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Sample records for aided drug designing

  1. Computer Aided Drug Design: Success and Limitations.

    PubMed

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

    2016-01-01

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

  2. Computer-Aided Drug Design Methods.

    PubMed

    Yu, Wenbo; MacKerell, Alexander D

    2017-01-01

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

  3. Computer-aided drug design at Boehringer Ingelheim

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  4. 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.

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

    PubMed

    Zeng, Huahui; Wu, Xiangxiang

    2016-10-04

    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.

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

    PubMed

    Moretti, Loris; Sartori, Luca

    2016-10-01

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

  7. 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.

  8. 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

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

    PubMed Central

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

    2016-01-01

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

  10. Flexibility analysis of biomacromolecules with application to computer-aided drug design.

    PubMed

    Fulle, Simone; Gohlke, Holger

    2012-01-01

    Flexibility characteristics of biomacromolecules can be efficiently determined down to the atomic level by a graph-theoretical technique as implemented in the FIRST (Floppy Inclusion and Rigid Substructure Topology) and ProFlex software packages. The method has been successfully applied to a series of protein and nucleic acid structures. Here, we describe practical guidelines for setting up and performing a flexibility analysis, discuss current bottlenecks of the approach, and provide sample applications as to how this technique can support computer-aided drug design approaches.

  11. Computer Aided Drug Design for Multi-Target Drug Design: SAR /QSAR, Molecular Docking and Pharmacophore Methods.

    PubMed

    Abdolmaleki, Azizeh; Ghasemi, Jahan B; Ghasemi, Fatemeh

    2017-01-01

    Multi-target drugs against particular multiple targets get better protection, resistance profiles and curative influence by cooperative rules of a key beneficial target with resistance behavior and compensatory elements. Computational techniques can assist us in the efforts to design novel drugs (ligands) with a preferred bioactivity outline and alternative bioactive molecules at an early stage. A number of in silico methods have been explored extensively in order to facilitate the investigation of individual target agents and to propose a selective drug. A different, progressively more significant field which is used to predict the bioactivity of chemical compounds is the data mining method. Some of the previously mentioned methods have been investigated for multi-target drug design (MTDD) to find drug leads interact simultaneously with multiple targets. Several cheminformatics methods and structure-based approaches try to extract information from units working cooperatively in a biomolecular system to fulfill their task. To dominate the difficulties of the experimental specification of ligand-target structures, rational methods, namely molecular docking, SAR and QSAR are vital substitutes to obtain knowledge for each structure in atomic insight. These procedures are logically successful for the prediction of binding affinity and have shown promising potential in facilitating MTDD. Here, we review some of the important features of the multi-target therapeutics discoveries using the computational approach, highlighting the SAR, QSAR, docking and pharmacophore methods to discover interactions between drug-target that could be leveraged for curative benefits. A summary of each, followed by examples of its applications in drug design has been provided. Computational efficiency of each method has been represented according to its main strengths and limitations.

  12. 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

  13. 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.

  14. State-of-the-art technology in modern computer-aided drug design.

    PubMed

    Dalkas, Georgios A; Vlachakis, Dimitrios; Tsagkrasoulis, Dimosthenis; Kastania, Anastasia; Kossida, Sophia

    2013-11-01

    The quest for small drug-like compounds that selectively inhibit the function of biological targets has always been a major focus in the pharmaceutical industry and in academia as well. High-throughput screening of compound libraries requires time, cost and resources. Therefore, the use of alternative methods is necessary for facilitating lead discovery. Computational techniques that dock small molecules into macromolecular targets and predict the affinity and activity of the small molecule are widely used in drug design and discovery, and have become an integral part of the industrial and academic research. In this review, we present an overview of some state-of-the-art technologies in modern drug design that have been developed for expediting the search for novel drug candidates.

  15. 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…

  16. Computer Aided Drug Design Studies in the Discovery of Secondary Metabolites Targeted Against Age-Related Neurodegenerative Diseases.

