electricity from hydraulic energy. Francis type turbines are the most common one in use today. The design of these turbines requires high engineering effort since each turbine is tailor made due to different head and discharge. Therefore each component of the turbine is designed specifically. During the last decades, Computational Fluid Dynamics (CFD) has become very useful tool to predict hydraulic machinery performance and save time and money for designers. This paper describes a design methodology to optimize a Francis turbine by integrating theoretical and experimental fundamentals of hydraulic machines and commercial CFD codes. Specific turbines are designed and manufactured with the help of a collaborative CFD/CAD/CAM methodology based on computational fluid dynamics and five-axis machining for hydraulic electric power plants. The details are presented in this study. This study is financially supported by Turkish Ministry of Development.

  9. Aiding Design of Wave Energy Converters via Computational Simulations

    NASA Astrophysics Data System (ADS)

    Jebeli Aqdam, Hejar; Ahmadi, Babak; Raessi, Mehdi; Tootkaboni, Mazdak

    2015-11-01

    With the increasing interest in renewable energy sources, wave energy converters will continue to gain attention as a viable alternative to current electricity production methods. It is therefore crucial to develop computational tools for the design and analysis of wave energy converters. A successful design requires balance between the design performance and cost. Here an analytical solution is used for the approximate analysis of interactions between a flap-type wave energy converter (WEC) and waves. The method is verified using other flow solvers and experimental test cases. Then the model is used in conjunction with a powerful heuristic optimization engine, Charged System Search (CSS) to explore the WEC design space. CSS is inspired by charged particles behavior. It searches the design space by considering candidate answers as charged particles and moving them based on the Coulomb's laws of electrostatics and Newton's laws of motion to find the global optimum. Finally the impacts of changes in different design parameters on the power takeout of the superior WEC designs are investigated. National Science Foundation, CBET-1236462.

  10. Improved plug valve computer-aided design of plug element

    SciTech Connect

    Wordin, J.J.

    1990-02-01

    The purpose of this document is to present derivations of equations for the design of a plug valve and to present a computer program which performs the design calculations based on the derivations. The valve is based on a plug formed from a tractrix of revolution called a pseudosphere. It is of interest to be able to calculate various parameters for the plug for design purposes. For example, the surface area, volume, and center of gravity are important to determine friction and wear of the valve. A computer program in BASIC has been written to perform the design calculations. The appendix contains a computer program listing and verifications of results using approximation methods. A sample run is included along with necessary computer commands to run the program. 1 fig.

  11. WASTE REDUCTION USING COMPUTER-AIDED DESIGN TOOLS

    EPA Science Inventory

    Growing environmental concerns have spurred considerable interest in pollution prevention. In most instances, pollution prevention involves introducing radical changes to the design of processes so that waste generation is minimized.
    Process simulators can be effective tools i...

  12. Computer-Aided Apparel Design in University Curricula.

    ERIC Educational Resources Information Center

    Belleau, Bonnie D.; Bourgeois, Elva B.

    1991-01-01

    As computer-assisted design (CAD) become an integral part of the fashion industry, universities must integrate CAD into the apparel curriculum. Louisiana State University's curriculum enables students to collaborate in CAD problem solving with industry personnel. (SK)

  13. Computer-aided space shuttle orbiter wing design study

    NASA Technical Reports Server (NTRS)

    Phillips, W. P.; Decker, J. P.; Rau, T. R.; Glatt, C. R.

    1974-01-01

    An analytical and experimental investigation has been made to provide a space shuttle orbiter wing design that met the guideline requirements of landing performance, stability, and hypersonic trim for a specified center-of-gravity envelope. The analytical study was facilitated by the use of the Optimal Design Integration system (ODIN) and the experimental part of the investigation was conducted in the Langley low-turbulence pressure tunnel and the Langley continuous-flow hypersonic tunnel.

  14. Drug Guru: a computer software program for drug design using medicinal chemistry rules.

    PubMed

    Stewart, Kent D; Shiroda, Melisa; James, Craig A

    2006-10-15

    Drug Guru (drug generation using rules) is a new web-based computer software program for medicinal chemists that applies a set of transformations, that is, rules, to an input structure. The transformations correspond to medicinal chemistry design rules-of-thumb taken from the historical lore of drug discovery programs. The output of the program is a list of target analogs that can be evaluated for possible future synthesis. A discussion of the features of the program is followed by an example of the software applied to sildenafil (Viagra) in generating ideas for target analogs for phosphodiesterase inhibition. Comparison with other computer-assisted drug design software is given.

  15. Computer-aided identification of potential TYK2 inhibitors from drug database

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Li, Jianzong; Huang, Zhixin; Wang, Haiyang; Luo, Hao; Wang, Xin; Zhou, Nan; Wu, Chuanfang; Bao, Jinku

    2016-10-01

    TYK2 is a member of JAKs family protein tyrosine kinase activated in response to various cytokines. It plays a crucial role in transducing signals downstream of various cytokine receptors, which are involved in proinflammatory responses associated with immunological diseases. Thus, the study of selective TYK2 inhibitors is one of the most popular fields in anti-inflammation drug development. Herein, we adopted molecular docking, molecular dynamics simulation and MM-PBSA binding free energy calculation to screen potential TYK2-selective inhibitors from ZINC Drug Database. Finally, three small molecule drugs ZINC12503271 (Gemifloxacin), ZINC05844792 (Nebivolol) and ZINC00537805 (Glyburide) were selected as potential TYK2-selective inhibitors. Compared to known inhibitor 2,6-dichloro-N-{2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}benzamide, these three candidates had better Grid score and Amber score from molecular docking and preferable results from binding free energy calculation as well. What's more, the ATP-binding site and A-loop motif had been identified to play key roles in TYK2-targeted inhibitor discovery. It is expected that our study will pave the way for the design of potent TYK2 inhibitors of new drugs to treat a wide variety of immunological diseases such as inflammatory diseases, multiple sclerosis, psoriasis inflammatory bowel disease (IBD) and so on.

  16. Laser imaging and computer-aided design and computer-aided manufacture in prosthetics and orthotics.

    PubMed

    Spaeth, John P

    2006-02-01

    Although Hanger Orthopedic Group, Inc., has been developing clinical protocols for its INSIGNIA scanner for more than 2 years, there are many applications that are currently in development and will be released over the next 2-year period after this publication. It is the goal of Hanger Orthopedic Group, Inc., to replace all plaster casting procedures with the laser scan and move toward a paperless environment where all images and documents are passed through its virtual network. INSIGNIA currently has five major production centers throughout the United States, which support more than 600 INSIGNIA certified clinicians. These clinicians staff more than 600 clinics in North America, all under the Hanger company name. The central fabrication service and the central design center processes hundreds of shapes per day (Fig. 27). So that any clinician in the field can use the expertise of the central designers and central fabricators to help with overflow or problems they might be having, the network that exists within Hanger is tied together and enhanced by INSIGNIA. Through virtual modification and centralization of these services, each patient receives the virtual collaboration of several clinicians with a total of years of experience. INSIGNIA has enhanced the patient experience. The enhancement is not only in removing the plaster from the process, but also in exposing each patient to the team of prosthetic experts working collaboratively behind the scenes. The rehabilitation industry continues to be bombarded with compliance paperwork and justifications. The INSIGNIA scan and resulting measurement reports give inherent strength to justifications based on volume change, surgical revisions, or tissue change. The files are kept in a data warehouse where they are vaulted and preserved presumably forever. Also, any of the shape graphics or measurement instruments can be printed into a discrete report that can become part of the patient's permanent record. Many physicians

  17. Accuracy of different types of computer-aided design/computer-aided manufacturing surgical guides for dental implant placement

    PubMed Central

    Geng, Wei; Liu, Changying; Su, Yucheng; Li, Jun; Zhou, Yanmin

    2015-01-01

    Purpose: To evaluate the clinical outcomes of implants placed using different types of computer-aided design/computer-aided manufacturing (CAD/CAM) surgical guides, including partially guided and totally guided templates, and determine the accuracy of these guides Materials and methods: In total, 111 implants were placed in 24 patients using CAD/CAM surgical guides. After implant insertion, the positions and angulations of the placed implants relative to those of the planned ones were determined using special software that matched pre- and postoperative computed tomography (CT) images, and deviations were calculated and compared between the different guides and templates. Results: The mean angular deviations were 1.72 ± 1.67 and 2.71 ± 2.58, the mean deviations in position at the neck were 0.27 ± 0.24 and 0.69 ± 0.66 mm, the mean deviations in position at the apex were 0.37 ± 0.35 and 0.94 ± 0.75 mm, and the mean depth deviations were 0.32 ± 0.32 and 0.51 ± 0.48 mm with tooth- and mucosa-supported stereolithographic guides, respectively (P < .05 for all). The mean distance deviations when partially guided (29 implants) and totally guided templates (30 implants) were used were 0.54 ± 0.50 mm and 0.89 ± 0.78 mm, respectively, at the neck and 1.10 ± 0.85 mm and 0.81 ± 0.64 mm, respectively, at the apex, with corresponding mean angular deviations of 2.56 ± 2.23° and 2.90 ± 3.0° (P > .05 for all). Conclusions: Tooth-supported surgical guides may be more accurate than mucosa-supported guides, while both partially and totally guided templates can simplify surgery and aid in optimal implant placement. PMID:26309497

  18. Nanofibers based antibacterial drug design, delivery and applications.

    PubMed

    Ulubayram, Kezban; Calamak, Semih; Shahbazi, Reza; Eroglu, Ipek

    2015-01-01

    Infections caused by microorganisms like bacteria, fungi, etc. are the main obstacle in healing processes. Conventional antibacterial administration routes can be listed as oral, intravenous/intramuscular, topical and inhalation. These kinds of drug administrations are faced with critical vital issues such as; more rapid delivery of the drug than intended which can result in bacterial resistance, dose related systemic toxicity, tissue irritation and finally delayed healing process that need to be tackled. Recently, studies have been focused on new drug delivery systems, overcoming resistance and toxicological problems and finally localizing the molecules at the site of action in a proper dose. In this regard, many nanotechnological approaches such as nanoparticulate therapeutic systems have been developed to address accompanying problems mentioned above. Among them, drug loaded electrospun nanofibers propose main advantages like controlled drug delivery, high drug loading capacity, high encapsulation efficiency, simultaneous delivery of multiple drugs, ease of production and cost effectiveness for pharmaceutical and biomedical applications. Therefore, some particular attention has been devoted to the design of electrospun nanofibers as promising antibacterial drug carrier systems. A variety of antibacterials e.g., biocides, antibiotics, quaternary ammonium salts, triclosan, metallic nanoparticles (silver, titanium dioxide, and zinc oxide) and antibacterial polymers (chitosan, polyethyleneimine, etc.) have been impregnated by various techniques into nanofibers that exhibit strong antibacterial activity in standard assays. This review highlights the design and delivery of antibacterial drug loaded nanofibers with particular focus on their function in the fields of drug delivery, wound healing, tissue engineering, cosmetics and other biomedical applications.

  19. Nanofibers based antibacterial drug design, delivery and applications.

    PubMed

    Ulubayram, Kezban; Calamak, Semih; Shahbazi, Reza; Eroglu, Ipek

    2015-01-01

    Infections caused by microorganisms like bacteria, fungi, etc. are the main obstacle in healing processes. Conventional antibacterial administration routes can be listed as oral, intravenous/intramuscular, topical and inhalation. These kinds of drug administrations are faced with critical vital issues such as; more rapid delivery of the drug than intended which can result in bacterial resistance, dose related systemic toxicity, tissue irritation and finally delayed healing process that need to be tackled. Recently, studies have been focused on new drug delivery systems, overcoming resistance and toxicological problems and finally localizing the molecules at the site of action in a proper dose. In this regard, many nanotechnological approaches such as nanoparticulate therapeutic systems have been developed to address accompanying problems mentioned above. Among them, drug loaded electrospun nanofibers propose main advantages like controlled drug delivery, high drug loading capacity, high encapsulation efficiency, simultaneous delivery of multiple drugs, ease of production and cost effectiveness for pharmaceutical and biomedical applications. Therefore, some particular attention has been devoted to the design of electrospun nanofibers as promising antibacterial drug carrier systems. A variety of antibacterials e.g., biocides, antibiotics, quaternary ammonium salts, triclosan, metallic nanoparticles (silver, titanium dioxide, and zinc oxide) and antibacterial polymers (chitosan, polyethyleneimine, etc.) have been impregnated by various techniques into nanofibers that exhibit strong antibacterial activity in standard assays. This review highlights the design and delivery of antibacterial drug loaded nanofibers with particular focus on their function in the fields of drug delivery, wound healing, tissue engineering, cosmetics and other biomedical applications. PMID:25732666

  20. Virtual screening and its integration with modern drug design technologies.

    PubMed

    Guido, Rafael V C; Oliva, Glaucius; Andricopulo, Adriano D

    2008-01-01

    Drug discovery is a highly complex and costly process, which demands integrated efforts in several relevant aspects involving innovation, knowledge, information, technologies, expertise, R&D investments and management skills. The shift from traditional to genomics- and proteomics-based drug research has fundamentally transformed key R&D strategies in the pharmaceutical industry addressed to the design of new chemical entities as drug candidates against a variety of biological targets. Therefore, drug discovery has moved toward more rational strategies based on our increasing understanding of the fundamental principles of protein-ligand interactions. The combination of available knowledge of several 3D protein structures with hundreds of thousands of small-molecules have attracted the attention of scientists from all over the world for the application of structure- and ligand-based drug design approaches. In this context, virtual screening technologies have largely enhanced the impact of computational methods applied to chemistry and biology and the goal of applying such methods is to reduce large compound databases and to select a limited number of promising candidates for drug design. This review provides a perspective of the utility of virtual screening in drug design and its integration with other important drug discovery technologies such as high-throughput screening (HTS) and QSAR, highlighting the present challenges, limitations, and future perspectives in medicinal chemistry.

  1. Calculator program aids sucker-rod systems design and optimization

    SciTech Connect

    Engineer, R.; Davis, C.; Knight, R.

    1983-08-01

    Given a few basic well parameters, the engineer may follow the step-by-step procedure for programming the design of sucker rod pumping systems for oil wells deeper than 2,000 ft using the HP-41 CV hand calculator.

  2. Armchair Survey Sampling: An Aid in Teaching Survey Design.

    ERIC Educational Resources Information Center

    Thompson, M. E.

    A fictitious community of 583 households was set up to simulate a survey population, and was used in two laboratory assignments where students "interviewed" householders by a quota sampling procedure and tested the performance of several probability sampling designs. (Author/JEG)

  3. An Information-Centric Framework for Designing Patient-Centered Medical Decision Aids and Risk Communication

    PubMed Central

    Franklin, Lyndsey; Plaisant, Catherine; Shneiderman, Ben

    2013-01-01

    Risk communication is a major challenge in productive patient-physician communication. Patient decision making responsibilities come with an implicit assumption that patients are sufficiently educated and confident in their abilities to make decisions about their care based on evidence based treatment recommendations. Attempts to improve health literacy in patients by way of graphical decision aids have met with success. Such decision aids typically have been designed for a general population and evaluated based on whether or not users of the decision aid can accurately report the data points in isolation. To classify decision aids, we present an information-centric framework for assessing the content delivered to patients. We provide examples of our framework from a literature survey and suggest ways improvements can be made by considering all dimensions of our framework. PMID:24551350

  4. Online Design Aid for Evaluating Manure Pit Ventilation Systems to Reduce Entry Risk.

    PubMed

    Manbeck, Harvey B; Hofstetter, Daniel W; Murphy, Dennis J; Puri, Virendra M

    2016-01-01

    On-farm manure storage pits contain both toxic and asphyxiating gases such as hydrogen sulfide, carbon dioxide, methane, and ammonia. Farmers and service personnel occasionally need to enter these pits to conduct repair and maintenance tasks. One intervention to reduce the toxic and asphyxiating gas exposure risk to farm workers when entering manure pits is manure pit ventilation. This article describes an online computational fluid dynamics-based design aid for evaluating the effectiveness of manure pit ventilation systems to reduce the concentrations of toxic and asphyxiating gases in the manure pits. This design aid, developed by a team of agricultural engineering and agricultural safety specialists at Pennsylvania State University, represents the culmination of more than a decade of research and technology development effort. The article includes a summary of the research efforts leading to the online design aid development and describes protocols for using the online design aid, including procedures for data input and for accessing design aid results. Design aid results include gas concentration decay and oxygen replenishment curves inside the manure pit and inside the barns above the manure pits, as well as animated motion pictures of individual gas concentration decay and oxygen replenishment in selected horizontal and vertical cut plots in the manure pits and barns. These results allow the user to assess (1) how long one needs to ventilate the pits to remove toxic and asphyxiating gases from the pit and barn, (2) from which portions of the barn and pit these gases are most and least readily evacuated, and (3) whether or not animals and personnel need to be removed from portions of the barn above the manure pit being ventilated.

  5. Online Design Aid for Evaluating Manure Pit Ventilation Systems to Reduce Entry Risk

    PubMed Central

    Manbeck, Harvey B.; Hofstetter, Daniel W.; Murphy, Dennis J.; Puri, Virendra M.