    PubMed

    Scotti, Luciana; Scotti, Marcus Tullius

    2015-01-01

    Secondary metabolites are plant products that occur usually in differentiated cells, generally not being necessary for the cells themselves, but likely useful for the plant as a whole. Neurodegeneration can be found in many different levels in the neurons, it always begins at the molecular level and progresses toward the systemic levels. Usually, alterations are observed such as decreasing cholinergic impulse, toxicity related to reactive oxygen species (ROS, inflammatory "amyloid plaque" related processes, catecholamine disequilibrium, etc. Computer aided drug design (CADD has become relevant in the drug discovery process; technological advances in the areas of molecular structure characterization, computational science, and molecular biology have contributed to the planning of new drugs against neurodegenerative diseases. This review discusses scientific CADD studies of the secondary metabolites. Flavonoids, alkaloids, and xanthone compounds have been studied by various researchers (as inhibitory ligands in molecular docking; mainly with three enzymes: acetylcholinesterase (AChE; EC 3.1.1.7, butyrylcholinesterase (BChE; EC 3.1.1.8, and monoamine oxidase (MAO; EC 1.4.3.4. In addition, we have applied ligand-based-virtual screening (using Random Forest, associated with structure-based- virtual screening (docking of a small dataset of 469 alkaloids of the Apocynaceae family from an in-house data bank to select structures with potential inhibitory activity against human AChE. This computer-aided drug design study selected certain alkaloids that might be useful in further studies for the treatment of neurological disorders such as Alzheimer's and Parkinson's disease.

  17. A New Era for Cancer Target Therapies: Applying Systems Biology and Computer-Aided Drug Design to Cancer Therapies.

    PubMed

    Wong, Yung-Hao; Chiu, Chia-Chiun; Lin, Chih-Lung; Chen, Ting-Shou; Jheng, Bo-Ren; Lee, Yu-Ching; Chen, Jeremy; Chen, Bor-Sen

    In recent years, many systems biology approaches have been used with various cancers. The materials described here can be used to build bases to discover novel cancer therapy targets in connection with computer-aided drug design (CADD). A deeper understanding of the mechanisms of cancer will provide more choices and correct strategies in the development of multiple target drug therapies, which is quite different from the traditional cancer single target therapy. Targeted therapy is one of the most powerful strategies against cancer and can also be applied to other diseases. Due to the large amount of progress in computer hardware and the theories of computational chemistry and physics, CADD has been the main strategy for developing novel drugs for cancer therapy. In contrast to traditional single target therapies, in this review we will emphasize the future direction of the field, i.e., multiple target therapies. Structure-based and ligand-based drug designs are the two main topics of CADD. The former needs both 3D protein structures and ligand structures, while the latter only needs ligand structures. Ordinarily it is estimated to take more than 14 years and 800 million dollars to develop a new drug. Many new CADD software programs and techniques have been developed in recent decades. We conclude with an example where we combined and applied systems biology and CADD to the core networks of four cancers and successfully developed a novel cocktail for drug therapy that treats multiple targets.

  18. 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.

  19. Immunophilins and HIV-1 V3 loop for structure-based anti-AIDS drug design.

    PubMed

    Andrianov, Alexander M

    2009-02-01

    The model of the structural complex of cyclophilin A (CycA) belonging to the immunophilins family with the HIV-MN gp120 V3 loop was generated, and the computer-aided design of the immunophilin-derived peptide able to mask the biologically crucial V3 segments was implemented. To this end, the following problems were solved: (i) the NMR-based conformational analysis of the HIV-MN V3 loop was put into effect, and its low energy structure fitting the input experimental observations was determined; (ii) molecular docking of this V3 structure with the X-ray conformation of CycA was carried out, and the energy refining the simulated structural complex was performed; (iii) the matrix of inter-atomic distances for the amino acids of the molecules forming part of the built over-molecular ensemble was computed, the types of interactions responsible for its stabilization were analyzed, and the CycA stretch, which accounts for the binding to V3, was identified; (iv) the most probable 3D structure for this stretch in the unbound state was predicted, and its collation with the X-ray structure for the corresponding site of CycA was performed; (v) the potential energy function and its constituents were studied for the structural complex generated by molecular docking of the V3 loop with the CycA peptide offering the virtual molecule that imitates the CycA segment, making a key contribution to the interactions of the native protein with the HIV-1 principal neutralizing determinant; (vi) as a result of the studies above, the designed molecule was shown to be capable of the efficacious blockading the functionally crucial V3 sites; and (vii) based on the joint analysis of the evidence obtained previously and in the present study, the composition of the peptide cocktail presenting the promising anti-AIDS pharmacological substance was developed. The molecules simulated here by molecular modeling methods may become the first representatives of a new class of the chemical compounds

  20. Drug use first aid

    MedlinePlus

    ... gait ( ataxia ) Sweating or extremely dry, hot skin Violent or aggressive behavior Death Drug withdrawal symptoms also ... own safety in danger. Some drugs can cause violent and unpredictable behavior. Call for medical help. Do ...

  1. Pharmacological Targeting of AMP-Activated Protein Kinase and Opportunities for Computer-Aided Drug Design.

    PubMed

    Miglianico, Marie; Nicolaes, Gerry A F; Neumann, Dietbert

    2016-04-14

    As a central regulator of metabolism, the AMP-activated protein kinase (AMPK) is an established therapeutic target for metabolic diseases. Beyond the metabolic area, the number of medical fields that involve AMPK grows continuously, expanding the potential applications for AMPK modulators. Even though indirect AMPK activators are used in the clinics for their beneficial metabolic outcome, the few described direct agonists all failed to reach the market to date, which leaves options open for novel targeting methods. As AMPK is not actually a single molecule and has different roles depending on its isoform composition, the opportunity for isoform-specific targeting has notably come forward, but the currently available modulators fall short of expectations. In this review, we argue that with the amount of available structural and ligand data, computer-based drug design offers a number of opportunities to undertake novel and isoform-specific targeting of AMPK.

  2. 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.

  3. 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

  4. Electronic aids to conceptual design

    NASA Technical Reports Server (NTRS)

    Bouchard, Eugene E.

    1990-01-01

    Presented in viewgraph form are techniques to improve the conceptual design of complex systems. The paper discusses theory of design, flexible software tools for computer aided design, and methods for enhancing communication among design teams.

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

    PubMed

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

    2011-12-01

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

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

    PubMed

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

    2010-02-01

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

  7. Arthritis Genetics Analysis Aids Drug Discovery

    MedlinePlus

    ... Matters NIH Research Matters January 13, 2014 Arthritis Genetics Analysis Aids Drug Discovery An international research team ... may play a role in triggering the disease. Genetic factors are also thought to play a role. ...

  8. Computer aided airship design

    NASA Technical Reports Server (NTRS)

    Davis, S. J.; Rosenstein, H.

    1975-01-01

    The Comprehensive Airship Sizing and Performance Computer Program (CASCOMP) is described which was developed and used in the design and evaluation of advanced lighter-than-air (LTA) craft. The program defines design details such as engine size and number, component weight buildups, required power, and the physical dimensions of airships which are designed to meet specified mission requirements. The program is used in a comparative parametric evaluation of six advanced lighter-than-air concepts. The results indicate that fully buoyant conventional airships have the lightest gross lift required when designed for speeds less than 100 knots and the partially buoyant concepts are superior above 100 knots. When compared on the basis of specific productivity, which is a measure of the direct operating cost, the partially buoyant lifting body/tilting prop-rotor concept is optimum.

  9. Detailed computational study of the active site of the hepatitis C viral RNA polymerase to aid novel drug design.

    PubMed

    Barakat, Khaled H; Law, John; Prunotto, Alessio; Magee, Wendy C; Evans, David H; Tyrrell, D Lorne; Tuszynski, Jack; Houghton, Michael

    2013-11-25

    The hepatitis C virus (HCV) RNA polymerase, NS5B, is a leading target for novel and selective HCV drug design. The enzyme has been the subject of intensive drug discovery aimed at developing direct acting antiviral (DAA) agents that inhibit its activity and hence prevent the virus from replicating its genome. In this study, we focus on one class of NS5B inhibitors, namely nucleos(t)ide mimetics. Forty-one distinct nucleotide structures have been modeled within the active site of NS5B for the six major HCV genotypes. Our comprehensive modeling protocol employed 287 different molecular dynamics simulations combined with the molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) methodology to rank and analyze these structures for all genotypes. The binding interactions of the individual compounds have been investigated and reduced to the atomic level. The present study significantly refines our understanding of the mode of action of NS5B-nucleotide-inhibitors, identifies the key structural elements necessary for their activity, and implements the tools for ranking the potential of additional much needed novel inhibitors of NS5B.