    2016-01-01

    On-farm manure storage pits contain both toxic and asphyxiating gases such as hydrogen sulfide, carbon dioxide, methane, and ammonia. Farmers and service personnel occasionally need to enter these pits to conduct repair and maintenance tasks. One intervention to reduce the toxic and asphyxiating gas exposure risk to farm workers when entering manure pits is manure pit ventilation. This article describes an online computational fluid dynamics-based design aid for evaluating the effectiveness of manure pit ventilation systems to reduce the concentrations of toxic and asphyxiating gases in the manure pits. This design aid, developed by a team of agricultural engineering and agricultural safety specialists at Pennsylvania State University, represents the culmination of more than a decade of research and technology development effort. The article includes a summary of the research efforts leading to the online design aid development and describes protocols for using the online design aid, including procedures for data input and for accessing design aid results. Design aid results include gas concentration decay and oxygen replenishment curves inside the manure pit and inside the barns above the manure pits, as well as animated motion pictures of individual gas concentration decay and oxygen replenishment in selected horizontal and vertical cut plots in the manure pits and barns. These results allow the user to assess (1) how long one needs to ventilate the pits to remove toxic and asphyxiating gases from the pit and barn, (2) from which portions of the barn and pit these gases are most and least readily evacuated, and (3) whether or not animals and personnel need to be removed from portions of the barn above the manure pit being ventilated. PMID:27303661

  6. Online Design Aid for Evaluating Manure Pit Ventilation Systems to Reduce Entry Risk.

    PubMed

    Manbeck, Harvey B; Hofstetter, Daniel W; Murphy, Dennis J; Puri, Virendra M

    2016-01-01

    On-farm manure storage pits contain both toxic and asphyxiating gases such as hydrogen sulfide, carbon dioxide, methane, and ammonia. Farmers and service personnel occasionally need to enter these pits to conduct repair and maintenance tasks. One intervention to reduce the toxic and asphyxiating gas exposure risk to farm workers when entering manure pits is manure pit ventilation. This article describes an online computational fluid dynamics-based design aid for evaluating the effectiveness of manure pit ventilation systems to reduce the concentrations of toxic and asphyxiating gases in the manure pits. This design aid, developed by a team of agricultural engineering and agricultural safety specialists at Pennsylvania State University, represents the culmination of more than a decade of research and technology development effort. The article includes a summary of the research efforts leading to the online design aid development and describes protocols for using the online design aid, including procedures for data input and for accessing design aid results. Design aid results include gas concentration decay and oxygen replenishment curves inside the manure pit and inside the barns above the manure pits, as well as animated motion pictures of individual gas concentration decay and oxygen replenishment in selected horizontal and vertical cut plots in the manure pits and barns. These results allow the user to assess (1) how long one needs to ventilate the pits to remove toxic and asphyxiating gases from the pit and barn, (2) from which portions of the barn and pit these gases are most and least readily evacuated, and (3) whether or not animals and personnel need to be removed from portions of the barn above the manure pit being ventilated. PMID:27303661

  7. Costs incurred by applying computer-aided design/computer-aided manufacturing techniques for the reconstruction of maxillofacial defects.

    PubMed

    Rustemeyer, Jan; Melenberg, Alex; Sari-Rieger, Aynur

    2014-12-01

    This study aims to evaluate the additional costs incurred by using a computer-aided design/computer-aided manufacturing (CAD/CAM) technique for reconstructing maxillofacial defects by analyzing typical cases. The medical charts of 11 consecutive patients who were subjected to the CAD/CAM technique were considered, and invoices from the companies providing the CAD/CAM devices were reviewed for every case. The number of devices used was significantly correlated with cost (r = 0.880; p < 0.001). Significant differences in mean costs were found between cases in which prebent reconstruction plates were used (€3346.00 ± €29.00) and cases in which they were not (€2534.22 ± €264.48; p < 0.001). Significant differences were also obtained between the costs of two, three and four devices, even when ignoring the cost of reconstruction plates. Additional fees provided by statutory health insurance covered a mean of 171.5% ± 25.6% of the cost of the CAD/CAM devices. Since the additional fees provide financial compensation, we believe that the CAD/CAM technique is suited for wide application and not restricted to complex cases. Where additional fees/funds are not available, the CAD/CAM technique might be unprofitable, so the decision whether or not to use it remains a case-to-case decision with respect to cost versus benefit.

  8. Computer-aided design of aptamers for cytochrome p450.

    PubMed

    Shcherbinin, Dmitrii S; Gnedenko, Oksana V; Khmeleva, Svetlana A; Usanov, Sergey A; Gilep, Andrei A; Yantsevich, Aliaksei V; Shkel, Tatsiana V; Yushkevich, Ivan V; Radko, Sergey P; Ivanov, Alexis S; Veselovsky, Alexander V; Archakov, Alexander I

    2015-08-01

    Aptamers are short single-stranded DNA or RNA oligonucleotides that can bind to their targets with high affinity and specificity. Usually, they are experimentally selected using the SELEX method. Here, we describe an approach toward the in silico selection of aptamers for proteins. This approach involves three steps: finding a potential binding site, designing the recognition and structural parts of the aptamers and evaluating the experimental affinity. Using this approach, a set of 15-mer aptamers for cytochrome P450 51A1 was designed using docking and molecular dynamics simulation. An experimental evaluation of the synthesized aptamers using SPR biosensor showed that these aptamers interact with cytochrome P450 51A1 with Kd values in the range of 10(-6)-10(-7) M. PMID:26166326

  9. Organic Carbamates in Drug Design and Medicinal Chemistry

    PubMed Central

    2016-01-01

    The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug–target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent applications of carbamates in drug design and medicinal chemistry. PMID:25565044

  10. Adverse Drug Reactions in HIV/AIDS Patients at a Tertiary Care Hospital in Penang, Malaysia.

    PubMed

    Khan, Kashifullah; Khan, Amer Hayat; Sulaiman, Syed Azhar; Soo, Chow Ting; Akhtar, Ali

    2016-01-01

    In the current study we explored the occurrence of adverse drug reactions (ADRs) to antiretroviral therapy among human immune-deficiency virus (HIV)/AIDS patients. We concluded an observational retrospective study in all patients who were diagnosed with HIV infection and were receiving highly active antiviral therapy from Jan. 2007 to Dec. 2012 at Hospital Pulau Pinang, Malaysia. Patient socio-demographic details along with clinical features and susceptible ADRs were observed during the study period. Out of 743 patients, 571 (76.9%) were men, and 172 (23.1%) were women. Overall 314 (42.2%) patients experienced ADRs. A total of 425 ADRs were reported, with 311 (73.1%) occurring in men and 114 (26.8%) in women, with a significant statistical relationship (P value (P) = 0.02, OR = 1.21). Overall 239 (56.2%) ADRs were recorded among Chinese, 94 (22.1%) in Malay, and 71 (16.7%) in Indian patients, which had a statistically significant association with ADRs (P = 0.05, OR = 1.50). Out of a total 425 among ADRs, lipodystrophy was recorded in 151 (35.5%) followed by skin rashes in 80 (18.8%), anemia in 74 (17.4%), and peripheral neuropathy in 27 (6.3%) patients. These findings suggest a need of intensive monitoring of ADRs in HIV treatment centres across Malaysia.

  11. Computer Aided Design of Computer Generated Holograms for electron beam fabrication

    NASA Technical Reports Server (NTRS)

    Urquhart, Kristopher S.; Lee, Sing H.; Guest, Clark C.; Feldman, Michael R.; Farhoosh, Hamid

    1989-01-01

    Computer Aided Design (CAD) systems that have been developed for electrical and mechanical design tasks are also effective tools for the process of designing Computer Generated Holograms (CGHs), particularly when these holograms are to be fabricated using electron beam lithography. CAD workstations provide efficient and convenient means of computing, storing, displaying, and preparing for fabrication many of the features that are common to CGH designs. Experience gained in the process of designing CGHs with various types of encoding methods is presented. Suggestions are made so that future workstations may further accommodate the CGH design process.

  12. The development of a spreadsheet-aided-engineering design tool for parachutes

    SciTech Connect

    Waye, D.E.; Whinery, L.D.

    1997-04-01

    A spreadsheet-aided engineering design tool has been developed to assist in the parachute design process. The new tool was developed during FY96 and utilized in the design of the flight termination parachute system for a 1900 lb. payload. Many modifications were made during the initial utilization of this tool. Work on the tool continues as the authors attempt to create an application tool for the parachute engineer.

  13. Computer-aided design of millimeter-wave E-plane filters

    NASA Astrophysics Data System (ADS)

    Shih, Y.-C.; Itoh, T.; Bui, L. Q.

    1983-02-01

    A computer-aided design (CAD) algorithm has been developed for a class of E-plane bandpass filters. The analysis portion of the algorithm is based on the residue-calculus technique and a generalized scattering parameter method. It is mathematically exact and numerically very efficient. Filters designed with this method have been fabricated and tested in Ka-band. Good agreement with design has been obtained.

  14. A methodology and a tool for the computer aided design with constraints of electrical devices

    SciTech Connect

    Wurtz, F.; Bigeon, J.; Poirson, C.

    1996-05-01

    A methodology for the computer aided constrained design of electrical devices is presented and validated through the design of a slotless permanent structure. It is based on the use of the analytical design equations of the device. Symbolic calculation is widely used to generate an analysis program and a sensitivity computation program. Those programs are linked with an optimization algorithm that can take constraints into account. The methodology is tested with an experimental software named PASCOSMA.

  15. Reliance by gay men and intravenous drug users on friends and family for AIDS-related care.

    PubMed

    Johnston, D; Stall, R; Smith, K

    1995-01-01

    A group of gay-identified men (n = 81) and intravenous drug users (n = 88) diagnosed with AIDS in San Francisco were interviewed regarding their use of friends and family to meet their care needs. Analytic of quantitative data revealed that gay men relied more than did IDUs on friends for care. Neither group relied primarily on their families for care. Analysis of the qualitative data identified five primary barriers to care. First, many people with AIDS are not accustomed to asking for help and often avoid it when possible. Second, the social stigma surrounding AIDS sometimes leads to isolation. Third, some people with AIDS have kin with health problems of their own, thereby sometimes compromising this potential source of care. Fourth, the AIDS epidemic has devastated identifiable sub-populations, leaving surviving members of these groups emotionally exhausted and sometimes unable to provide as much help as they might have liked. Finally, some respondents choose to voluntarily cut themselves off from 'supportive' relationships that they perceive to be destructive now that they have been diagnosed with a fatal illness. Professional care providers and health care planners should be aware of dynamics within informal care networks of people with AIDS that may leave patients without necessary care.

  16. Methods to Design and Synthesize Antibody-Drug Conjugates (ADCs)

    PubMed Central

    Yao, Houzong; Jiang, Feng; Lu, Aiping; Zhang, Ge

    2016-01-01

    Antibody-drug conjugates (ADCs) have become a promising targeted therapy strategy that combines the specificity, favorable pharmacokinetics and biodistributions of antibodies with the destructive potential of highly potent drugs. One of the biggest challenges in the development of ADCs is the application of suitable linkers for conjugating drugs to antibodies. Recently, the design and synthesis of linkers are making great progress. In this review, we present the methods that are currently used to synthesize antibody-drug conjugates by using thiols, amines, alcohols, aldehydes and azides. PMID:26848651

  17. Exploiting personalized information for reagent selection in drug design.

    PubMed

    Boström, Jonas; Falk, Niklas; Tyrchan, Christian

    2011-03-01

    Drug discovery is currently being industrialized. This fact is confusing, given that it is happening in times when the rest of the world has entered the subsequent information age. Here, we introduce a concept and an infrastructure for the now popular and well-known recommender systems in the context of exploiting one of the cornerstones of drug design: chemical reagent selection. The goal is to create and transfer information openly to facilitate intuition and serendipity in drug design. The system is tailored to highlight reagents from our corporate reagent database; reagents that a chemist might not have considered based purely on their own experience.

  18. CNS drug design: balancing physicochemical properties for optimal brain exposure.

    PubMed

    Rankovic, Zoran

    2015-03-26

    The human brain is a uniquely complex organ, which has evolved a sophisticated protection system to prevent injury from external insults and toxins. Designing molecules that can overcome this protection system and achieve optimal concentration at the desired therapeutic target in the brain is a specific and major challenge for medicinal chemists working in CNS drug discovery. Analogous to the now widely accepted rule of 5 in the design of oral drugs, the physicochemical properties required for optimal brain exposure have been extensively studied in an attempt to similarly define the attributes of successful CNS drugs and drug candidates. This body of work is systematically reviewed here, with a particular emphasis on the interplay between the most critical physicochemical and pharmacokinetic parameters of CNS drugs as well as their impact on medicinal chemistry strategies toward molecules with optimal brain exposure. A summary of modern CNS pharmacokinetic concepts and methods is also provided.

  19. Micrometric precision of prosthetic dental crowns obtained by optical scanning and computer-aided designing/computer-aided manufacturing system

    NASA Astrophysics Data System (ADS)

    das Neves, Flávio Domingues; de Almeida Prado Naves Carneiro, Thiago; do Prado, Célio Jesus; Prudente, Marcel Santana; Zancopé, Karla; Davi, Letícia Resende; Mendonça, Gustavo; Soares, Carlos José

    2014-08-01

    The current study evaluated prosthetic dental crowns obtained by optical scanning and a computer-aided designing/computer-aided manufacturing system using micro-computed tomography to compare the marginal fit. The virtual models were obtained with four different scanning surfaces: typodont (T), regular impressions (RI), master casts (MC), and powdered master casts (PMC). Five virtual models were obtained for each group. For each model, a crown was designed on the software and milled from feldspathic ceramic blocks. Micro-CT images were obtained for marginal gap measurements and the data were statistically analyzed by one-way analysis of variance followed by Tukey's test. The mean vertical misfit was T=62.6±65.2 μm; MC=60.4±38.4 μm; PMC=58.1±38.0 μm, and RI=89.8±62.8 μm. Considering a percentage of vertical marginal gap of up to 75 μm, the results were T=71.5%, RI=49.2%, MC=69.6%, and PMC=71.2%. The percentages of horizontal overextension were T=8.5%, RI=0%, MC=0.8%, and PMC=3.8%. Based on the results, virtual model acquisition by scanning the typodont (simulated mouth) or MC, with or without powder, showed acceptable values for the marginal gap. The higher result of marginal gap of the RI group suggests that it is preferable to scan this directly from the mouth or from MC.

  20. Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design.

    PubMed

    Bauman, Joseph D; Das, Kalyan; Ho, William C; Baweja, Mukta; Himmel, Daniel M; Clark, Arthur D; Oren, Deena A; Boyer, Paul L; Hughes, Stephen H; Shatkin, Aaron J; Arnold, Eddy

    2008-09-01

    HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at approximately 2.5-3.0 A resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of attempts, it was not possible to obtain the structure of a complex of HIV-1 RT with TMC278, a nonnucleoside RT inhibitor (NNRTI) in advanced clinical trials. A systematic and iterative protein crystal engineering approach was developed to optimize RT for obtaining crystals in complexes with TMC278 and other NNRTIs that diffract X-rays to 1.8 A resolution. Another form of engineered RT was optimized to produce a high-resolution apo-RT crystal form, reported here at 1.85 A resolution, with a distinct RT conformation. Engineered RTs were mutagenized using a new, flexible and cost effective method called methylated overlap-extension ligation independent cloning. Our analysis suggests that reducing the solvent content, increasing lattice contacts, and stabilizing the internal low-energy conformations of RT are critical for the growth of crystals that diffract to high resolution. The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs.

  1. Crystal Engineering of HIV-1 Reverse Transcriptase for structure-Based Drug Design

    SciTech Connect

    Bauman,J.; Das, K.; Ho, W.; Baweja, M.; Himmel, D.; Clark, A.; Oren, D.; Shatkin, A.; Arnold, E.

    2008-01-01

    HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at {approx}2.5-3.0 Angstroms resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of attempts, it was not possible to obtain the structure of a complex of HIV-1 RT with TMC278, a nonnucleoside RT inhibitor (NNRTI) in advanced clinical trials. A systematic and iterative protein crystal engineering approach was developed to optimize RT for obtaining crystals in complexes with TMC278 and other NNRTIs that diffract X-rays to 1.8 Angstroms resolution. Another form of engineered RT was optimized to produce a high-resolution apo-RT crystal form, reported here at 1.85 Angstroms resolution, with a distinct RT conformation. Engineered RTs were mutagenized using a new, flexible and cost effective method called methylated overlap-extension ligation independent cloning. Our analysis suggests that reducing the solvent content, increasing lattice contacts, and stabilizing the internal low-energy conformations of RT are critical for the growth of crystals that diffract to high resolution. The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs.

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

    NASA Astrophysics Data System (ADS)

    Lueshen, Eric

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

  3. Computer program for design and performance analysis of navigation-aid power systems

    NASA Technical Reports Server (NTRS)

    Weiner, H.; Wiener, P.; Williams, K.

    1976-01-01

    The paper examines the requirements, design rationale, operation, and verification of a computer program designated as design synthesis/performance analysis (DSPA) computer program, which is capable of performing all the calculations necessary to understand the overall characteristics of solar array/battery power systems for navigation-aid applications. Despite the uncertainties in the erratic solar array degradation data and the potential impact on actual battery behavior, verification of the DSPA is considered successful. The program is shown to have the capability of simulating the performance of solar array/battery navigation-aid power systems. It can also be used to synthesize power system designs and provide essential design and cost data.

  4. 21 CFR 316.27 - Change in ownership of orphan-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Change in ownership of orphan-drug designation... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.27 Change in ownership of orphan-drug designation. (a) A sponsor may transfer ownership of or any beneficial interest...

  5. Design strategies for computational fragment-based drug design.

    PubMed

    Konteatis, Zenon D

    2015-01-01

    The computational design method described in this chapter is an approach to de-risking the design process due to the limitations of current computational algorithms with respect to predictive accuracy. The method takes advantage of the crystallographically demonstrated interactions between a ligand and its protein target, and through systematic, one fragment replacements allows for quick feedback on the direction of the designs. This design approach can still be useful in the future as computational algorithms improve and become more predictive and reliable.

  6. DeMAID/GA an Enhanced Design Manager's Aid for Intelligent Decomposition

    NASA Technical Reports Server (NTRS)

    Rogers, J. L.

    1996-01-01

    Many companies are looking for new tools and techniques to aid a design manager in making decisions that can reduce the time and cost of a design cycle. One tool is the Design Manager's Aid for Intelligent Decomposition (DeMAID). Since the initial public release of DeMAID in 1989, much research has been done in the areas of decomposition, concurrent engineering, parallel processing, and process management; many new tools and techniques have emerged. Based on these recent research and development efforts, numerous enhancements have been added to DeMAID to further aid the design manager in saving both cost and time in a design cycle. The key enhancement, a genetic algorithm (GA), will be available in the next public release called DeMAID/GA. The GA sequences the design processes to minimize the cost and time in converging a solution. The major enhancements in the upgrade of DeMAID to DeMAID/GA are discussed in this paper. A sample conceptual design project is used to show how these enhancements can be applied to improve the design cycle.

  7. Assembly and insertion of a self-fitting hearing aid: design of effective instruction materials.

    PubMed

    Caposecco, Andrea; Hickson, Louise; Meyer, Carly

    2011-12-01

    A self-fitting hearing aid has been proposed as a viable option to meet the need for rehabilitation in areas where audiology services are unreliable. A successful outcome with a self-fitting hearing aid pivots in part on the clarity of the instructions accompanying the device. The aims of this article are (a) to review the literature to determine features that should be incorporated into written health-care materials and factors to consider in the design process when developing written instructions for a target audience of older adults and (b) to apply this information to the development of a set of written instructions as the first step in self-fitting of a hearing aid, assembling four parts and inserting the aid into the ear. The method involved a literature review of published peer reviewed research. The literature revealed four steps in the development of written health-care materials: planning, design, assessment of suitability, and pilot testing. Best practice design principles for each step were applied in the development of instructions for how to assemble and insert a hearing aid. Separate booklets were developed for the left and right aids and the content of each consisted of simple line drawings accompanied by captions. The reading level was Grade 3.5 equivalent and the Flesch Reading Ease Score was 91.1 indicating that the materials were "very easy" to read. It is essential to follow best practice design principles when developing written health-care materials to motivate the reader, maximize comprehension, and increase the likelihood of successful application of the content.