  10. 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.

  11. De novo computer-aided design of novel antiviral agents.

    PubMed

    Massarotti, Alberto; Coluccia, Antonio; Sorba, Giovanni; Silvestri, Romano; Brancale, Andrea

    2012-01-01

    Computer-aided drug design techniques have become an integral part of the drug discovery process. In particular, de novo methodologies can be useful to identify putative ligands for a specific target relying only on the structural information of the target itself. Here we discuss the basic de novo approaches available and their application in antiviral drug design.:

  12. 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.

  13. 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.

  14. Rational drug design.

    PubMed

    Mandal, Soma; Moudgil, Mee'nal; Mandal, Sanat K

    2009-12-25

    In this article, current knowledge of drug design is reviewed and an approach of rational drug design is presented. The process of drug development is challenging, expensive, and time consuming, although this process has been accelerated due to the development of computational tools and methodologies. The current target based drug design approach is incomplete because most of the drugs developed by structure guided approaches have been shown to have serious toxic side effects. Otherwise these drugs would have been an ideal choice for the treatment of diseases. Hence, rational drug design would require a multidisciplinary approach. In this regard, incorporation of gene expression technology and bioinformatics tools would be indispensable in the structure based drug design. Global gene expression data and analysis of such data using bioinformatics tools will have numerous benefits such as efficiency, cost effectiveness, time saving, and will provide strategies for combination therapy in addition to overcoming toxic side effects. As a result of incorporation of gene expression data, partial benefit of the structure based drug design is slowly emerging and rapidly changing the approach of the drug development process. To achieve the full benefit of developing a successful drug, multidisciplinary approaches (approaches such as computational chemistry and gene expression analysis, as discussed in this article) would be necessary. In the future, there is adequate room for the development of more sophisticated methodologies.

  15. 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.

  16. Computer-aided design of LSI topology

    NASA Astrophysics Data System (ADS)

    Seliutin, V. A.

    The problems and methods of the computer-aided design of the topology of LSI circuits and computer-aided manufacture of LSI templates are reviewed. Topics discussed include algorithms for the layout of cells and circuit units, algorithms for tracing connections, the design of the topology of matrix LSI, and the topology of functional LSI circuit units based on MIS structures. The discussion also covers the design of the layout of LSI circuits with single-layer commutation, application examples, and the main trends in the computer-aided design of LSI circuits.

  17. A computer-aided regulator design.

    NASA Technical Reports Server (NTRS)

    Karmarkar, J. S.; Siljak, D. D.

    1972-01-01

    A unified computer-aided method for the design of linear and nonlinear regulators is discussed. The general mathematical programming approach considered involves the determination of a vector that solves the problem of minimizing the objective function subject to constraints. Classical design problems stated are related to stability design, dominant mode design, and comprehensive design. A computer algorithm is also developed.

  18. 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)

  19. 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…

  20. Opioids and designer drugs.

    PubMed

    Ford, M; Hoffman, R S; Goldfrank, L R

    1990-08-01

    Despite the increasing use of other illicit drugs, opioid abuse, overdose, and the ensuing medical complications continue to pose management challenges for the emergency physician. Heroin use is increasing as abusers of cocaine seek a drug to prolong cocaine's effects while blunting the postcocaine depression. Clandestine chemists have created newer, more powerful compounds--designer drugs--whose potencies are many-fold that of the presently available opioids. Aggressive airway support and use of naloxone enable the emergency physician to salvage many of these patients, leaving the many medical complications of parenteral and inhalational use as the greatest management challenge.

  1. Computer Aided Control System Design (CACSD)

    NASA Technical Reports Server (NTRS)

    Stoner, Frank T.

    1993-01-01

    The design of modern aerospace systems relies on the efficient utilization of computational resources and the availability of computational tools to provide accurate system modeling. This research focuses on the development of a computer aided control system design application which provides a full range of stability analysis and control design capabilities for aerospace vehicles.

  2. [Designer drug induced psychosis].

    PubMed

    Fullajtar, Mate; Ferencz, Csaba

    2012-06-01

    3,4-methylene-dioxy-pyrovalerone (MDPV) is a popular designer drug in Hungary, known as MP4. We present a case of a 34-year-old man, whose first psychotic episode was observed in the presence of MP4 use. The paranoid ideas of reference and the dereistic thinking could be the consequence of drug-induced psychosis. Within 24 hours after the intoxication was over delirium set in. The patient's history included only the use of MP4, use of other kinds of drugs was negated. The drug tests were negative, amphetamine derivates were not detectable in the urine sample. It is most likely that the MP4 pill contained an amount of MDPV less than detectable. In conclusion we suggest that the clinical picture could be the consequence of regular MDPV use.

  3. 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.

  4. 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.

  5. Inhibitory effect of isothiocyanate derivant targeting AGPS by computer-aid drug design on proliferation of glioma and hepatic carcinoma cells.

    PubMed

    Zhu, Yu; Li, Wen-Ming; Zhang, Ling; Xue, Jing; Zhao, Meng; Yang, Ping

    2015-01-01

    Lipids metabolism was involved in the process of many types of tumor and alkylglycerone phosphate synthase (AGPS) was considered implicated in tumor process. Benzyl isothiocyanate (BITC) showed the inhibitory effect of tumor and AGPS activity, therefore, we screened a group of small molecular compound based on BITC by computer-aid design targeting AGPS and the results showed that the derivants could suppress the proliferation, the expression of tumor related genes such as survivin and Bcl-2, and the level of ether lipids such as lysophosphatidic acid ether (LPAe) and platelet activating factor ether (PAFe); however, the activity of caspase-3/8 was improved in glioma U87MG and hepatic carcinoma HepG2 cells in vitro.

  6. 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.

  7. Injection drug use and HIV/AIDS transmission in China.

    PubMed

    Chu, Tian Xin; Levy, Judith A

    2005-01-01

    After nearly three decades of being virtually drug free, use of heroin and other illicit drugs has re-emerged in China as a major public health problem. One result is that drug abuse, particularly heroin injection, has come to play a predominant role in fueling China's AIDS epidemic. The first outbreak of HIV among China's IDUs was reported in the border area of Yunnan province between China and Myanmar where drug trafficking is heavy. Since then drug-related HIV has spread to all 31 provinces, autonomous regions and municipalities. This paper provides an overview to HIV/AIDS transmission through injection drug use in China. It begins with a brief history of the illicit drug trade in China, followed by a discussion of the emergence of drug related AIDS, and a profile of drug users and their sexual partners who have contracted the virus or who are vulnerable to infection. It ends by summarizing three national strategies being used by China to address both drug use and AIDS as major health threats.

  8. 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.

  9. Designing Visual Aids That Promote Risk Literacy.

    PubMed

    Garcia-Retamero, Rocio; Cokely, Edward T

    2017-02-01

    Background Effective risk communication is essential for informed decision making. Unfortunately, many people struggle to understand typical risk communications because they lack essential decision-making skills. Objective The aim of this study was to review the literature on the effect of numeracy on risk literacy, decision making, and health outcomes, and to evaluate the benefits of visual aids in risk communication. Method We present a conceptual framework describing the influence of numeracy on risk literacy, decision making, and health outcomes, followed by a systematic review of the benefits of visual aids in risk communication for people with different levels of numeracy and graph literacy. The systematic review covers scientific research published between January 1995 and April 2016, drawn from the following databases: Web of Science, PubMed, PsycINFO, ERIC, Medline, and Google Scholar. Inclusion criteria were investigation of the effect of numeracy and/or graph literacy, and investigation of the effect of visual aids or comparison of their effect with that of numerical information. Thirty-six publications met the criteria, providing data on 27,885 diverse participants from 60 countries. Results Transparent visual aids robustly improved risk understanding in diverse individuals by encouraging thorough deliberation, enhancing cognitive self-assessment, and reducing conceptual biases in memory. Improvements in risk understanding consistently produced beneficial changes in attitudes, behavioral intentions, trust, and healthy behaviors. Visual aids were found to be particularly beneficial for vulnerable and less skilled individuals. Conclusion Well-designed visual aids tend to be highly effective tools for improving informed decision making among diverse decision makers. We identify five categories of practical, evidence-based guidelines for heuristic evaluation and design of effective visual aids.