  8. Assembly and insertion of a self-fitting hearing aid: design of effective instruction materials.

    PubMed

    Caposecco, Andrea; Hickson, Louise; Meyer, Carly

    2011-12-01

    A self-fitting hearing aid has been proposed as a viable option to meet the need for rehabilitation in areas where audiology services are unreliable. A successful outcome with a self-fitting hearing aid pivots in part on the clarity of the instructions accompanying the device. The aims of this article are (a) to review the literature to determine features that should be incorporated into written health-care materials and factors to consider in the design process when developing written instructions for a target audience of older adults and (b) to apply this information to the development of a set of written instructions as the first step in self-fitting of a hearing aid, assembling four parts and inserting the aid into the ear. The method involved a literature review of published peer reviewed research. The literature revealed four steps in the development of written health-care materials: planning, design, assessment of suitability, and pilot testing. Best practice design principles for each step were applied in the development of instructions for how to assemble and insert a hearing aid. Separate booklets were developed for the left and right aids and the content of each consisted of simple line drawings accompanied by captions. The reading level was Grade 3.5 equivalent and the Flesch Reading Ease Score was 91.1 indicating that the materials were "very easy" to read. It is essential to follow best practice design principles when developing written health-care materials to motivate the reader, maximize comprehension, and increase the likelihood of successful application of the content. PMID:22389434

  9. Design of a Multiple Drug Delivery System Directed at Periodontitis

    PubMed Central

    Sundararaj, Sharath C.; Thomas, Mark V.; Peyyala, Rebecca; Dziubla, Thomas D.; Puleo, David A.

    2013-01-01

    Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions. PMID:23948165

  10. High-throughput crystallography for lead discovery in drug design.

    PubMed

    Blundell, Tom L; Jhoti, Harren; Abell, Chris

    2002-01-01

    Knowledge of the three-dimensional structures of protein targets now emerging from genomic data has the potential to accelerate drug discovery greatly. X-ray crystallography is the most widely used technique for protein structure determination, but technical challenges and time constraints have traditionally limited its use primarily to lead optimization. Here, we describe how significant advances in process automation and informatics have aided the development of high-throughput X-ray crystallography, and discuss the use of this technique for structure-based lead discovery.

  11. Design of an aid to visual inspection workstation

    NASA Astrophysics Data System (ADS)

    Tait, Robert; Harding, Kevin

    2016-05-01

    Visual Inspection is the most common means for inspecting manufactured parts for random defects such as pits, scratches, breaks, corrosion or general wear. The reason for the need for visual inspection is the very random nature of what might be a defect. Some defects may be very rare, being seen once or twice a year, but May still be critical to part performance. Because of this random and rare nature, even the most sophisticated image analysis programs have not been able to recognize all possible defects. Key to any future automation of inspection is obtaining good sample images of what might be a defect. However, most visual check take no images and consequently generate no digital data or historical record beyond a simple count. Any additional tool to captures such images must be able to do so without taking addition time. This paper outlines the design of a potential visual inspection station that would be compatible with current visual inspection methods, but afford the means for reliable digital imaging and in many cases augmented capabilities to assist the inspection. Considerations in this study included: resolution, depth of field, feature highlighting, and ease of digital capture, annotations and inspection augmentation for repeatable registration as well as operator assistance and training.

  12. Evolution of Antiretroviral Drug Costs in Brazil in the Context of Free and Universal Access to AIDS Treatment

    PubMed Central

    Nunn, Amy S; Fonseca, Elize M; Bastos, Francisco I; Gruskin, Sofia; Salomon, Joshua A

    2007-01-01

    Background Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005. Methods and Findings We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir–ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six

  13. Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review

    PubMed Central

    Oliveira, Natalia Mejias; Ferreira, Felipe Augusto Yamauti; Yonamine, Raquel Yumi; Chehter, Ethel Zimberg

    2014-01-01

    ABSTRACT In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug

  14. Simulation tools for computer-aided design and numerical investigations of high-power gyrotrons

    NASA Astrophysics Data System (ADS)

    Damyanova, M.; Balabanova, E.; Kern, S.; Illy, S.; Sabchevski, S.; Thumm, M.; Vasileva, E.; Zhelyazkov, I.

    2012-03-01

    Modelling and simulation are essential tools for computer-aided design (CAD), analysis and optimization of high-power gyrotrons used as radiation sources for electron cyclotron resonance heating (ECRH) and current drive (ECCD) of magnetically confined plasmas in the thermonuclear reactor ITER. In this communication, we present the current status of our simulation tools and discuss their further development.

  15. The state of PC-based CADD (computer-aided design and drafting) systems

    SciTech Connect

    Brandt, G.L.; Bowers, J.M.; Gorman, T.S.; Taylor, L.E.

    1988-07-11

    This report provides an overview of the state of the art of personal computer (PC)-based computer-aided design and drafting (CADD) systems for mechanical engineering applications. It presents the results of an evaluation performed on seven systems during October 1987 to March 1988 and summarizes the strengths and weaknesses of the systems.

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

    ERIC Educational Resources Information Center

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

    2002-01-01

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

  17. New Spaces for Learning: Designing College Facilities to Utilize Instructional Aids and Media. Revised.

    ERIC Educational Resources Information Center

    Hauf, Harold D.; And Others

    Colleges need appropriate large group instructional facilities for effective and efficient use of instructional aids and media. A well planned system of facilities must provide space for learning; production, origination, and support; storage and retrieval. Design begins with a building plan--a statement, made jointly by the administrator and…

  18. The Design, Implementation, and Formative Evaluation of a Classroom Aide Professional Development Training Program

    ERIC Educational Resources Information Center

    Dulfer, Katherine J.

    2013-01-01

    This dissertation focused on the process of designing, implementing, and formatively evaluating an eight week Classroom Aide Professional Development Training Program (CAPD-TP) on behavior management and academic instruction within the context of a New Jersey state approved private special education school for students with behavioral and/or…

  19. Therapist-Aided Exposure for Women with Lifelong Vaginismus: A Replicated Single-Case Design

    ERIC Educational Resources Information Center

    ter Kuile, Moniek M.; Bulte, Isis; Weijenborg, Philomeen T. M.; Beekman, Aart; Melles, Reinhilde; Onghena, Patrick

    2009-01-01

    Vaginismus is commonly described as a persistent difficulty in allowing vaginal entry of a penis or other object. Lifelong vaginismus occurs when a woman has never been able to have intercourse. A replicated single-case A-B-phase design was used to investigate the effectiveness of therapist-aided exposure for lifelong vaginismus. A baseline period…

  20. National Science Foundation 1989 Engineering Senior Design Projects To Aid the Disabled.

    ERIC Educational Resources Information Center

    Enderle, John D., Ed.

    Through the Bioengineering and Research to Aid the Disabled program of the National Science Foundation, design projects were awarded competitively to 16 universities. Senior engineering students at each of the universities constructed custom devices and software for disabled individuals. This compendium contains a description of each project in…

  1. Gathering Empirical Evidence Concerning Links between Computer Aided Design (CAD) and Creativity

    ERIC Educational Resources Information Center

    Musta'amal, Aede Hatib; Norman, Eddie; Hodgson, Tony

    2009-01-01

    Discussion is often reported concerning potential links between computer-aided designing and creativity, but there is a lack of systematic enquiry to gather empirical evidence concerning such links. This paper reports an indication of findings from other research studies carried out in contexts beyond general education that have sought evidence…

  2. Office of Student Financial Aid Quality Improvement Program: Design and Implementation Plan.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    The purpose and direction of the Office of Student Financial Aid (OSFA) quality improvement program are described. The background and context for the Pell Grant quality control (QC) design study and the meaning of QC are reviewed. The general approach to quality improvement consists of the following elements: a strategic approach that enables OSFA…

  3. A drug-specific nanocarrier design for efficient anticancer therapy

    NASA Astrophysics Data System (ADS)

    Shi, Changying; Guo, Dandan; Xiao, Kai; Wang, Xu; Wang, Lili; Luo, Juntao

    2015-07-01

    The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here we customize telodendrimers (linear dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug-binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumour targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.

  4. A drug-specific nanocarrier design for efficient anticancer therapy

    PubMed Central

    Shi, Changying; Guo, Dandan; Xiao, Kai; Wang, Xu; Wang, Lili; Luo, Juntao

    2015-01-01

    The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here, we customize telodendrimers (linear-dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumor targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery. PMID:26158623

  5. Low-floor bus design preferences of walking aid users during simulated boarding and alighting.

    PubMed

    D'souza, Clive; Paquet, Victor; Lenker, James; Steinfeld, Edward; Bareria, Piyush

    2012-01-01

    Low-floor buses represent a significant improvement in accessible public transit for passengers with limited mobility. However, there is still a need for research on the inclusive design of transit buses to identify specific low-floor bus design conditions that are either particularly accommodating or challenging for passengers with functional and mobility impairments. These include doorway locations, seating configuration and the large front wheel-well covers that collectively impact boarding, alighting and interior movement of passengers. Findings from a laboratory study using a static full-scale simulation of a lowfloor bus to evaluate the impact of seating configuration and crowding on interior movement and accessibility for individuals with and without walking aids are presented (n=41). Simulated bus journeys that included boarding, fare payment, seating, and alighting were performed. Results from video observations and subjective assessments showed differences in boarding and alighting performance and users' perceptions of task difficulty. The need for assistive design features (e.g. handholds, stanchions), legroom and stowage space for walking aids was evident. These results demonstrate that specific design conditions in low-floor buses can significantly impact design preference among those who use walking aids. Consideration of ergonomics and inclusive design can therefore be used to improve the design of low-floor buses.

  6. Computer-aided design of a proton pump

    NASA Technical Reports Server (NTRS)

    New, Michael H.; Pohorille, Andrew; Chang, Sherwood (Technical Monitor)

    1997-01-01

    The use of transmembrane proton gradients in energy transduction is an almost universal feature of life on earth. These proton gradients are established and maintained by specialized assemblies of proteins which actively pump protons across membranes. One broad class of proton pumps uses captured light energy to drive the proton pumping. Our goal is to elucidate the minimum structural requirements of a light-driven proton-pump. There are two basic components to a simple light-driven proton pump: a source of photo-generated protons and a "gate-keeper" which prevents these protons from reattaching themselves to their source. A wide variety of molecules in the membrane, even as simple as polycyclic aromatic hydrocarbons, are capable of releasing protons when illuminated. Our work is therefore focused on the design of the "gate-keeper." Our initial model involves a pair of proton acceptors, coupled to each other by a transient water bridge, and supported in the membrane by a small bundle of peptide helices. Upon illumination, the proton source transfers its proton to the:- first acceptor of the gate-keeper. While the reverse reaction is highly probable, all that is needed to ensure irreversibility is a nonvanishing probability that the proton will be transferred to the second acceptor across a transient water bridge. Back transfer of the proton to the first acceptor, and thence to the proton source, is impeded by the free energy required to move the proton uphill towards the. proton source and by the disruption of the transient water bridge. As a prototypical water-bridged proton transfer system, we are studying the transfer of a proton across a water bridge from a formic acid to a formate anion. With a pK(sub alpha), of 3.7. formic acid is a good model for the acidic amino acids glutamate and aspartate which are good candidates for gate-keeper proton acceptors. Simulations of proton transfer reactions in a membrane are complicated by the quantum mechanical nature of

  7. De Novo Fragment Design for Drug Discovery and Chemical Biology.

    PubMed

    Rodrigues, Tiago; Reker, Daniel; Welin, Martin; Caldera, Michael; Brunner, Cyrill; Gabernet, Gisela; Schneider, Petra; Walse, Björn; Schneider, Gisbert

    2015-12-01

    Automated molecular de novo design led to the discovery of an innovative inhibitor of death-associated protein kinase 3 (DAPK3). An unprecedented crystal structure of the inactive DAPK3 homodimer shows the fragment-like hit bound to the ATP pocket. Target prediction software based on machine learning models correctly identified additional macromolecular targets of the computationally designed compound and the structurally related marketed drug azosemide. The study validates computational de novo design as a prime method for generating chemical probes and starting points for drug discovery.

  8. Low-cost generic drugs under the President's Emergency Plan for AIDS Relief drove down treatment cost; more are needed.

    PubMed

    Venkatesh, Kartik K; Mayer, Kenneth H; Carpenter, Charles C J

    2012-07-01

    The President's Emergency Plan for AIDS Relief (PEPFAR) was originally authorized in 2003 with the goal of supporting HIV prevention, treatment, and care within fifteen focus countries in the developing world. By September 2011 nearly 13 million people around the world were receiving HIV/AIDS-related care through PEPFAR, and 3.9 million were receiving antiretroviral treatment. However, in the early years of the program, access to antiretroviral drugs was hampered by the lack of a licensing process that the US government recognized for generic versions of these medications. Ultimately, the obstacle to approval of generic antiretroviral drugs was removed, which led to PEPFAR's considerable success at making these treatments widely available. This article outlines PEPFAR's evolving use of generic antiretroviral drugs to treat HIV in the developing world, highlights ongoing initiatives to increase access to generic antiretrovirals, and points to the need for mechanisms that will speed up the approval of new generic drugs. The striking decline in antiretroviral treatment costs, from $1,100 per person annually in 2004 to $335 per person annually in 2012, is due to the availability of effective generic antiretrovirals. Given growing resistance to existing drugs and the planned expansion of treatment to millions more people, access to newer generations of generic antiretrovirals will have to be expedited.

  9. Evidence-based guideline: Antiepileptic drug selection for people with HIV/AIDS

    PubMed Central

    Birbeck, G.L.; French, J.A.; Perucca, E.; Simpson, D.M.; Fraimow, H.; George, J.M.; Okulicz, J.F.; Clifford, D.B.; Hachad, H.; Levy, R.H.

    2012-01-01

    Objective: To develop guidelines for selection of antiepileptic drugs (AEDs) among people with HIV/AIDS. Methods: The literature was systematically reviewed to assess the global burden of relevant comorbid entities, to determine the number of patients who potentially utilize AEDs and antiretroviral agents (ARVs), and to address AED-ARV interactions. Results and Recommendations: AED-ARV administration may be indicated in up to 55% of people taking ARVs. Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of ∼50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C). Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of ∼50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadministration of raltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolam dosage adjustment (Level C). Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme-inducing AEDs in people on ARV regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors, as pharmacokinetic interactions may result in virologic failure, which has clinical implications for disease progression and development of ARV resistance. If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C). PMID:22218281

  10. Enveloped viruses understood via multiscale simulation: computer-aided vaccine design

    NASA Astrophysics Data System (ADS)

    Shreif, Z.; Adhangale, P.; Cheluvaraja, S.; Perera, R.; Kuhn, R.; Ortoleva, P.

    Enveloped viruses are viewed as an opportunity to understand how highly organized and functional biosystems can emerge from a collection of millions of chaotically moving atoms. They are an intermediate level of complexity between macromolecules and bacteria. They are a natural system for testing theories of self-assembly and structural transitions, and for demonstrating the derivation of principles of microbiology from laws of molecular physics. As some constitute threats to human health, a computer-aided vaccine and drug design strategy that would follow from a quantitative model would be an important contribution. However, current molecular dynamics simulation approaches are not practical for modeling such systems. Our multiscale approach simultaneously accounts for the outer protein net and inner protein/genomic core, and their less structured membranous material and host fluid. It follows from a rigorous multiscale deductive analysis of laws of molecular physics. Two types of order parameters are introduced: (1) those for structures wherein constituent molecules retain long-lived connectivity (they specify the nanoscale structure as a deformation from a reference configuration) and (2) those for which there is no connectivity but organization is maintained on the average (they are field variables such as mass density or measures of preferred orientation). Rigorous multiscale techniques are used to derive equations for the order parameters dynamics. The equations account for thermal-average forces, diffusion coefficients, and effects of random forces. Statistical properties of the atomic-scale fluctuations and the order parameters are co-evolved. By combining rigorous multiscale techniques and modern supercomputing, systems of extreme complexity can be modeled.

  11. Enveloped viruses understood via multiscale simulation: computer-aided vaccine design

    NASA Astrophysics Data System (ADS)

    Shreif, Z.; Adhangale, P.; Cheluvaraja, S.; Perera, R.; Kuhn, R.; Ortoleva, P.

    2008-04-01

    Enveloped viruses are viewed as an opportunity to understand how highly organized and functional biosystems can emerge from a collection of millions of chaotically moving atoms. They are an intermediate level of complexity between macromolecules and bacteria. They are a natural system for testing theories of self-assembly and structural transitions, and for demonstrating the derivation of principles of microbiology from laws of molecular physics. As some constitute threats to human health, a computer-aided vaccine and drug design strategy that would follow from a quantitative model would be an important contribution. However, current molecular dynamics simulation approaches are not practical for modeling such systems. Our multiscale approach simultaneously accounts for the outer protein net and inner protein/genomic core, and their less structured membranous material and host fluid. It follows from a rigorous multiscale deductive analysis of laws of molecular physics. Two types of order parameters are introduced: (1) those for structures wherein constituent molecules retain long-lived connectivity (they specify the nanoscale structure as a deformation from a reference configuration) and (2) those for which there is no connectivity but organization is maintained on the average (they are field variables such as mass density or measures of preferred orientation). Rigorous multiscale techniques are used to derive equations for the order parameters dynamics. The equations account for thermal-average forces, diffusion coefficients, and effects of random forces. Statistical properties of the atomic-scale fluctuations and the order parameters are co-evolved. By combining rigorous multiscale techniques and modern supercomputing, systems of extreme complexity can be modeled.

  12. Drug use, AIDS knowledge, and HIV risk behaviors of Cuban-, Mexican-, and Puerto-Rican-born drug injectors who are recent entrants into the United States.