  10. 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…

  11. 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…

  12. 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.

  13. Shape Signatures: speeding up computer aided drug discovery.

    PubMed

    Meek, Peter J; Liu, ZhiWei; Tian, LiFeng; Wang, Ching Y; Welsh, William J; Zauhar, Randy J

    2006-10-01

    Identifying potential lead molecules is becoming a more automated process. We review Shape Signatures, a tool that is effective and easy to use compared with most computer aided drug design techniques. Laboratory researchers can apply this in silico technique cost-effectively without the need for specialized computer backgrounds. Identifying a potential lead molecule requires database screening, and this becomes rate-limiting once the database becomes too large. The use of Shape Signatures eliminates this concern and offers molecule screening rates that are in advance of any currently available method. Shape Signatures provides a conduit for researchers to conduct rapid identification of potential active molecules, and studies with this tool can be initiated with only one bioactive lead or receptor site.

  14. 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.

  15. 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...

  16. 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...

  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, 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...

  19. 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...

  20. 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.

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. Current status of drug use and HIV/AIDS prevention in drug users in China

    PubMed Central

    Li, Jianhua; Li, Xinyue

    2014-01-01

    The objective of this paper is to review the current status of drug use and HIV/AIDS prevention for drug users in China and provide scientific evidence for HIV/AIDS prevention and control in drug users. Literature and articles related to drug abuse in China, as well as the results of prevention efforts and successful cases regarding HIV/AIDS prevention in drug users, are reviewed. Lessons learned are drawn out for the future improvement of work and the sustainable development of treatment programs. The number of drug users in China is increasing. Even though the number of opioid-type drug users is growing more slowly than in the past, the number of amphetamine-type stimulant users has increased sharply. It has been proven that methadone maintenance treatment and syringe exchange programs gradually and successfully control HIV/AIDS transmission in drug users. However, it is necessary to enhance these prevention methods and expand their coverage. In addition, the strengthening of antiretroviral therapy (ART) treatment for HIV-infected drug users is crucial for HIV/AIDS prevention and control. The rapidly growing number of amphetamine-type stimulant users, along with their high-risk behavior, poses a hidden danger of greater HIV/AIDS transmission through sexual intercourse in the near future. PMID:25284965

  7. Market power and state costs of HIV/AIDS drugs.

    PubMed

    Leibowitz, Arleen A; Sood, Neeraj

    2007-03-01

    We examine whether U.S. states can use their market power to reduce the costs of supplying prescription drugs to uninsured and underinsured persons with HIV through a public program, the AIDS Drug Assistance Program (ADAP). Among states that purchase drugs from manufacturers and distribute them directly to clients, those that purchase a greater volume pay lower average costs per prescription. Among states depending on retail pharmacies to distribute drugs and then claiming rebates from manufacturers, those that contract with smaller numbers of pharmacy networks have lower average costs. Average costs per prescription do not differ between the two purchase methods.

  8. 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.

  9. CAD/CAM (Computer-Aided Design/Computer-Aided Manufacturing) Highlights.

    DTIC Science & Technology

    1984-10-01

    AD-Aift 532 CAD/CAN (COMPUTER-AIDED DESIGN /COMPUTER-ADD D7 MANUFACTURING) HIGHLIGHTSMU ARMY INDUSTRIAL BASE ENGINEERING ACTIVITY ROCK ISLAND IL D L...1985 B DISCLAIMER This document presents information for the US Army Materiel Command (AMC) Computer-Alded Design /Computer-Aided Manufacturing...contains summaries of Army Computer-Aided Design (CAD) and . Computer-Aided Manufacturing (CAM) efforts that are either completed or ongoing. The Army CAD

  10. 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.

  11. 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.