    PubMed

    Freeman, R C; Williams, M L; Saunders, L A

    1999-11-01

    To date, relatively little research attention has been devoted to the HIV-risky behaviors of persons who are newly arrived in the United States and who use drugs. Data gathered from street-recruited injection drug users (IDUs) recruited in 10 United States cities who were born in Mexico, Cuba, and Puerto Rico and who are recent entrants into the United States suggest that, in comparison to US-born IDUs, Mexican-born subjects are at elevated risk for acquiring and transmitting HIV as a result of sharing needles with friends and running partners; sharing drug injection implements such as cookers, cotton, and rinse water; frequent injection in HIV-risky settings; use of unsterilized needles; and relatively frequent trading of sex for drugs or money. Puerto-Rican-born IDUs were found to inject drugs relatively frequently, and to do so relatively often in high-risk settings in which sterile injecting equipment and cleaning materials often are scarce. These data also show generally lower levels of AIDS knowledge among the in-migrant IDUs than among US-born IDUs. Respondents from each nationality group most often cited television as the source of their most useful and reliable AIDS information, but also tended to regard community outreach workers as a significant source of reliable AIDS and needle cleaning information. The high levels of involvement in HIV-risky behaviors, deficits in knowledge concerning the means of HIV transmission, and relative ease of mobility of the at-risk (for HIV) individuals examined here indicate a need for a comprehensive public health prevention initiative to limit the future spread of HIV. At a minimum, such an undertaking would do well to incorporate group-specific, culturally appropriate behavioral interventions as well as an information campaign.

  13. Advancing lighting and daylighting simulation: The transition from analysis to design aid tools

    SciTech Connect

    Hitchcock, R.J.

    1995-05-01

    This paper explores three significant software development requirements for making the transition from stand-alone lighting simulation/analysis tools to simulation-based design aid tools. These requirements include specialized lighting simulation engines, facilitated methods for creating detailed simulatable building descriptions, an automated techniques for providing lighting design guidance. Initial computer implementations meant to address each of these requirements are discussed to further elaborate these requirements and to illustrate work-in-progress.

  14. Peptides and Peptidomimetics for Antimicrobial Drug Design

    PubMed Central

    Mojsoska, Biljana; Jenssen, Håvard

    2015-01-01

    The purpose of this paper is to introduce and highlight a few classes of traditional antimicrobial peptides with a focus on structure-activity relationship studies. After first dissecting the important physiochemical properties that influence the antimicrobial and toxic properties of antimicrobial peptides, the contributions of individual amino acids with respect to the peptides antibacterial properties are presented. A brief discussion of the mechanisms of action of different antimicrobials as well as the development of bacterial resistance towards antimicrobial peptides follows. Finally, current efforts on novel design strategies and peptidomimetics are introduced to illustrate the importance of antimicrobial peptide research in the development of future antibiotics. PMID:26184232

  15. Multicriteria aided design of integrated heating-cooling energy systems in buildings.

    PubMed

    Mróz, Tomasz M

    2010-08-01

    This paper presents an analysis of the possible application of integrated heating-cooling systems in buildings. The general algorithm of integrated heating-cooling system design aid was formulated. The evaluation criteria of technically acceptable variants were defined. Fossil fuel energy consumption, carbon dioxide emission, investment, and total exploitation cost were identified as the most important factors describing the considered decision problem. The multicriteria decision aid method ELECTRE III was proposed as the decision tool for the choice of the most compromised variant. The proposed method was used for a case study calculation-the choice of an integrated heating-cooling system for an office building.

  16. The theory, design, and operation of the suppressed carrier data-aided tracking receiver

    NASA Technical Reports Server (NTRS)

    Simon, M. K.; Springett, J. C.

    1973-01-01

    A viable, efficient, and easily mechanized carrier regenerating receiver for use in suppressed carrier-tracking system is described. The receiver referred to as a data-aided receiver (DAR) incorporates a data-aided loop (DAL) which provides the required carrier reference signal. The DAL employs the principle of decision feedback and as such is more efficient than other forms of suppressed carrier-tracking loops. The analysis, design, and implementation of the DAR are covered in detail. Performance comparisons and mechanization tradeoffs are made, wherever possible, with discrete carrier systems and other suppressed carrier systems presently in use. Experimental performance verification is given throughout in support of the theory presented.

  17. Fragment-based QSAR: perspectives in drug design.

    PubMed

    Salum, Lívia B; Andricopulo, Adriano D

    2009-08-01

    Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. Quantitative structure-activity relationship (QSAR) methods are among the most important strategies that can be applied for the successful design of small molecule modulators having clinical utility. Hologram QSAR (HQSAR) is a modern 2D fragment-based QSAR method that employs specialized molecular fingerprints. HQSAR can be applied to large data sets of compounds, as well as traditional-size sets, being a versatile tool in drug design. The HQSAR approach has evolved from a classical use in the generation of standard QSAR models for data correlation and prediction into advanced drug design tools for virtual screening and pharmacokinetic property prediction. This paper provides a brief perspective on the evolution and current status of HQSAR, highlighting present challenges and new opportunities in drug design.

  18. Design and implementation of an electronic investigational drug accountability system.

    PubMed

    Grilley, B J; Trissel, L A; Bluml, B M

    1991-12-01

    A software system designed to maintain protocol-specific investigational drug accountability records is described. The University of Texas M. D. Anderson Cancer Center and Cygnus Systems Development, Inc., worked together to create an electronic investigational drug accountability system (IDRx), which meets the requirements of the National Cancer Institute. This system performs record keeping, stores information on drugs and protocols, and generates standard and customized reports. On-screen assistance makes it easy to use. Security is achieved by granting access only to authorized users, and an audit trail is automatically generated. Systematic implementation at M. D. Anderson, initially in the investigational drug control area and subsequently in the satellite pharmacies, has resulted in increased accuracy and efficiency, and few problems have been encountered. The IDRx software package is useful for keeping records, generating reports, and tracking and evaluating data associated with an investigational drug accountability system. PMID:1814202

  19. Design of Nanoparticle-Based Carriers for Targeted Drug Delivery

    PubMed Central

    Ren, Muqing; Duval, Kayla; Guo, Xing; Chen, Zi

    2016-01-01

    Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this article, we provide an overview of three different targeted drug delivery methods (passive targeting, active targeting and physical targeting), compare methods of action, advantages, limitations, and the current stage of research. For the most commonly used nanoparticle carriers, fabrication methods are also reviewed. This is followed by a review of computational simulations and models on nanoparticle-based drug delivery. PMID:27398083

  20. Mapping chemical structure-activity information of HAART-drug cocktails over complex networks of AIDS epidemiology and socioeconomic data of U.S. counties.

    PubMed

    Herrera-Ibatá, Diana María; Pazos, Alejandro; Orbegozo-Medina, Ricardo Alfredo; Romero-Durán, Francisco Javier; González-Díaz, Humberto

    2015-06-01

    Using computational algorithms to design tailored drug cocktails for highly active antiretroviral therapy (HAART) on specific populations is a goal of major importance for both pharmaceutical industry and public health policy institutions. New combinations of compounds need to be predicted in order to design HAART cocktails. On the one hand, there are the biomolecular factors related to the drugs in the cocktail (experimental measure, chemical structure, drug target, assay organisms, etc.); on the other hand, there are the socioeconomic factors of the specific population (income inequalities, employment levels, fiscal pressure, education, migration, population structure, etc.) to study the relationship between the socioeconomic status and the disease. In this context, machine learning algorithms, able to seek models for problems with multi-source data, have to be used. In this work, the first artificial neural network (ANN) model is proposed for the prediction of HAART cocktails, to halt AIDS on epidemic networks of U.S. counties using information indices that codify both biomolecular and several socioeconomic factors. The data was obtained from at least three major sources. The first dataset included assays of anti-HIV chemical compounds released to ChEMBL. The second dataset is the AIDSVu database of Emory University. AIDSVu compiled AIDS prevalence for >2300 U.S. counties. The third data set included socioeconomic data from the U.S. Census Bureau. Three scales or levels were employed to group the counties according to the location or population structure codes: state, rural urban continuum code (RUCC) and urban influence code (UIC). An analysis of >130,000 pairs (network links) was performed, corresponding to AIDS prevalence in 2310 counties in U.S. vs. drug cocktails made up of combinations of ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4856 protocols, and 10 possible experimental measures. The best model found with the original

  1. Mapping chemical structure-activity information of HAART-drug cocktails over complex networks of AIDS epidemiology and socioeconomic data of U.S. counties.

    PubMed

    Herrera-Ibatá, Diana María; Pazos, Alejandro; Orbegozo-Medina, Ricardo Alfredo; Romero-Durán, Francisco Javier; González-Díaz, Humberto

    2015-06-01

    Using computational algorithms to design tailored drug cocktails for highly active antiretroviral therapy (HAART) on specific populations is a goal of major importance for both pharmaceutical industry and public health policy institutions. New combinations of compounds need to be predicted in order to design HAART cocktails. On the one hand, there are the biomolecular factors related to the drugs in the cocktail (experimental measure, chemical structure, drug target, assay organisms, etc.); on the other hand, there are the socioeconomic factors of the specific population (income inequalities, employment levels, fiscal pressure, education, migration, population structure, etc.) to study the relationship between the socioeconomic status and the disease. In this context, machine learning algorithms, able to seek models for problems with multi-source data, have to be used. In this work, the first artificial neural network (ANN) model is proposed for the prediction of HAART cocktails, to halt AIDS on epidemic networks of U.S. counties using information indices that codify both biomolecular and several socioeconomic factors. The data was obtained from at least three major sources. The first dataset included assays of anti-HIV chemical compounds released to ChEMBL. The second dataset is the AIDSVu database of Emory University. AIDSVu compiled AIDS prevalence for >2300 U.S. counties. The third data set included socioeconomic data from the U.S. Census Bureau. Three scales or levels were employed to group the counties according to the location or population structure codes: state, rural urban continuum code (RUCC) and urban influence code (UIC). An analysis of >130,000 pairs (network links) was performed, corresponding to AIDS prevalence in 2310 counties in U.S. vs. drug cocktails made up of combinations of ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4856 protocols, and 10 possible experimental measures. The best model found with the original

  2. Viral proteases as targets for drug design.

    PubMed

    Skoreński, Marcin; Sieńczyk, Marcin

    2013-01-01

    In order to productively infect a host, viruses must enter the cell and force host cell replication mechanisms to produce new infectious virus particles. The success of this process unfortunately results in disease progression and, in the case of infection with many viral species, may cause mortality. The discoveries of Louis Pasteur and Edward Jenner led to one of the greatest advances in modern medicine - the development of vaccines that generate long-lasting memory immune responses to combat viral infection. Widespread use of vaccines has reduced mortality and morbidity associated with viral infection and, in some cases, has completely eradicated virus from the human population. Unfortunately, several viral species maintain a significant ability to mutate and "escape" vaccine-induced immune responses. Thus, novel anti-viral agents are required for treatment and prevention of viral disease. Targeting proteases that are crucial in the viral life cycle has proven to be an effective method to control viral infection, and this avenue of investigation continues to generate anti-viral treatments. Herein, we provide the reader with a brief history as well as a comprehensive review of the most recent advances in the design and synthesis of viral protease inhibitors. PMID:23016690

  3. Enhancements to the Design Manager's Aide for Intelligent Decomposition (DeMAID)

    NASA Technical Reports Server (NTRS)

    Rogers, James L.; Barthelemy, Jean-Francois M.

    1992-01-01

    This paper discusses the addition of two new enhancements to the program Design Manager's Aide for Intelligent Decomposition (DeMAID). DeMAID is a knowledge-based tool used to aid a design manager in understanding the interactions among the tasks of a complex design problem. This is done by ordering the tasks to minimize feedback, determining the participating subsystems, and displaying them in an easily understood format. The two new enhancements include (1) rules for ordering a complex assembly process and (2) rules for determining which analysis tasks must be re-executed to compute the output of one task based on a change in input to that or another task.

  4. Enhancements to the Design Manager's Aide for Intelligent Decomposition (DeMaid)

    NASA Technical Reports Server (NTRS)

    Rogers, James L.; Barthelemy, Jean-Francois M.

    1992-01-01

    This paper discusses the addition of two new enhancements to the program Design Manager's Aide for Intelligent Decomposition (DeMAID). DeMAID is a knowledge-based tool used to aid a design manager in understanding the interactions among the tasks of a complex design problem. This is done by ordering the tasks to minimize feedback, determining the participating subsystems, and displaying them in an easily understood format. The two new enhancements include (1) rules for ordering a complex assembly process and (2) rules for determining which analysis tasks must be re-executed to compute the output of one task based on a change in input to that or another task.

  5. The feasibility of an efficient drug design method with high-performance computers.

    PubMed

    Yamashita, Takefumi; Ueda, Akihiko; Mitsui, Takashi; Tomonaga, Atsushi; Matsumoto, Shunji; Kodama, Tatsuhiko; Fujitani, Hideaki

    2015-01-01

    In this study, we propose a supercomputer-assisted drug design approach involving all-atom molecular dynamics (MD)-based binding free energy prediction after the traditional design/selection step. Because this prediction is more accurate than the empirical binding affinity scoring of the traditional approach, the compounds selected by the MD-based prediction should be better drug candidates. In this study, we discuss the applicability of the new approach using two examples. Although the MD-based binding free energy prediction has a huge computational cost, it is feasible with the latest 10 petaflop-scale computer. The supercomputer-assisted drug design approach also involves two important feedback procedures: The first feedback is generated from the MD-based binding free energy prediction step to the drug design step. While the experimental feedback usually provides binding affinities of tens of compounds at one time, the supercomputer allows us to simultaneously obtain the binding free energies of hundreds of compounds. Because the number of calculated binding free energies is sufficiently large, the compounds can be classified into different categories whose properties will aid in the design of the next generation of drug candidates. The second feedback, which occurs from the experiments to the MD simulations, is important to validate the simulation parameters. To demonstrate this, we compare the binding free energies calculated with various force fields to the experimental ones. The results indicate that the prediction will not be very successful, if we use an inaccurate force field. By improving/validating such simulation parameters, the next prediction can be made more accurate. PMID:25757485

  6. The feasibility of an efficient drug design method with high-performance computers.

    PubMed

    Yamashita, Takefumi; Ueda, Akihiko; Mitsui, Takashi; Tomonaga, Atsushi; Matsumoto, Shunji; Kodama, Tatsuhiko; Fujitani, Hideaki

    2015-01-01

    In this study, we propose a supercomputer-assisted drug design approach involving all-atom molecular dynamics (MD)-based binding free energy prediction after the traditional design/selection step. Because this prediction is more accurate than the empirical binding affinity scoring of the traditional approach, the compounds selected by the MD-based prediction should be better drug candidates. In this study, we discuss the applicability of the new approach using two examples. Although the MD-based binding free energy prediction has a huge computational cost, it is feasible with the latest 10 petaflop-scale computer. The supercomputer-assisted drug design approach also involves two important feedback procedures: The first feedback is generated from the MD-based binding free energy prediction step to the drug design step. While the experimental feedback usually provides binding affinities of tens of compounds at one time, the supercomputer allows us to simultaneously obtain the binding free energies of hundreds of compounds. Because the number of calculated binding free energies is sufficiently large, the compounds can be classified into different categories whose properties will aid in the design of the next generation of drug candidates. The second feedback, which occurs from the experiments to the MD simulations, is important to validate the simulation parameters. To demonstrate this, we compare the binding free energies calculated with various force fields to the experimental ones. The results indicate that the prediction will not be very successful, if we use an inaccurate force field. By improving/validating such simulation parameters, the next prediction can be made more accurate.

  7. Designer lipids for drug delivery: from heads to tails

    PubMed Central

    Kohli, Aditya G.; Kierstead, Paul H.; Venditto, Vincent J.; Walsh, Colin L.; Szoka, Francis C.

    2014-01-01

    For four decades, liposomes composed of both naturally occurring and synthetic lipids have been investigated as delivery vehicles for low molecular weight and macromolecular drugs. These studies paved the way for the clinical and commercial success of a number of liposomal drugs, each of which required a tailored formulation; one liposome size does not fit all drugs! Instead, the physicochemical properties of the liposome must be matched to the pharmacology of the drug. An extensive biophysical literature demonstrates that varying lipid composition can influence the size, membrane stability, in vivo interactions, and drug release properties of a liposome. In this review we focus on recently described synthetic lipid headgroups, linkers and hydrophobic domains that can provide control over the intermolecular forces, phase preference, and macroscopic behavior of liposomes. These synthetic lipids further our understanding of lipid biophysics, promote targeted drug delivery, and improve liposome stability. We further highlight the immune reactivity of novel synthetic headgroups as a key design consideration. For instance it was originally thought that synthetic PEGylated lipids were immunologically inert; however, it’s been observed that under certain conditions PEGylated lipids induce humoral immunity. Such immune activation may be a limitation to the use of other engineered lipid headgroups for drug delivery. In addition to the potential immunogenicity of engineered lipids, future investigations on liposome drugs in vivo should pay particular attention to the location and dynamics of payload release. PMID:24816069

  8. 21 CFR 316.28 - Publication of orphan-drug designations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the drug and the date of the granting of orphan-drug designation; (c) The rare disease or condition... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Publication of orphan-drug designations. 316.28 Section 316.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  9. 21 CFR 316.29 - Revocation of orphan-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... (c) Where a drug has been designated as an orphan drug because the prevalence of a disease or... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Revocation of orphan-drug designation. 316.29 Section 316.29 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  10. The molecule evoluator. An interactive evolutionary algorithm for the design of drug-like molecules.

    PubMed

    Lameijer, Eric-Wubbo; Kok, Joost N; Bäck, Thomas; Ijzerman, Ad P

    2006-01-01

    We developed a software tool to design drug-like molecules, the "Molecule Evoluator", which we introduce and describe here. An atom-based evolutionary approach was used allowing both several types of mutation and crossover to occur. The novelty, we claim, is the unprecedented interactive evolution, in which the user acts as a fitness function. This brings a human being's creativity, implicit knowledge, and imagination into the design process, next to the more standard chemical rules. Proof-of-concept was demonstrated in a number of ways, both computationally and in the lab. Thus, we synthesized a number of compounds designed with the aid of the Molecule Evoluator. One of these is described here, a new chemical entity with activity on alpha-adrenergic receptors.

  11. 21 CFR 316.20 - Content and format of a request for orphan-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... designation of a drug for a specified rare disease or condition shall submit each request in the form and... and obtain orphan-drug designation for the subsequent drug for the same rare disease or condition if.... More than one sponsor may receive orphan-drug designation of the same drug for the same rare disease...

  12. 21 CFR 316.40 - Treatment use of a designated orphan drug.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Treatment use of a designated orphan drug. 316.40... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Open Protocols for Investigations § 316.40 Treatment use of a designated orphan drug. Prospective investigators seeking to obtain treatment use of designated orphan...

  13. [Design of the novel dipeptide neuropsychotropic drug preparations].

    PubMed

    Gudasheva, T A; Skoldinov, A P

    2003-01-01

    The paper considers a new strategy in the field of neuropsychotropic dipeptide drug design, the main points being as follows: (i) determination of the structural elements of dipeptides, such as fragments of amino acid side radicals and peptide bonds, in nonpeptide drugs; (ii) design of peptide analogs topologically close to the drug; (iii) synthesis and activity testing of these analogs; (iv) determination of the corresponding endogenous neuropeptide among the known neuropeptides or identification of the new neuropeptides in the brain of experimental animals. Using this approach, new pyroglutamyl- and prolyl-containing dipeptides were obtained based on the structure of the well-known classical nootropic drug piracetam. The new drugs exhibit nootropic activity in doses 100-10,000 times lower than those of piracetam. The structure of most active pyroglutamyl dipeptide pGlu-Asn-NH2 coincides with that of the N-end fragment of the endogenous memory peptide AVP(4-9). Noopept (N-phenylacetylprolylglycine ethyl ester), patented in Russia and USA as a new nootropic drug, is currently under stage 2 of successful clinical trials. The main metabolite of noopept, cyclo-Pro-Gly, is identical to the endogenous dipeptide designed in this work and is most close analog of piracetam with respect to pharmacological activity. The universal character of the proposed strategy is demonstrated by the design of active dipeptide analogs of an atypical neuroleptic drug sulpiride. As a result, a potential dipeptide neuroleptic dilept was obtained, which has been patented in Russia and now passes broad preclinical trials. PMID:12962042

  14. Nanobiological studies on drug design using molecular mechanic method

    PubMed Central

    Ghaheh, Hooria Seyedhosseini; Mousavi, Maryam; Araghi, Mahmood; Rasoolzadeh, Reza; Hosseini, Zahra

    2015-01-01

    Background: Influenza H1N1 is very important worldwide and point mutations that occur in the virus gene are a threat for the World Health Organization (WHO) and druggists, since they could make this virus resistant to the existing antibiotics. Influenza epidemics cause severe respiratory illness in 30 to 50 million people and kill 250,000 to 500,000 people worldwide every year. Nowadays, drug design is not done through trial and error because of its cost and waste of time; therefore bioinformatics studies is essential for designing drugs. Materials and Methods: This paper, infolds a study on binding site of Neuraminidase (NA) enzyme, (that is very important in drug design) in 310K temperature and different dielectrics, for the best drug design. Information of NA enzyme was extracted from Protein Data Bank (PDB) and National Center for Biotechnology Information (NCBI) websites. The new sequences of N1 were downloaded from the NCBI influenza virus sequence database. Drug binding sites were assimilated and homologized modeling using Argus lab 4.0, HyperChem 6.0 and Chem. D3 softwares. Their stability was assessed in different dielectrics and temperatures. Result: Measurements of potential energy (Kcal/mol) of binding sites of NA in different dielectrics and 310K temperature revealed that at time step size = 0 pSec drug binding sites have maximum energy level and at time step size = 100 pSec have maximum stability and minimum energy. Conclusions: Drug binding sites are more dependent on dielectric constants rather than on temperature and the optimum dielectric constant is 39/78. PMID:26605248

  15. Training Drug Treatment Staff in the Age of AIDS: A Frontline Perspective. Report of a Meeting (April 1989). Clinical Report Series.

    ERIC Educational Resources Information Center

    Ashery, Rebecca S., Ed.

    In April 1989, the National Institute on Drug Abuse (NIDA) convened a meeting of 17 Acquired Immune Deficiency Syndrome (AIDS) education and training experts to discuss AIDS and substance abuse training and to examine NIDA-initiated training efforts. Participants were asked to develop specific recommendations for NIDA regarding its role in…

  16. Designing drug regimens for special intensive care unit populations

    PubMed Central

    Erstad, Brian L

    2015-01-01

    This review is intended to help clinicians design drug regimens for special populations of critically ill patients with extremes of body size, habitus and composition that make drug choice or dosing particularly challenging due to the lack of high-level evidence on which to make well-informed clinical decisions. The data sources included a literature search of MEDLINE and EMBASE with reviews of reference lists of retrieved articles. Abstracts of original research investigations and review papers were reviewed for their relevance to drug choice or dosing in the following special critically ill populations: patients with more severe forms of bodyweight or height, patients with amputations or missing limbs, pregnant patients, and patients undergoing extracorporeal membrane oxygenation or plasma exchange. Relevant papers were retrieved and evaluated, and their associated reference lists were reviewed for citations that may have been missed through the electronic search strategy. Relevant original research investigations and review papers that could be used to formulate general principles for drug choice or dosing in special populations of critically ill patients were extracted. Randomized studies with clinically relevant endpoints were not available for performing quantitative analyses. Critically ill patients with changes in body size, habitus and composition require special consideration when designing medication regimens, but there is a paucity of literature on which to make drug-specific, high-level evidence-based recommendations. Based on the evidence that is available, general recommendations are provided for drug choice or dosing in special critically ill populations. PMID:25938029

  17. Computer-Aided Designed, 3-Dimensionally Printed Porous Tissue Bioscaffolds For Craniofacial Soft Tissue Reconstruction

    PubMed Central

    Zopf, David A.; Mitsak, Anna G.; Flanagan, Colleen L.; Wheeler, Matthew; Green, Glenn E.; Hollister, Scott J.

    2016-01-01

    Objectives To determine the potential of integrated image-based Computer Aided Design (CAD) and 3D printing approach to engineer scaffolds for head and neck cartilaginous reconstruction for auricular and nasal reconstruction. Study Design Proof of concept revealing novel methods for bioscaffold production with in vitro and in vivo animal data. Setting Multidisciplinary effort encompassing two academic institutions. Subjects and Methods DICOM CT images are segmented and utilized in image-based computer aided design to create porous, anatomic structures. Bioresorbable, polycaprolactone scaffolds with spherical and random porous architecture are produced using a laser-based 3D printing process. Subcutaneous in vivo implantation of auricular and nasal scaffolds was performed in a porcine model. Auricular scaffolds were seeded with chondrogenic growth factors in a hyaluronic acid/collagen hydrogel and cultured in vitro over 2 months duration. Results Auricular and nasal constructs with several microporous architectures were rapidly manufactured with high fidelity to human patient anatomy. Subcutaneous in vivo implantation of auricular and nasal scaffolds resulted in excellent appearance and complete soft tissue ingrowth. Histologic analysis of in vitro scaffolds demonstrated native appearing cartilaginous growth respecting the boundaries of the scaffold. Conclusions Integrated image-based computer-aided design (CAD) and 3D printing processes generated patient-specific nasal and auricular scaffolds that supported cartilage regeneration. PMID:25281749

  18. Design Features of Drug-Drug Interaction Trials Between Antivirals and Oral Contraceptives.

    PubMed

    Ayala, Ruben C; Arya, Vikram; Younis, Islam R

    2016-05-01

    The aim of this work was to explore the major design features of drug-drug interaction trials between antiviral medications (AVs) and oral contraceptives (OCs). Information on these trials (n = 27) was collected from approved drug labels and clinical pharmacology reviews conducted by the U.S. Food and Drug Administration. The primary objective of all trials was to evaluate changes in OC exposure following the coadministration of AVs. In addition, an evaluation of potential pharmacodynamic interaction was performed in 10 of these trials. Twenty-two trials were open label with a fixed-sequence design, and 5 trials used a double-blind crossover design. The trials were conducted using one, two, or three 28-day ovulatory cycles in 10, 8, and 9 trials, respectively. Only 1 trial enrolled HIV-infected women. The median number of women in a trial was 20 (range, 12 to 52). Norethindrone/ethinyl estradiol (EE) combination was the most commonly used OC (n = 16, 59%) followed by norgestimate/EE (n = 9, 33%). Labeling recommendations were based on exposure changes in 25 cases and on safety observations in the trial in 2 cases. In conclusion, a wide variety of trial designs was used, and there is no preferred design. The answer to the exposure question can be achieved using multiple designs.

  19. An introduction to quantum chemical methods applied to drug design.

    PubMed

    Stenta, Marco; Dal Peraro, Matteo

    2011-06-01

    The advent of molecular medicine allowed identifying the malfunctioning of subcellular processes as the source of many diseases. Since then, drugs are not only discovered, but actually designed to fulfill a precise task. Modern computational techniques, based on molecular modeling, play a relevant role both in target identification and drug lead development. By flanking and integrating standard experimental techniques, modeling has proven itself as a powerful tool across the drug design process. The success of computational methods depends on a balance between cost (computation time) and accuracy. Thus, the integration of innovative theories and more powerful hardware architectures allows molecular modeling to be used as a reliable tool for rationalizing the results of experiments and accelerating the development of new drug design strategies. We present an overview of the most common quantum chemistry computational approaches, providing for each one a general theoretical introduction to highlight limitations and strong points. We then discuss recent developments in software and hardware resources, which have allowed state-of-the-art of computational quantum chemistry to be applied to drug development.

  20. Learning to design resistance proof drugs from folding

    NASA Astrophysics Data System (ADS)

    Broglia, R. A.

    2009-01-01

    Learning how proteins fold will hardly have any impact on the way conventional — active site centered — drugs are designed. On the other hand, this knowledge is proving instrumental in defining a new paradigm for the identification of drugs against any target protein: folding inhibition. Targeting folding renders drugs less susceptible to spontaneous genetic mutations that in many cases, notably in connection with retroviruses like the Human Immunodeficiency Virus (HIV), can abrogate drug effect. The progress which has taken place during the last years to understand which are the sequences of amino acids which code for a protein, and how to read from these sequences the associated three-dimensional, biologically active, native structure, constitutes the main subject of the present paper. From this narrative the idea of folding inhibitors emerges both naturally and, to some extent, inescapably.

  1. Anti-Inflammatory Drug Design Using a Molecular Hybridization Approach

    PubMed Central

    Bosquesi, Priscila Longhin; Melo, Thais Regina Ferreira; Vizioli, Ednir Oliveira; dos Santos, Jean Leandro; Chung, Man Chin

    2011-01-01

    The design of new drugs with better physiochemical properties, adequate absorption, distribution, metabolism, and excretion, effective pharmacologic potency and lacking toxicity remains is a challenge. Inflammation is the initial trigger of several different diseases, such as Alzheimer's disease, asthma, atherosclerosis, colitis, rheumatoid arthritis, depression, cancer; and disorders such as obesity and sexual dysfunction. Although inflammation is not the direct cause of these disorders, inflammatory processes often increase related pain and suffering. New anti-inflammatory drugs developed using molecular hybridization techniques to obtain multiple-ligand drugs can act at one or multiple targets, allowing for synergic action and minimizing toxicity. This work is a review of new anti-inflammatory drugs developed using the molecular modification approach.

  2. The significance of chirality in drug design and development.

    PubMed

    Brooks, W H; Guida, W C; Daniel, K G

    2011-01-01

    Proteins are often enantioselective towards their binding partners. When designing small molecules to interact with these targets, one should consider stereoselectivity. As considerations for exploring structure space evolve, chirality is increasingly important. Binding affinity for a chiral drug can differ for diastereomers and between enantiomers. For the virtual screening and computational design stage of drug development, this problem can be compounded by incomplete stereochemical information in structure libraries leading to a "coin toss" as to whether or not the "ideal" chiral structure is present. Creating every stereoisomer for each chiral compound in a structure library leads to an exponential increase in the number of structures resulting in potentially unmanageable file sizes and screening times. Therefore, only key chiral structures, enantiomeric pairs based on relative stereochemistry need be included, and lead to a compromise between exploration of chemical space and maintaining manageable libraries. In clinical environments, enantiomers of chiral drugs can have reduced, no, or even deleterious effects. This underscores the need to avoid mixtures of compounds and focus on chiral synthesis. Governmental regulations emphasizing the need to monitor chirality in drug development have increased. The United States Food and Drug Administration issued guidelines and policies in 1992 concerning the development of chiral compounds. These guidelines require that absolute stereochemistry be known for compounds with chiral centers and that this information should be established early in drug development in order that the analysis can be considered valid. From exploration of structure space to governmental regulations it is clear that the question of chirality in drug design is of vital importance. PMID:21291399

  3. The significance of chirality in drug design and development.

    PubMed

    Brooks, W H; Guida, W C; Daniel, K G

    2011-01-01

    Proteins are often enantioselective towards their binding partners. When designing small molecules to interact with these targets, one should consider stereoselectivity. As considerations for exploring structure space evolve, chirality is increasingly important. Binding affinity for a chiral drug can differ for diastereomers and between enantiomers. For the virtual screening and computational design stage of drug development, this problem can be compounded by incomplete stereochemical information in structure libraries leading to a "coin toss" as to whether or not the "ideal" chiral structure is present. Creating every stereoisomer for each chiral compound in a structure library leads to an exponential increase in the number of structures resulting in potentially unmanageable file sizes and screening times. Therefore, only key chiral structures, enantiomeric pairs based on relative stereochemistry need be included, and lead to a compromise between exploration of chemical space and maintaining manageable libraries. In clinical environments, enantiomers of chiral drugs can have reduced, no, or even deleterious effects. This underscores the need to avoid mixtures of compounds and focus on chiral synthesis. Governmental regulations emphasizing the need to monitor chirality in drug development have increased. The United States Food and Drug Administration issued guidelines and policies in 1992 concerning the development of chiral compounds. These guidelines require that absolute stereochemistry be known for compounds with chiral centers and that this information should be established early in drug development in order that the analysis can be considered valid. From exploration of structure space to governmental regulations it is clear that the question of chirality in drug design is of vital importance.

  4. Computer-aided analysis and design of the shape rolling process for producing turbine engine airfoils

    NASA Technical Reports Server (NTRS)

    Lahoti, G. D.; Akgerman, N.; Altan, T.

    1978-01-01

    Mild steel (AISI 1018) was selected as model cold rolling material and Ti-6A1-4V and Inconel 718 were selected as typical hot rolling and cold rolling alloys, respectively. The flow stress and workability of these alloys were characterized and friction factor at the roll/workpiece interface was determined at their respective working conditions by conducting ring tests. Computer-aided mathematical models for predicting metal flow and stresses, and for simulating the shape rolling process were developed. These models utilized the upper bound and the slab methods of analysis, and were capable of predicting the lateral spread, roll separating force, roll torque, and local stresses, strains and strain rates. This computer-aided design system was also capable of simulating the actual rolling process, and thereby designing the roll pass schedule in rolling of an airfoil or a similar shape.

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

    PubMed

    Weaver, Ian N; Weaver, Donald F

    2013-10-01

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

  6. The Effectiveness of Drug Abuse Treatment: Implications for Controlling AIDS/HIV Infection. Background Paper 3.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Office of Technology Assessment.

    This background paper examines evidence for the effectiveness of treatment for drug abuse and evaluates the role of drug abuse treatment as a strategy to prevent Human Immunodeficiency Virus (HIV) spread. Because most intravenous (IV) drug users are not in treatment, the study also examines other approaches to HIV prevention. The remainder of the…

  7. Computer-Aided Design/Manufacturing (CAD/M) for high-speed interconnect

    NASA Astrophysics Data System (ADS)

    Santoski, N. F.

    1981-10-01

    The objective of the Computer-Aided Design/Manufacturing (CAD/M) for High-Speed Interconnect Program study was to assess techniques for design, analysis and fabrication of interconnect structures between high-speed logic ICs that are clocked in the 200 MHz to 5 GHz range. Interconnect structure models were investigated and integrated with existing device models. Design rules for interconnects were developed in terms of parameters that can be installed in software that is used for the design, analysis and fabrication of circuits. To implement these design rules in future software development, algorithms and software development techniques were defined. Major emphasis was on Printed Wiring Board and hybrid level circuits as opposed to monolithic chips. Various packaging schemes were considered, including controlled impedance lines in the 50 to 200 ohms range where needed. The design rules developed are generic in nature, in that various architecture classes and device technologies were considered.

  8. Mandibular Reconstruction Using a Custom-Made Titanium Prosthesis: A Case Report on the Use of Virtual Surgical Planning and Computer-Aided Design/Computer-Aided Manufacturing.

    PubMed

    Ow, Andrew; Tan, Winston; Pienkowski, Lukasz

    2016-09-01

    The use of virtual surgical planning and computer-aided design/computer-aided manufacturing has been reported to enhance the planning for the reconstruction of mandibular continuity defects. This case report illustrates the use of this technology in the fabrication of a custom-made titanium prosthesis to restore a segmental mandibular defect. The design specifications and sequence of the custom-made titanium prosthesis are discussed. Although successful in this case, there are limitations in its application and case selection is of vital importance. PMID:27516841

  9. Mandibular Reconstruction Using a Custom-Made Titanium Prosthesis: A Case Report on the Use of Virtual Surgical Planning and Computer-Aided Design/Computer-Aided Manufacturing.

    PubMed

    Ow, Andrew; Tan, Winston; Pienkowski, Lukasz

    2016-09-01

    The use of virtual surgical planning and computer-aided design/computer-aided manufacturing has been reported to enhance the planning for the reconstruction of mandibular continuity defects. This case report illustrates the use of this technology in the fabrication of a custom-made titanium prosthesis to restore a segmental mandibular defect. The design specifications and sequence of the custom-made titanium prosthesis are discussed. Although successful in this case, there are limitations in its application and case selection is of vital importance.

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

    ERIC Educational Resources Information Center

    Prausnitz, Mark R.; Bommarius, Andreas S.

    2011-01-01

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

  11. A Prospective Method to Guide Small Molecule Drug Design

    ERIC Educational Resources Information Center

    Johnson, Alan T.

    2015-01-01

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

  12. Tools to aid the specification and design of flight software, appendix B

    NASA Technical Reports Server (NTRS)

    Bristow, G.

    1980-01-01

    The tasks that are normally performed during the specification and architecture design stages of software development are identified. Ways that tools could perform, or aid the performance, of such tasks are also identified. Much of the verification and analysis that is suggested is currently rarely performed during these early stages, but it is believed that this analysis should be done as early as possible so as to detect errors as early as possible.

  13. Computer-aided design and drafting visualization of anatomical structure of the human eye and orbit

    NASA Astrophysics Data System (ADS)

    Parshall, Robert F.; Sadler, Lewis L.