  12. Drug use and HIV/AIDS in China.

    PubMed

    Liu, Zhimin; Lian, Zhi; Zhao, Chengzheng

    2006-03-01

    This paper on drug use and HIV/AIDS in China follows on from the column's May 2005 article on the description of the first methadone maintenance clinic in Beijing. Methadone maintenance clinics and needle exchange programmes are now being implemented in China as a response to the rapid increase in prevalence of HIV/AIDS over the last 10-15 years. It is worth noting that in prior years methadone was available only as for short-term detoxification from opioids and for research purposes. Accordingly, the Department of Health Education and Behavioural Intervention at the National Center for AIDS Prevention and Control in China plans to establish 1,000 methadone replacement clinics within the next 5 years to treat 200,000 heroin-dependent users who are at increased risk of HIV/AIDS. Robert Ali & Rachel HumeniukEditors, Asia Pacific ColumnThe cumulative number of registered drug users in mainland China increased from 70,000 in 1990 to 1.14 million in 2004. Heroin continues to be the most commonly used drug in China; however, polydrug use is popular among heroin users. Sedatives/hypnotics (e.g. triazolam) and other uncontrolled prescription opioids (e.g. pethidine and tramadol) are used commonly in combination with heroin. The majority of drug users (79%) are young people aged between 17 and 35 years and comprise predominantly farmers (30%) and unemployed people (45%). The HIV/AIDS epidemic in China has reached expansion phase (1995-present). It is estimated that the actual number of HIV/AIDS cases reached 840,000, including 80,000 actual AIDS patients, in 2003, with injecting drug users (IDUs) making up the largest proportion of these cases. Although the prevalence rate of HIV/AIDS is only 0.065% in the Chinese population overall, there is potential for an explosive spread of HIV/AIDS if preventative measures are not employed. Supported by the Chinese government and other related international organisations, harm reduction strategies such as methadone maintenance

  13. 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.

  14. 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.

  15. 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

  16. Protein Structure Network-based Drug Design.

    PubMed

    Liang, Zhongjie; Hu, Guang

    2016-01-01

    Although structure-based drug design (SBDD) has become an indispensable tool in drug discovery for a long time, it continues to pose major challenges to date. With the advancement of "omics" techniques, systems biology has enriched SBDD into a new era, called polypharmacology, in which multi-targets drug or drug combination is designed to fight complex diseases. As a preliminary tool in systems biology, protein structure networks (PSNs) treat a protein as a set of residues linked by edges corresponding to the intramolecular interactions existing in folded structures between the residues. The PSN offers a computationally efficient tool to study the structure and function of proteins, and thus may facilitate structurebased drug design. Herein, we provide an overview of recent advances in PSNs, from predicting functionally important residues, to charactering protein-protein interactions and allosteric communication paths. Furthermore, we discuss potential pharmacological applications of PSN concepts and tools, and highlight the application to two families of drug targets, GPCRs and Hsp90. Although the application of PSNs as a framework for computer-aided drug discovery has been limited to date, we put forward the potential utility value in the near future and propose the PSNs could also serve as a new tool for polypharmacology research.

  17. 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.”...

  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, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 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. 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

  1. [AIDS epidemiology and prevention in i.v. drug addicts].

    PubMed

    Uchtenhagen, A

    1988-01-01

    The incidence of AIDS cases in intravenous drug abusers is growing faster than in other risk groups, in Switzerland as well as in Europe in general. By end of May 1988, 27% of all AIDS cases registered nationally were injecting drugs. The prevalence of HIV antibodies is known from selected samples only, on the basis of voluntary testing. In 1986, among all intravenous drug users in residential treatment nation-wide, 90% were tested and thereof 55% seropositive. In a sample of drug abusers in out-patient treatment in Zurich in 1987, seropositivity was documented for 42% of male and 63% of female patients. According to registered AIDS cases, there is no differential risk for both sexes. Duration of intravenous drug abuse is the only relevant risk factor so far. Preventive change in risk taking behaviour is a minimalization of utilizing contaminated syringes/needles and a minimalization of unprotected sex (safer sex by regular use of condoms). An analysis of published data demonstrates that dissemination of information and availability of syringes/condoms are a pre-requisite for behaviour change, but by no means sufficient in order to elicit behaviour change. Drug abusers engaged in out-patient/residential treatment are available in high proportions for voluntary testing and for the intended behavioural changes. It is therefore of primary preventive interest to engage as many intravenous drug abusers as possible in treatment. Apart from drug-free residential treatment, out-patient treatment using Methadone provides positive results, whereas compulsory measures are considered to be of doubtful value.