    1991-04-01

    A generalized " anatomically standard" eyeball was geometrically modeled on a Computer-Aided Design and Drafting (CADD) workstation based on published conceptual norms of dimension radii of curvature alignments etc. An orbital environment for this model was concurrently prepared by serial section reconstruction of a cadaver specimen. Issues addressed include orienting unregistered sections the utility of interactive CADDsupported visual logic in interpretive decision making and the value of geometric models.

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

    NASA Technical Reports Server (NTRS)

    Thorp, Scott A.

    1992-01-01

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

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

    PubMed

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

    2015-12-01

    Recently, the abuse of designer drugs has become a social problem. Designer drugs are created by modifying part of the chemical structure of drugs that have already been categorized as illegal, thereby creating a different chemical compound in order to evade Pharmaceutical Affairs Law regulations. The new comprehensive system for designating illegal drug components has been in effect since March 2013, and many designer drugs can now be regulated. We conducted an online questionnaire survey of people with a history of designer drug use to elucidate the effects of the new system on the abuse of designer drugs and to identify potential future problems. Over half the subjects obtained designer drugs only before the new system was implemented. Awareness of the system was significantly lower among subjects who obtained designer drugs for the first time after its introduction than those who obtained the drugs only before its implementation. Due to the new system, all methods of acquiring designer drugs saw decreases in activity. However, the ratio of the acquisition of designer drugs via the Internet increased. Since over 50% of the subjects never obtained designer drugs after the new system was introduced, goals that aimed to make drug procurement more difficult were achieved. However, awareness of the new system among subjects who obtained designer drugs after the new system was introduced was significantly low. Therefore, fostering greater public awareness of the new system is necessary. The results of the questionnaire also suggested that acquiring designer drugs through the Internet has hardly been affected by the new system. We strongly hope that there will be a greater push to restrict the sale of designer drugs on the Internet in the near future. PMID:26975077

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

    PubMed

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

    2015-12-01

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

  17. Next-Generation Antimalarial Drugs: Hybrid Molecules as a New Strategy in Drug Design

    PubMed Central

    Muregi, Francis W; Ishih, Akira

    2010-01-01

    Malaria is a disease that affects nearly 40% of the global population, and chemotherapy remains the mainstay of its control strategy. The global malaria situation is increasingly being exacerbated by the emergence of drug resistance to most of the available antimalarials, necessitating search for novel drugs. A recent rational approach of antimalarial drug design characterized as “covalent bitherapy” involves linking two molecules with individual intrinsic activity into a single agent, thus packaging dual-activity into a single hybrid molecule. Current research in this field seems to endorse hybrid molecules as the next-generation antimalarial drugs. If the selective toxicity of hybrid prodrugs can be demonstrated in vivo with good bioavailability at the target site in the parasite, it would offer various advantages including dosage compliance, minimized toxicity, ability to design better drug combinations, and cheaper preclinical evaluation while achieving the ultimate object of delaying or circumventing the development of resistance. This review is focused on several hybrid molecules that have been developed, with particular emphasis on those deemed to have high potential for development for clinical use. Drug Dev Res 71: 20–32, 2010. © 2009 Wiley-Liss, Inc. PMID:21399701

  18. IDEAS: A multidisciplinary computer-aided conceptual design system for spacecraft

    NASA Technical Reports Server (NTRS)

    Ferebee, M. J., Jr.

    1984-01-01

    During the conceptual development of advanced aerospace vehicles, many compromises must be considered to balance economy and performance of the total system. Subsystem tradeoffs may need to be made in order to satisfy system-sensitive attributes. Due to the increasingly complex nature of aerospace systems, these trade studies have become more difficult and time-consuming to complete and involve interactions of ever-larger numbers of subsystems, components, and performance parameters. The current advances of computer-aided synthesis, modeling and analysis techniques have greatly helped in the evaluation of competing design concepts. Langley Research Center's Space Systems Division is currently engaged in trade studies for a variety of systems which include advanced ground-launched space transportation systems, space-based orbital transfer vehicles, large space antenna concepts and space stations. The need for engineering analysis tools to aid in the rapid synthesis and evaluation of spacecraft has led to the development of the Interactive Design and Evaluation of Advanced Spacecraft (IDEAS) computer-aided design system. The ADEAS system has been used to perform trade studies of competing technologies and requirements in order to pinpoint possible beneficial areas for research and development. IDEAS is presented as a multidisciplinary tool for the analysis of advanced space systems. Capabilities range from model generation and structural and thermal analysis to subsystem synthesis and performance analysis.

  19. Semantic Web Ontology and Data Integration: a Case Study in Aiding Psychiatric Drug Repurposing.

    PubMed

    Liang, Chen; Sun, Jingchun; Tao, Cui

    2016-01-01

    Despite ongoing progress towards treating mental illness, there remain significant difficulties in selecting probable candidate drugs from the existing database. We describe an ontology - oriented approach aims to represent the nexus between genes, drugs, phenotypes, symptoms, and diseases from multiple information sources. Along with this approach, we report a case study in which we attempted to explore the candidate drugs that effective for both bipolar disorder and epilepsy. We constructed an ontology that incorporates the knowledge between the two diseases and performed semantic reasoning task on the ontology. The reasoning results suggested 48 candidate drugs that hold promise for a further breakthrough. The evaluation was performed and demonstrated the validity of the proposed ontology. The overarching goal of this research is to build a framework of ontology - based data integration underpinning psychiatric drug repurposing. This approach prioritizes the candidate drugs that have potential associations among genes, phenotypes and symptoms, and thus facilitates the data integration and drug repurposing in psychiatric disorders. PMID:27570661

  20. Semantic Web Ontology and Data Integration: a Case Study in Aiding Psychiatric Drug Repurposing.

    PubMed

    Liang, Chen; Sun, Jingchun; Tao, Cui

    2016-01-01

    Despite ongoing progress towards treating mental illness, there remain significant difficulties in selecting probable candidate drugs from the existing database. We describe an ontology - oriented approach aims to represent the nexus between genes, drugs, phenotypes, symptoms, and diseases from multiple information sources. Along with this approach, we report a case study in which we attempted to explore the candidate drugs that effective for both bipolar disorder and epilepsy. We constructed an ontology that incorporates the knowledge between the two diseases and performed semantic reasoning task on the ontology. The reasoning results suggested 48 candidate drugs that hold promise for a further breakthrough. The evaluation was performed and demonstrated the validity of the proposed ontology. The overarching goal of this research is to build a framework of ontology - based data integration underpinning psychiatric drug repurposing. This approach prioritizes the candidate drugs that have potential associations among genes, phenotypes and symptoms, and thus facilitates the data integration and drug repurposing in psychiatric disorders.

  1. Glycoscience -- a new frontier in rational drug design.

    PubMed

    Gornik, Olga; Dumić, Jerka; Flogel, Mirna; Lauc, Gordan

    2006-03-01

    Glycans are the most abundant and most diverse biopolymers in nature. Because of their highly specific interactions with physiological receptors, they participate in many crucial biological processes. All these processes are potential targets for therapeutic intervention, and carbohydrate-based drugs are rapidly being taken up by the modern biotechnology and pharmaceutical industry. Recent developments in the field of glycobiology have overcome the problem of glycan analysis and synthesis; and many compounds based on carbohydrates are now in various stages of clinical trials. This article presents glycoproteins in a new light, as an important biopharmaceutical target, giving an overview of their potential use as therapeutic glycoproteins and proteoglycans, inflammation blockers, cancer therapeutics and vaccines, inhibitors of pathogenic microbes, viral inhibitors and potential aids in the treatment of lysosomal diseases, neurological diseases and transplantation rejection. PMID:16613732

  2. Glycoscience -- a new frontier in rational drug design.

    PubMed

    Gornik, Olga; Dumić, Jerka; Flogel, Mirna; Lauc, Gordan

    2006-03-01

    Glycans are the most abundant and most diverse biopolymers in nature. Because of their highly specific interactions with physiological receptors, they participate in many crucial biological processes. All these processes are potential targets for therapeutic intervention, and carbohydrate-based drugs are rapidly being taken up by the modern biotechnology and pharmaceutical industry. Recent developments in the field of glycobiology have overcome the problem of glycan analysis and synthesis; and many compounds based on carbohydrates are now in various stages of clinical trials. This article presents glycoproteins in a new light, as an important biopharmaceutical target, giving an overview of their potential use as therapeutic glycoproteins and proteoglycans, inflammation blockers, cancer therapeutics and vaccines, inhibitors of pathogenic microbes, viral inhibitors and potential aids in the treatment of lysosomal diseases, neurological diseases and transplantation rejection.

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

    NASA Astrophysics Data System (ADS)

    Lueshen, Eric

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

  4. Drug treatments for schizophrenia: pragmatism in trial design shows lack of progress in drug design.

    PubMed

    Cheng, F; Jones, P B

    2013-09-01

    Aims. The introduction of second generation antipsychotic (SGA) medication over a decade ago led to changes in prescribing practices; these drugs have eclipsed their predecessors as treatments for schizophrenia. However, the metabolic side effects of these newer antipsychotics have been marked and there are increasing concerns as to whether these novel drugs really are superior to their predecessors in terms of the balance between risks and benefits. In this article, we review the literature regarding comparisons between first generation antipsychotic (FGA) and SGA in terms of clinical effectiveness. Methods. Large (n > 150) randomized-controlled trials (RCTs) comparing the effectiveness (efficacy and side effects) of FGA and SGA medications other than clozapine were reviewed, as were meta-analyses that included smaller studies. Results. The superiority in efficacy and reduced extrapyramidal side effects (EPSE) of SGAs is modest, especially when compared with low-dose FGAs. However, the high risk of weight gain and other metabolic disturbances associated with certain SGAs such as olanzapine is markedly higher than the risk with FGAs at the doses used in the trials. Conclusions. The efficacy profiles of various FGAs and SGAs are relatively similar, but their side effects vary between and within classes. Overall, large pragmatic trials of clinical effectiveness indicate that the care used in prescribing and managing drug treatments to ensure tolerability may be more important than the class of drug used.

  5. Microbial biotransformation: a tool for drug designing (Review).

    PubMed

    Pervaiz, I; Ahmad, S; Madni, M A; Ahmad, H; Khaliq, F H

    2013-01-01

    For centuries microbial biotransformation has proved to be an imperative tool in alleviating the production of various chemicals used in food, pharmaceutical, agrochemical and other industries. In the field of phar- maceutical research and development, biotransformation studies have been extensively applied to investigate the metabolism of compounds (leads, lead candidates, etc.) using animal models. The microbial biotransfor- mation phenomenon is then commonly employed in comparing metabolic pathways of drugs and scaling up the metabolites of interest discovered in these animal models for further pharmacological and toxicological evaluation. Microorganisms can conveniently afford drugs difficult obtained via synthesis. The plethora of reported microbial biotransformations along with its added benefits has already invoked further research in bioconversion of novel and structurally complex drugs. This review alternatively discusses the prospect of microbial biotransformation studies as a significant element ameliorating drug discovery and design in terms of cost-effectiveness, environment protection and greater structural diversity as compared to animal models used to study metabolism. To explicate the microbial biotransformation paradigm in drug designing 3 main areas in this aspect have been analyzed: 1--lead expansion: obtaining pharmacologically improved metabo- lites from bioactive molecules; 2--biosynthesis of precursors/intermediates involved in the production of bioactive molecules; 3--resolution of racemic mixture to obtain enantiomers possessing different pharma- cological profiles.

  6. Microbial biotransformation: a tool for drug designing (Review).

    PubMed

    Pervaiz, I; Ahmad, S; Madni, M A; Ahmad, H; Khaliq, F H

    2013-01-01

    For centuries microbial biotransformation has proved to be an imperative tool in alleviating the production of various chemicals used in food, pharmaceutical, agrochemical and other industries. In the field of phar- maceutical research and development, biotransformation studies have been extensively applied to investigate the metabolism of compounds (leads, lead candidates, etc.) using animal models. The microbial biotransfor- mation phenomenon is then commonly employed in comparing metabolic pathways of drugs and scaling up the metabolites of interest discovered in these animal models for further pharmacological and toxicological evaluation. Microorganisms can conveniently afford drugs difficult obtained via synthesis. The plethora of reported microbial biotransformations along with its added benefits has already invoked further research in bioconversion of novel and structurally complex drugs. This review alternatively discusses the prospect of microbial biotransformation studies as a significant element ameliorating drug discovery and design in terms of cost-effectiveness, environment protection and greater structural diversity as compared to animal models used to study metabolism. To explicate the microbial biotransformation paradigm in drug designing 3 main areas in this aspect have been analyzed: 1--lead expansion: obtaining pharmacologically improved metabo- lites from bioactive molecules; 2--biosynthesis of precursors/intermediates involved in the production of bioactive molecules; 3--resolution of racemic mixture to obtain enantiomers possessing different pharma- cological profiles. PMID:25508645

  7. Microbial biotransformation: a tool for drug designing (Review).

    PubMed

    Pervaiz, I; Ahmad, S; Madni, M A; Ahmad, H; Khaliq, F H

    2013-01-01

    For centuries microbial biotransformation has proved to be an imperative tool in alleviating the production of various chemicals used in food, pharmaceutical, agrochemical and other industries. In the field of phar- maceutical research and development, biotransformation studies have been extensively applied to investigate the metabolism of compounds (leads, lead candidates, etc.) using animal models. The microbial biotransfor- mation phenomenon is then commonly employed in comparing metabolic pathways of drugs and scaling up the metabolites of interest discovered in these animal models for further pharmacological and toxicological evaluation. Microorganisms can conveniently afford drugs difficult obtained via synthesis. The plethora of reported microbial biotransformations along with its added benefits has already invoked further research in bioconversion of novel and structurally complex drugs. This review alternatively discusses the prospect of microbial biotransformation studies as a significant element ameliorating drug discovery and design in terms of cost-effectiveness, environment protection and greater structural diversity as compared to animal models used to study metabolism. To explicate the microbial biotransformation paradigm in drug designing 3 main areas in this aspect have been analyzed: 1--lead expansion: obtaining pharmacologically improved metabo- lites from bioactive molecules; 2--biosynthesis of precursors/intermediates involved in the production of bioactive molecules; 3--resolution of racemic mixture to obtain enantiomers possessing different pharma- cological profiles. PMID:25474866

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

    PubMed

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

    2011-02-01

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

  9. Chemogenomic profiling of Plasmodium falciparum as a tool to aid antimalarial drug discovery.

    PubMed

    Pradhan, Anupam; Siwo, Geoffrey H; Singh, Naresh; Martens, Brian; Balu, Bharath; Button-Simons, Katrina A; Tan, Asako; Zhang, Min; Udenze, Kenneth O; Jiang, Rays H Y; Ferdig, Michael T; Adams, John H; Kyle, Dennis E

    2015-01-01

    The spread of Plasmodium falciparum multidrug resistance highlights the urgency to discover new targets and chemical scaffolds. Unfortunately, lack of experimentally validated functional information about most P. falciparum genes remains a strategic hurdle. Chemogenomic profiling is an established tool for classification of drugs with similar mechanisms of action by comparing drug fitness profiles in a collection of mutants. Inferences of drug mechanisms of action and targets can be obtained by associations between shifts in drug fitness and specific genetic changes in the mutants. In this screen, P. falciparum, piggyBac single insertion mutants were profiled for altered responses to antimalarial drugs and metabolic inhibitors to create chemogenomic profiles. Drugs targeting the same pathway shared similar response profiles and multiple pairwise correlations of the chemogenomic profiles revealed novel insights into drugs' mechanisms of action. A mutant of the artemisinin resistance candidate gene - "K13-propeller" gene (PF3D7_1343700) exhibited increased susceptibility to artemisinin drugs and identified a cluster of 7 mutants based on similar enhanced responses to the drugs tested. Our approach of chemogenomic profiling reveals artemisinin functional activity, linked by the unexpected drug-gene relationships of these mutants, to signal transduction and cell cycle regulation pathways.

  10. Improving drug retention in liposomes by aging with the aid of glucose.

    PubMed

    Zhang, Wenli; Falconer, James R; Baguley, Bruce C; Shaw, John P; Kanamala, Manju; Xu, Hongtao; Wang, Guangji; Liu, Jianping; Wu, Zimei

    2016-05-30

    This paper describes a novel method to improve drug retention in liposomes for the poorly water-soluble (lipophilic) model drug asulacrine (ASL). ASL was loaded in the aqueous phase of liposomes and the effects of aging conditions and drug loading levels on drug retention were investigated using an in vitro bio-relevant drug release test established in this study. The status of intra-liposomal drug was investigated using differential scanning calorimetry (DSC) and cryo-transmission electron microscopy (cryo-TEM). Pharmacokinetics and venous tolerance of the formulations were simultaneously studied in rabbits following one-hour intravenous infusion via the ear vein. The presence of glucose during aging was found to be crucial to accelerate drug precipitation and to stabilize the liposomal membrane with high drug loading (8.9% over 4.5% w/w) as a prerequisite. Although no drug crystals were detected, DSC showed a lower phase-transition peak in the glucose-assisted aged ASL-liposomes, indicating interaction of phospholipids with the sugar. Cryo-TEM revealed more 'coffee bean' like drug precipitate in the ASL-liposomes aged in the glucose solution. In rabbits, these liposomes gave rise to a 1.9 times longer half-life than the fresh liposomes, with no venous irritation observed. Inducing and stabilizing drug precipitation in the liposome cores by aging in the presence of sugar provided an easy approach to improve drug retention in liposomes. The study also highlighted the importance of bio-relevance of in vitro release methods to predict in vivo drug release. PMID:27021465

  11. Design model of computerized personal decision aid for youth: An expert review

    NASA Astrophysics Data System (ADS)

    Sarif, Siti Mahfuzah; Ibrahim, Norfiza; Shiratuddin, Norshuhada

    2016-08-01

    This paper provides a structured review of a design model of a computerized personal decision aid that is intended for youth, named as YouthPDA Design Model. The proposed design model was examined by experts in related areas to ensure the appropriateness of the proposed components and elements, relevancy of the terminologies used, logic of the flow, usability, and practicality of the design model towards development of YouthPDA application. Seven experts from related areas were involved in the evaluation. Discussions on the findings obtained from the expert review are included in this paper. Finally, a revised design model of YouthPDA is proposed as main guidance to develop YouthPDA application.

  12. Update and overview of practical epidemiologic aspects of HIV/AIDS among injection drug users in the United States.

    PubMed

    Santibanez, Scott S; Garfein, Richard S; Swartzendruber, Andrea; Purcell, David W; Paxton, Lynn A; Greenberg, Alan E

    2006-01-01

    In a changing public health landscape in which local, state, and federal agencies must confront threats of bioterrorism, emerging infections, and numerous chronic diseases, transmission of HIV among injection drug users (IDUs) continues to be an important public health issue and one of the driving forces behind the HIV epidemic. Using a computerized MEDLINE search of published articles from January 1981 through October 2005, we conducted a literature review of practical epidemiologic aspects of HIV/AIDS among IDUs in the United States. Although recent trends indicate a decline in the proportion of newly diagnosed HIV infections associated with injection drug use, drug-use behaviors overall still account for 32% of new HIV diagnoses. Factors in addition to syringe sharing contribute to HIV transmission among IDUs: risky sexual behaviors, sharing of drug preparation equipment and drug solutions, and contextual and social factors. Promising approaches for HIV prevention include rapid HIV testing, office-based substance abuse treatment, behavioral interventions, improved communication about syringe exchange programs, and case management. HIV among IDUs continues to be an important public health problem in the 21st century. It is imperative that public health agencies continue to monitor and combat the HIV epidemic among IDUs to ensure that hard-won gains will not be eroded. PMID:16736357

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

    PubMed Central

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

    2015-01-01

    The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. PMID:25765758

  14. Metalloporphyrin catalysts for oxygen reduction developed using computer-aided molecular design

    SciTech Connect

    Ryba, G.N.; Hobbs, J.D.; Shelnutt, J.A.

    1996-04-01

    The objective of this project is the development of a new class of metalloporphyrin materials used as catalsyts for use in fuel cell applications. The metalloporphyrins are excellent candidates for use as catalysts at both the anode and cathode. The catalysts reduce oxygen in 1 M potassium hydroxide, as well as in 2 M sulfuric acid. Covalent attachment to carbon supports is being investigated. The computer-aided molecular design is an iterative process, in which experimental results feed back into the design of future catalysts.

  15. 21 CFR 516.30 - Annual reports for a MUMS-designated drug.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species...

  16. 21 CFR 516.30 - Annual reports for a MUMS-designated drug.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species...

  17. 21 CFR 516.20 - Content and format of a request for MUMS-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Content and format of a request for MUMS-drug designation. 516.20 Section 516.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.20 Content and format of...

  18. 21 CFR 516.30 - Annual reports for a MUMS-designated drug.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species...

  19. [The Beers List as an aid to prevent adverse drug reactions in elderly patients].

    PubMed

    Vingerhoets, R W; van Marum, R J; Jansen, P A F

    2005-09-17

    Elderly patients are highly susceptible for developing adverse drug reactions (ADR) that can lead to hospitalisation or death. Most of these ADR can be prevented if doctors adjust their prescriptions. Beers et al. have developed a list of drugs that should not be prescribed to elderly patients since they are known for their association with serious ADR. In The Netherlands, 20% of elderly patients receive drugs that are in the so-called Beers list. Although the Beers list has not been adjusted to the Dutch situation, avoidance of these drugs may reduce drug-related hospital admittance. Development of an improved list of drugs that should not be prescribed to elderly patients is needed that is applicable to The Netherlands. PMID:16201599

  20. Semantic Web Ontology and Data Integration: a Case Study in Aiding Psychiatric Drug Repurposing.

    PubMed

    Liang, Chen; Sun, Jingchun; Tao, Cui

    2015-01-01

    There remain significant difficulties selecting probable candidate drugs from existing databases. We describe an ontology-oriented approach to represent the nexus between genes, drugs, phenotypes, symptoms, and diseases from multiple information sources. We also report a case study in which we attempted to explore candidate drugs effective for bipolar disorder and epilepsy. We constructed an ontology incorporating knowledge between the two diseases and performed semantic reasoning tasks with the ontology. The results suggested 48 candidate drugs that hold promise for further breakthrough. The evaluation demonstrated the validity our approach. Our approach prioritizes the candidate drugs that have potential associations among genes, phenotypes and symptoms, and thus facilitates the data integration and drug repurposing in psychiatric disorders.

  1. Computer-aided design of control systems to meet many requirements

    NASA Technical Reports Server (NTRS)

    Schy, A. A.; Adams, W. M., Jr.; Johnson, K. G.

    1974-01-01

    A method is described for using nonlinear programing in the computer-aided design of airplane control systems. It is assumed that the quality of such systems depends on many criteria. These criteria are included in the constraints vector (instead of attempting to combine them into a single scalar criterion, as is usually done), and the design proceeds through a sequence of nonlinear programing solutions in which the designer varies the specification of sets of requirements levels. The method is applied to design of a lateral stability augmentation system (SAS) for a fighter airplane, in which the requirements vector is chosen from the official handling qualities specifications. Results are shown for several simple SAS configurations designed to obtain desirable handling qualities over all design flight conditions with minimum feedback gains. The choice of the final design for each case is not unique but depends on the designer's decision as to which achievable set of requirements levels represents the best for that system. Results indicate that it may be possible to design constant parameter SAS which can satisfy the most stringent handling qualities requirements for fighter airplanes in all flight conditions. The role of the designer as a decision maker, interacting with the computer program, is discussed. Advantages of this type of designer-computer interaction are emphasized. Desirable extensions of the method are indicated.

  2. Automated a complex computer aided design concept generated using macros programming

    NASA Astrophysics Data System (ADS)

    Rizal Ramly, Mohammad; Asrokin, Azharrudin; Abd Rahman, Safura; Zulkifly, Nurul Ain Md

    2013-12-01

    Changing a complex Computer Aided design profile such as car and aircraft surfaces has always been difficult and challenging. The capability of CAD software such as AutoCAD and CATIA show that a simple configuration of a CAD design can be easily modified without hassle, but it is not the case with complex design configuration. Design changes help users to test and explore various configurations of the design concept before the production of a model. The purpose of this study is to look into macros programming as parametric method of the commercial aircraft design. Macros programming is a method where the configurations of the design are done by recording a script of commands, editing the data value and adding a certain new command line to create an element of parametric design. The steps and the procedure to create a macro programming are discussed, besides looking into some difficulties during the process of creation and advantage of its usage. Generally, the advantages of macros programming as a method of parametric design are; allowing flexibility for design exploration, increasing the usability of the design solution, allowing proper contained by the model while restricting others and real time feedback changes.

  3. Chemogenomic profiling of Plasmodium falciparum as a tool to aid antimalarial drug discovery

    PubMed Central

    Pradhan, Anupam; Siwo, Geoffrey H.; Singh, Naresh; Martens, Brian; Balu, Bharath; Button-Simons, Katrina A.; Tan, Asako; Zhang, Min; Udenze, Kenneth O.; Jiang, Rays H.Y.; Ferdig, Michael T.; Adams, John H.; Kyle, Dennis E.

    2015-01-01

    The spread of Plasmodium falciparum multidrug resistance highlights the urgency to discover new targets and chemical scaffolds. Unfortunately, lack of experimentally validated functional information about most P. falciparum genes remains a strategic hurdle. Chemogenomic profiling is an established tool for classification of drugs with similar mechanisms of action by comparing drug fitness profiles in a collection of mutants. Inferences of drug mechanisms of action and targets can be obtained by associations between shifts in drug fitness and specific genetic changes in the mutants. In this screen, P. falciparum, piggyBac single insertion mutants were profiled for altered responses to antimalarial drugs and metabolic inhibitors to create chemogenomic profiles. Drugs targeting the same pathway shared similar response profiles and multiple pairwise correlations of the chemogenomic profiles revealed novel insights into drugs’ mechanisms of action. A mutant of the artemisinin resistance candidate gene - “K13-propeller” gene (PF3D7_1343700) exhibited increased susceptibility to artemisinin drugs and identified a cluster of 7 mutants based on similar enhanced responses to the drugs tested. Our approach of chemogenomic profiling reveals artemisinin functional activity, linked by the unexpected drug-gene relationships of these mutants, to signal transduction and cell cycle regulation pathways. PMID:26541648

  4. Analysis of Drug Design for a Selection of G Protein-Coupled Neuro- Receptors Using Neural Network Techniques.

    PubMed

    Agerskov, Claus; Mortensen, Rasmus M; Bohr, Henrik G

    2015-01-01

    A study is presented on how well possible drug-molecules can be predicted with respect to their function and binding to a selection of neuro-receptors by the use of artificial neural networks. The ligands investigated in this study are chosen to be corresponding to the G protein-coupled receptors µ-opioid, serotonin 2B (5-HT2B) and metabotropic glutamate D5. They are selected due to the availability of pharmacological drug-molecule binding data for these receptors. Feedback and deep belief artificial neural network architectures (NNs) were chosen to perform the task of aiding drugdesign. This is done by training on structural features, selected using a "minimum redundancy, maximum relevance"-test, and testing for successful prediction of categorized binding strength. An extensive comparison of the neural network performances was made in order to select the optimal architecture. Deep belief networks, trained with greedy learning algorithms, showed superior performance in prediction over the simple feedback NNs. The best networks obtained scores of more than 90 % accuracy in predicting the degree of binding drug molecules to the mentioned receptors and with a maximal Matthew`s coefficient of 0.925. The performance of 8 category networks (8 output classes for binding strength) obtained a prediction accuracy of above 60 %. After training the networks, tests were done on how well the systems could be used as an aid in designing candidate drug molecules. Specifically, it was shown how a selection of chemical characteristics could give the lowest observed IC50 values, meaning largest bio-effect pr. nM substance, around 0.03-0.06 nM. These ligand characteristics could be total number of atoms, their types etc. In conclusion, deep belief networks trained on drug-molecule structures were demonstrated as powerful computational tools, able to aid in drug-design in a fast and cheap fashion, compared to conventional pharmacological techniques.

  5. Analysis of Drug Design for a Selection of G Protein-Coupled Neuro- Receptors Using Neural Network Techniques.

    PubMed

    Agerskov, Claus; Mortensen, Rasmus M; Bohr, Henrik G

    2015-01-01

    A study is presented on how well possible drug-molecules can be predicted with respect to their function and binding to a selection of neuro-receptors by the use of artificial neural networks. The ligands investigated in this study are chosen to be corresponding to the G protein-coupled receptors µ-opioid, serotonin 2B (5-HT2B) and metabotropic glutamate D5. They are selected due to the availability of pharmacological drug-molecule binding data for these receptors. Feedback and deep belief artificial neural network architectures (NNs) were chosen to perform the task of aiding drugdesign. This is done by training on structural features, selected using a "minimum redundancy, maximum relevance"-test, and testing for successful prediction of categorized binding strength. An extensive comparison of the neural network performances was made in order to select the optimal architecture. Deep belief networks, trained with greedy learning algorithms, showed superior performance in prediction over the simple feedback NNs. The best networks obtained scores of more than 90 % accuracy in predicting the degree of binding drug molecules to the mentioned receptors and with a maximal Matthew`s coefficient of 0.925. The performance of 8 category networks (8 output classes for binding strength) obtained a prediction accuracy of above 60 %. After training the networks, tests were done on how well the systems could be used as an aid in designing candidate drug molecules. Specifically, it was shown how a selection of chemical characteristics could give the lowest observed IC50 values, meaning largest bio-effect pr. nM substance, around 0.03-0.06 nM. These ligand characteristics could be total number of atoms, their types etc. In conclusion, deep belief networks trained on drug-molecule structures were demonstrated as powerful computational tools, able to aid in drug-design in a fast and cheap fashion, compared to conventional pharmacological techniques. PMID:26463104

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

    PubMed

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

    2016-04-25

    Computer-aided drug design plays an important role in medicinal chemistry to obtain insights into molecular mechanisms and to prioritize design strategies. Although significant improvement has been made in structure based design, it still remains a key challenge to accurately model and predict induced fit mechanisms. Most of the current available techniques either do not provide sufficient protein conformational sampling or are too computationally demanding to fit an industrial setting. The current study presents a systematic and exhaustive investigation of predicting binding modes for a range of systems using PELE (Protein Energy Landscape Exploration), an efficient and fast protein-ligand sampling algorithm. The systems analyzed (cytochrome P, kinase, protease, and nuclear hormone receptor) exhibit different complexities of ligand induced fit mechanisms and protein dynamics. The results are compared with results from classical molecular dynamics simulations and (induced fit) docking. This study shows that ligand induced side chain rearrangements and smaller to medium backbone movements are captured well in PELE. Large secondary structure rearrangements, however, remain challenging for all employed techniques. Relevant binding modes (ligand heavy atom RMSD < 1.0 Å) can be obtained by the PELE method within a few hours of simulation, positioning PELE as a tool applicable for rapid drug design cycles. PMID:26974351

  7. Informal Caregiver Characteristics Associated with Viral Load Suppression Among Current or Former Injection Drug Users Living with HIV/AIDS.

    PubMed

    Mitchell, Mary M; Robinson, Allysha C; Nguyen, Trang Q; Knowlton, Amy R

    2015-11-01

    Few studies have examined the association between having an informal (unpaid) caregiver and viral suppression among persons living with HIV/AIDS (PLHIV) who are on antiretroviral therapy. The current study examined relationships between caregivers' individual and social network characteristics and care recipient viral suppression. Baseline data were from the BEACON study caregivers and their HIV seropositive former or current drug using care recipients, of whom 89 % were African American (N = 258 dyads). Using adjusted logistic regression, care recipient's undetectable viral load was positively associated with caregiver's limited physical functioning and negatively associated with caregivers having few family members to turn to for problem solving, a greater number of current drug users in their network, and poorer perceptions of the care recipient's mental health. Results further understandings of interpersonal relationship factors important to PLHIV's health outcomes, and the need for caregiving relationship-focused intervention to promote viral suppression among PLHIV. PMID:25969180

  8. Informal Caregiver Characteristics Associated with Viral Load Suppression Among Current or Former Injection Drug Users Living with HIV/AIDS.

    PubMed

    Mitchell, Mary M; Robinson, Allysha C; Nguyen, Trang Q; Knowlton, Amy R

    2015-11-01

    Few studies have examined the association between having an informal (unpaid) caregiver and viral suppression among persons living with HIV/AIDS (PLHIV) who are on antiretroviral therapy. The current study examined relationships between caregivers' individual and social network characteristics and care recipient viral suppression. Baseline data were from the BEACON study caregivers and their HIV seropositive former or current drug using care recipients, of whom 89 % were African American (N = 258 dyads). Using adjusted logistic regression, care recipient's undetectable viral load was positively associated with caregiver's limited physical functioning and negatively associated with caregivers having few family members to turn to for problem solving, a greater number of current drug users in their network, and poorer perceptions of the care recipient's mental health. Results further understandings of interpersonal relationship factors important to PLHIV's health outcomes, and the need for caregiving relationship-focused intervention to promote viral suppression among PLHIV.

  9. Illicit Drug Use and the Social Context of HIV/AIDS in Alabama's Black Belt

    ERIC Educational Resources Information Center

    Lichtenstein, Bronwen

    2007-01-01

    Context: The rural Black Belt of Alabama is among the poorest areas of the nation. Poverty, lack of health infrastructure, and health disparities involving HIV/AIDS and other diseases reflect the lower life expectancy of people in the region. The Black Belt region has the highest HIV rates in rural America. Purpose: Using Alabama as a case…

  10. Hearing Aid

    MedlinePlus

    ... and Food and Drug Administration Staff FDA permits marketing of new laser-based hearing aid with potential ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  11. Evaluation of computer-aided design and drafting for the electric power industry. Final report

    SciTech Connect

    Anuskiewicz, T.; Barduhn, G.; Lowther, B.; Osman, I.

    1984-01-01

    This report reviews current and future computer-aided design and drafting (CADD) technology relative to utility needs and to identify useful development projects that may be undertaken by EPRI. The principal conclusions are that computer aids offer substantial cost and time savings and that computer systems are being developed to take advantage of the savings. Data bases are not available for direct communication between computers used by the power industry and will limit benefits to the industry. Recommendations are made for EPRI to take the initiative to develop the data bases for direct communication between power industry computers and to research, develop, and demonstrate new applications within the industry. Key components of a CADD system are described. The state of the art of two- and three-dimensional CADD systems to perform graphics and project management control functions are assessed. Comparison is made of three-dimensional electronic models and plastic models.

  12. Molecular docking and structure-based drug design strategies.

    PubMed

    Ferreira, Leonardo G; Dos Santos, Ricardo N; Oliva, Glaucius; Andricopulo, Adriano D

    2015-07-22

    Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.

  13. Structure and Ligand Based Drug Design Strategies in the Development of Novel 5-LOX Inhibitors

    PubMed Central

    Aparoy, Polamarasetty; Kumar Reddy, Kakularam; Reddanna, Pallu

    2012-01-01

    Lipoxygenases (LOXs) are non-heme iron containing dioxygenases involved in the oxygenation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA). Depending on the position of insertion of oxygen, LOXs are classified into 5-, 8-, 9-, 12- and 15-LOX. Among these, 5-LOX is the most predominant isoform associated with the formation of 5-hydroperoxyeicosatetraenoic acid (5-HpETE), the precursor of non-peptido (LTB4) and peptido (LTC4, LTD4, and LTE4) leukotrienes. LTs are involved in inflammatory and allergic diseases like asthma, ulcerative colitis, rhinitis and also in cancer. Consequently 5-LOX has become target for the development of therapeutic molecules for treatment of various inflammatory disorders. Zileuton is one such inhibitor of 5-LOX approved for the treatment of asthma. In the recent times, computer aided drug design (CADD) strategies have been applied successfully in drug development processes. A comprehensive review on structure based drug design strategies in the development of novel 5-LOX inhibitors is presented in this article. Since the crystal structure of 5-LOX has been recently solved, efforts to develop 5-LOX inhibitors have mostly relied on ligand based rational approaches. The present review provides a comprehensive survey on these strategies in the development of 5-LOX inhibitors. PMID:22680930

  14. 21 CFR 516.29 - Termination of MUMS-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  15. 21 CFR 516.29 - Termination of MUMS-drug designation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  16. 21 CFR 516.29 - Termination of MUMS-drug designation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  17. DeMAID: A Design Manager's Aide for Intelligent Decomposition user's guide

    NASA Technical Reports Server (NTRS)

    Rogers, James L.

    1989-01-01

    A design problem is viewed as a complex system divisible into modules. Before the design of a complex system can begin, the couplings among modules and the presence of iterative loops is determined. This is important because the design manager must know how to group the modules into subsystems and how to assign subsystems to design teams so that changes in one subsystem will have predictable effects on other subsystems. Determining these subsystems is not an easy, straightforward process and often important couplings are overlooked. Moreover, the planning task must be repeated as new information become available or as the design specifications change. The purpose of this research is to develop a knowledge-based tool called the Design Manager's Aide for Intelligent Decomposition (DeMAID) to act as an intelligent advisor for the design manager. DeMaid identifies the subsystems of a complex design problem, orders them into a well-structured format, and marks the couplings among the subsystems to facilitate the use of multilevel tools. DeMAID also provides the design manager with the capability of examining the trade-offs between sequential and parallel processing. This type of approach could lead to a substantial savings or organizing and displaying a complex problem as a sequence of subsystems easily divisible among design teams. This report serves as a User's Guide for the program.

  18. An evaluation of computer aided design of below-knee prosthetic sockets.

    PubMed

    Topper, A K; Fernie, G R

    1990-12-01

    Forty-eight below-knee amputees compared sockets designed using CANFIT computer aided design (CAD) software with sockets designed using conventional methods. Each subject was fitted by one prosthetist who used conventional techniques and one who used the CANFIT system to design the socket. Prosthetists alternated design methods for each new subject. The prosthetist using the conventional techniques was allowed up to 2 design attempts and the prosthetist using the CANFIT system was allowed up to 5 design attempts. After 2 design attempts with each method 21% of the subjects preferred the CANFIT design socket. Following up to 5 attempts 54% preferred the CANFIT designed socket. A jury of experts made an assessment of the CANFIT system and of CAD in prosthetics. The jury did not think that the version of the system tested was cost effective but that at the rate that it was improving it would become such within 3 to 5 years. The jury noted that, as well as monetary benefits, CAD presents the possibility of benefits in other areas such as research and teaching. A number of specific suggestions regarding the use and development of CAD in prosthetics were also made.

  19. Operator Station Design System - A computer aided design approach to work station layout

    NASA Technical Reports Server (NTRS)

    Lewis, J. L.

    1979-01-01

    The Operator Station Design System is resident in NASA's Johnson Space Center Spacecraft Design Division Performance Laboratory. It includes stand-alone minicomputer hardware and Panel Layout Automated Interactive Design and Crew Station Assessment of Reach software. The data base consists of the Shuttle Transportation System Orbiter Crew Compartment (in part), the Orbiter payload bay and remote manipulator (in part), and various anthropometric populations. The system is utilized to provide panel layouts, assess reach and vision, determine interference and fit problems early in the design phase, study design applications as a function of anthropometric and mission requirements, and to accomplish conceptual design to support advanced study efforts.

  20. Design-based approach to ethics in computer-aided diagnosis

    NASA Astrophysics Data System (ADS)

    Collmann, Jeff R.; Lin, Jyh-Shyan; Freedman, Matthew T.; Wu, Chris Y.; Hayes, Wendelin S.; Mun, Seong K.

    1996-04-01

    A design-based approach to ethical analysis examines how computer scientists, physicians and patients make and justify choices in designing, using and reacting to computer-aided diagnosis (CADx) systems. The basic hypothesis of this research is that values are embedded in CADx systems during all phases of their development, not just retrospectively imposed on them. This paper concentrates on the work of computer scientists and physicians as they attempt to resolve central technical questions in designing clinically functional CADx systems for lung cancer and breast cancer diagnosis. The work of Lo, Chan, Freedman, Lin, Wu and their colleagues provides the initial data on which this study is based. As these researchers seek to increase the rate of true positive classifications of detected abnormalities in chest radiographs and mammograms, they explore dimensions of the fundamental ethical principal of beneficence. The training of CADx systems demonstrates the key ethical dilemmas inherent in their current design.

  1. Computer-aided design of high-contact-ratio gears for minimum dynamic load and stress

    NASA Technical Reports Server (NTRS)

    Lin, Hsiang Hsi; Lee, Chinwai; Oswald, Fred B.; Townsend, Dennis P.

    1990-01-01

    A computer aided design procedure is presented for minimizing dynamic effects on high contact ratio gears by modification of the tooth profile. Both linear and parabolic tooth profile modifications of high contact ratio gears under various loading conditions are examined and compared. The effects of the total amount of modification and the length of the modification zone were systematically studied at various loads and speeds to find the optimum profile design for minimizing the dynamic load and the tooth bending stress. Parabolic profile modification is preferred over linear profile modification for high contact ratio gears because of its lower sensitivity to manufacturing errors. For parabolic modification, a greater amount of modification at the tooth tip and a longer modification zone are required. Design charts are presented for high contact ratio gears with various profile modifications operating under a range of loads. A procedure is illustrated for using the charts to find the optimum profile design.

  2. Pocket-based drug design: exploring pocket space.

    PubMed

    Zheng, Xiliang; Gan, Linfeng; Wang, Erkang; Wang, Jin

    2013-01-01

    The identification and application of druggable pockets of targets play a key role in in silico drug design, which is a fundamental step in structure-based drug design. Herein, some recent progresses and developments of the computational analysis of pockets have been covered. Also, the pockets at the protein-protein interfaces (PPI) have been considered to further explore the pocket space for drug discovery. We have presented two case studies targeting the kinetic pockets generated by normal mode analysis and molecular dynamics method, respectively, in which we focus upon incorporating the pocket flexibility into the two-dimensional virtual screening with both affinity and specificity. We applied the specificity and affinity (SPA) score to quantitatively estimate affinity and evaluate specificity using the intrinsic specificity ratio (ISR) as a quantitative criterion. In one of two cases, we also included some applications of pockets located at the dimer interfaces to emphasize the role of PPI in drug discovery. This review will attempt to summarize the current status of this pocket issue and will present some prospective avenues of further inquiry.

  3. Breaking the Glass Ceiling: Increasing the Meaningful Involvement of Women Living With HIV/AIDS (MIWA) in the Design and Delivery of HIV/AIDS Services.

    PubMed

    Carter, Allison; Greene, Saara; Nicholson, Valerie; O'Brien, Nadia; Sanchez, Margarite; de Pokomandy, Alexandra; Loutfy, Mona; Kaida, Angela

    2015-01-01

    The meaningful involvement of women living with HIV/AIDS (MIWA) is a key feature of women-centred HIV care, yet little is known about transforming MIWA from principle to practice. Drawing on focus group data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS), we explored HIV-positive women's meaningful involvement in the design and delivery of HIV/AIDS services in British Columbia, Canada. In this article, we highlight the benefits and tensions that emerge as women traverse multiple roles as service users and service providers within their care communities, and the impact this has on their access to care and overall health.

  4. Crew aiding and automation: A system concept for terminal area operations, and guidelines for automation design

    NASA Technical Reports Server (NTRS)

    Dwyer, John P.

    1994-01-01

    This research and development program comprised two efforts: the development of guidelines for the design of automated systems, with particular emphasis on automation design that takes advantage of contextual information, and the concept-level design of a crew aiding system, the Terminal Area Navigation Decision Aiding Mediator (TANDAM). This concept outlines a system capable of organizing navigation and communication information and assisting the crew in executing the operations required in descent and approach. In service of this endeavor, problem definition activities were conducted that identified terminal area navigation and operational familiarization exercises addressing the terminal area navigation problem. Both airborne and ground-based (ATC) elements of aircraft control were extensively researched. The TANDAM system concept was then specified, and the crew interface and associated systems described. Additionally, three descent and approach scenarios were devised in order to illustrate the principal functions of the TANDAM system concept in relation to the crew, the aircraft, and ATC. A plan for the evaluation of the TANDAM system was established. The guidelines were developed based on reviews of relevant literature, and on experience gained in the design effort.

  5. 77 FR 71600 - Medicare Program; Request for Information To Aid in the Design and Development of a Survey...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-03

    ... HUMAN SERVICES Centers for Medicare & Medicaid Services Medicare Program; Request for Information To Aid in the Design and Development of a Survey Regarding Patient Experiences With Emergency Department Care AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Request for...

  6. Semantic Web Ontology and Data Integration: a Case Study in Aiding Psychiatric Drug Repurposing

    PubMed Central

    Liang, Chen; Sun, Jingchun; Tao, Cui

    2016-01-01

    Despite ongoing progress towards treating mental illness, there remain significant difficulties in selecting probable candidate drugs from the existing database. We describe an ontology — oriented approach aims to represent the nexus between genes, drugs, phenotypes, symptoms, and diseases from multiple information sources. Along with this approach, we report a case study in which we attempted to explore the candidate drugs that effective for both bipolar disorder and epilepsy. We constructed an ontology that incorporates the knowledge between the two diseases and performed semantic reasoning task on the ontology. The reasoning results suggested 48 candidate drugs that hold promise for a further breakthrough. The evaluation was performed and demonstrated the validity of the proposed ontology. The overarching goal of this research is to build a framework of ontology — based data integration underpinning psychiatric drug repurposing. This approach prioritizes the candidate drugs that have potential associations among genes, phenotypes and symptoms, and thus facilitates the data integration and drug repurposing in psychiatric disorders. PMID:27570661

  7. Identification of levothyroxine antichagasic activity through computer-aided drug repurposing.

    PubMed

    Bellera, Carolina L; Balcazar, Darío E; Alberca, Lucas; Labriola, Carlos A; Talevi, Alan; Carrillo, Carolina

    2014-01-01

    Cruzipain (Cz) is the major cysteine protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. A conformation-independent classifier capable of identifying Cz inhibitors was derived from a 163-compound dataset and later applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 3 of which were acquired and tested on Cz and T. cruzi epimastigotes proliferation. Among them, levothyroxine, traditionally used in hormone replacement therapy in patients with hypothyroidism, showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite. PMID:24592161

  8. Identification of levothyroxine antichagasic activity through computer-aided drug repurposing.

    PubMed

    Bellera, Carolina L; Balcazar, Darío E; Alberca, Lucas; Labriola, Carlos A; Talevi, Alan; Carrillo, Carolina

    2014-01-01

    Cruzipain (Cz) is the major cysteine protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. A conformation-independent classifier capable of identifying Cz inhibitors was derived from a 163-compound dataset and later applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 3 of which were acquired and tested on Cz and T. cruzi epimastigotes proliferation. Among them, levothyroxine, traditionally used in hormone replacement therapy in patients with hypothyroidism, showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.

  9. Identification of Levothyroxine Antichagasic Activity through Computer-Aided Drug Repurposing

    PubMed Central

    Bellera, Carolina L.; Balcazar, Darío E.; Alberca, Lucas; Labriola, Carlos A.; Carrillo, Carolina

    2014-01-01

    Cruzipain (Cz) is the major cysteine protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. A conformation-independent classifier capable of identifying Cz inhibitors was derived from a 163-compound dataset and later applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 3 of which were acquired and tested on Cz and T. cruzi epimastigotes proliferation. Among them, levothyroxine, traditionally used in hormone replacement therapy in patients with hypothyroidism, showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite. PMID:24592161

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

    PubMed

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

    2015-01-01

    Fragment-based drug discovery (FBDD) has caused a revolution in the process of drug discovery and design, with many FBDD leads being developed into clinical trials or approved in the past few years. Compared with traditional high-throughput screening, it displays obvious advantages such as efficiently covering chemical space, achieving higher hit rates, and so forth. In this review, we focus on the most recent developments of FBDD for improving drug discovery, illustrating the process and the importance of FBDD. In particular, the computational strategies applied in the process of FBDD and molecular-docking programs are highlighted elaborately. In most cases, docking is used for predicting the ligand-receptor interaction modes and hit identification by structurebased virtual screening. The successful cases of typical significance and the hits identified most recently are discussed. PMID:25420726

  11. Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

    NASA Astrophysics Data System (ADS)

    Kurtoglu, Yunus Emre

    The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.

  12. Current progress in Structure-Based Rational Drug Design marks a new mindset in drug discovery

    PubMed Central

    Lounnas, Valère; Ritschel, Tina; Kelder, Jan; McGuire, Ross; Bywater, Robert P.; Foloppe, Nicolas

    2013-01-01

    The past decade has witnessed a paradigm shift in preclinical drug discovery with structure-based drug design (SBDD) making a comeback while high-throughput screening (HTS) methods have continued to generate disappointing results. There is a deficit of information between identified hits and the many criteria that must be fulfilled in parallel to convert them into preclinical candidates that have a real chance to become a drug. This gap can be bridged by investigating the interactions between the ligands and their receptors. Accurate calculations of the free energy of binding are still elusive; however progresses were made with respect to how one may deal with the versatile role of water. A corpus of knowledge combining X-ray structures, bioinformatics and molecular modeling techniques now allows drug designers to routinely produce receptor homology models of increasing quality. These models serve as a basis to establish and validate efficient rationales used to tailor and/or screen virtual libraries with enhanced chances of obtaining hits. Many case reports of successful SBDD show how synergy can be gained from the combined use of several techniques. The role of SBDD with respect to two different classes of widely investigated pharmaceutical targets: (a) protein kinases (PK) and (b) G-protein coupled receptors (GPCR) is discussed. Throughout these examples prototypical situations covering the current possibilities and limitations of SBDD are presented. PMID:24688704

  13. Lithium-ion batteries for hearing aid applications: I. Design and performance

    NASA Astrophysics Data System (ADS)

    Passerini, S.; Owens, B. B.; Coustier, F.

    Rechargeable batteries have been designed for powering hearing aid devices (HAD). The cells, based on the lithium-ion chemistry, were designed in a size that is compatible with the existing HAD. The 10 mA h batteries were tested to characterize the design and the electrochemical performance from the point of view of a typical HAD application. Results are presented for constant-current tests, first-cycle conditions, charge voltage cut-off, rate performance, and cycle life. The pulse capabilities and the preliminary safety tests of the batteries will be presented in a following report. The results of the lithium-ion HAD cells developed in this project are compared with other battery chemistries: lithium-alloy and nickel-metal hydride secondary batteries and Zn-air primary batteries.

  14. Computer aided design of digital controller for radial active magnetic bearings

    NASA Technical Reports Server (NTRS)

    Cai, Zhong; Shen, Zupei; Zhang, Zuming; Zhao, Hongbin

    1992-01-01

    A five degree of freedom Active Magnetic Bearing (AMB) system is developed which is controlled by digital controllers. The model of the radial AMB system is linearized and the state equation is derived. Based on the state variables feedback theory, digital controllers are designed. The performance of the controllers are evaluated according to experimental results. The Computer Aided Design (CAD) method is used to design controllers for magnetic bearings. The controllers are implemented with a digital signal processing (DSP) system. The control algorithms are realized with real-time programs. It is very easy to change the controller by changing or modifying the programs. In order to identify the dynamic parameters of the controlled magnetic system, a special experiment was carried out. Also, the online Recursive Least Squares (RLS) parameter identification method is studied. It can be realized with the digital controllers. Online parameter identification is essential for the realization of an adaptive controller.

  15. Computer aided design of digital controller for radial active magnetic bearings

    NASA Astrophysics Data System (ADS)

    Cai, Zhong; Shen, Zupei; Zhang, Zuming; Zhao, Hongbin

    1992-05-01

    A five degree of freedom Active Magnetic Bearing (AMB) system is developed which is controlled by digital controllers. The model of the radial AMB system is linearized and the state equation is derived. Based on the state variables feedback theory, digital controllers are designed. The performance of the controllers are evaluated according to experimental results. The Computer Aided Design (CAD) method is used to design controllers for magnetic bearings. The controllers are implemented with a digital signal processing (DSP) system. The control algorithms are realized with real-time programs. It is very easy to change the controller by changing or modifying the programs. In order to identify the dynamic parameters of the controlled magnetic system, a special experiment was carried out. Also, the online Recursive Least Squares (RLS) parameter identification method is studied. It can be realized with the digital controllers. Online parameter identification is essential for the realization of an adaptive controller.

  16. Large Advanced Space Systems (LASS) computer-aided design program additions

    NASA Technical Reports Server (NTRS)

    Farrell, C. E.

    1982-01-01

    The LSS preliminary and conceptual design requires extensive iteractive analysis because of the effects of structural, thermal, and control intercoupling. A computer aided design program that will permit integrating and interfacing of required large space system (LSS) analyses is discussed. The primary objective of this program is the implementation of modeling techniques and analysis algorithms that permit interactive design and tradeoff studies of LSS concepts. Eight software modules were added to the program. The existing rigid body controls module was modified to include solar pressure effects. The new model generator modules and appendage synthesizer module are integrated (interfaced) to permit interactive definition and generation of LSS concepts. The mass properties module permits interactive specification of discrete masses and their locations. The other modules permit interactive analysis of orbital transfer requirements, antenna primary beam n, and attitude control requirements.

  17. Computer aided process planning and die design in simulation environment in sheet metal forming

    NASA Astrophysics Data System (ADS)

    Tisza, Miklós; Lukács, Zsolt

    2013-12-01

    During the recent 10-15 years, Computer Aided Process Planning and Die Design evolved as one of the most important engineering tools in sheet metal forming, particularly in the automotive industry. This emerging role is strongly emphasized by the rapid development of Finite Element Modeling, as well. The purpose of this paper is to give a general overview about the recent achievements in this very important field of sheet metal forming and to introduce some special results in this development activity. Therefore, in this paper, an integrated process simulation and die design system developed at the University of Miskolc, Department of Mechanical Engineering will be analyzed. The proposed integrated solutions have great practical importance to improve the global competitiveness of sheet metal forming in the very important segment of industry. The concept described in this paper may have specific value both for process planning and die design engineers.

  18. [A computer-aided design assessment system for recovery life support technology options].

    PubMed

    Chen, J; Wang, F; Sun, J; Shang, C

    1997-04-01

    A specific computer-aided decision support system was designed and implemented for design computation and decision assessment of environmental control and life support system of manned space station. An advanced multiobjective decision methodology and a hierarchic structure model of assessment index of recovery life support system was developed. The program incorporates a database for each technology option, metabolic design loads associated with crew activity, mission model variables to accommodate evolving mission requirements, and algorithms to produce products criteria in order to provide recommendations relative to candidate technology selection and development. A specific structure was developed for the decision system which consists of a database, a methodology base and a model base as well as their management systems. Moreover, a centre control system with friendly user interface plays a very important role in the man-computer interaction.

  19. 21 CFR 516.36 - Insufficient quantities of MUMS-designated drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.36 Insufficient quantities...

  20. 21 CFR 516.36 - Insufficient quantities of MUMS-designated drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.36 Insufficient quantities...