  2. Structure aided design of chimeric antibiotics.

    PubMed

    Karoli, Tomislav; Mamidyala, Sreeman K; Zuegg, Johannes; Fry, Scott R; Tee, Ernest H L; Bradford, Tanya A; Madala, Praveen K; Huang, Johnny X; Ramu, Soumya; Butler, Mark S; Cooper, Matthew A

    2012-04-01

    The rise of antibiotic resistance is of great clinical concern. One approach to reducing the development of resistance is to co-administer two or more antibiotics with different modes of action. However, it can be difficult to control the distribution and pharmacokinetics of two drugs to ensure both concentrations remain within the range of therapeutic efficacy whilst avoiding adverse effects. Hybrid drugs, where two drugs are linked together with a flexible linker, have been explored, but the resultant large, flexible molecules can have poor bioavailability. We have developed a chimeric approach using click chemistry where the pharmacophores of two drugs are overlapped into a single smaller, more drug-like molecule. Design and selection of compounds were assisted by in silico structural docking. We prepared a series of compounds that include candidates showing activity against the targets of both trimethoprim; dihydrofolate reductase, and ciprofloxacin; DNA gyrase and topoisomerase IV. The resultant triazole containing molecules show modest, but broad spectrum activities against drug sensitive and resistant Gram-negative and Gram-positive bacteria, with no observable cytotoxicity.

  3. 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.

  4. Stigma, sexual risks, and the war on drugs: Examining drug policy and HIV/AIDS inequities among African Americans using the Drug War HIV/AIDS Inequities Model.

    PubMed

    Kerr, Jelani; Jackson, Trinidad

    2016-11-01

    The relationship between drug policy and HIV vulnerability is well documented. However, little research examines the links between racial/ethnic HIV disparities via the Drug War, sexual risk, and stigma. The Drug War HIV/AIDS Inequities Model has been developed to address this dearth. This model contends that inequitable policing and sentencing promotes sexual risks, resource deprivation, and ultimately greater HIV risk for African-Americans. The Drug War also socially marginalizes African Americans and compounds stigma for incarcerated and formerly incarcerated persons living with HIV/AIDS. This marginalization has implications for sexual risk-taking, access to health-promoting resources, and continuum of care participation. The Drug War HIV/AIDS Inequities Model may help illuminate mechanisms that promote increased HIV vulnerability as well as inform structural intervention development and targeting to address racial/ethnic disparities.

  5. 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.

  6. Computer-Aided Socket Design For Amputees

    NASA Astrophysics Data System (ADS)

    Novicov, Aleksey; Foort, James

    1983-07-01

    The fitting of sockets and artificial legs to amputees' stumps is a difficult and lengthy process that can take numerous trials. It has been proposed that most amputees can be fitted with a standard socket shape with minimal changes to the socket. To perform this task, a procedure is being developed at the Medical Engineering Resource Unit for computer aided socket design for amputees. An interactive PASCAL program, operating on a microcomputer, will prompt the operator (or prosthetist) by asking him to determine the condition of the stump. While the operator is inputing this information into the computer, together with a few critical anatomical measurements, a standard socket shape, viewed on the video monitor, will begin to change. Throughout the "shape fitting" procedure, the operator will have the ability to modify the socket shape on the screen with the use of a light pen. It will also be possible to view various cross-sections and different perspectives. The shape fitting procedure continues until a suitable socket shape is designed. Future efforts will focus on transferring the computer designed socket into a physical socket. The overall goal is to provide amputees with a better fit in less time and to objectify socket fitting so that new prosthetists may be easily taught.

  7. New drug treatments for HIV infection and AIDS. A review following the Seventh International Conference on AIDS, Florence 16-21 June 1991.

    PubMed

    Venning, G R; Scott, G M

    1992-03-01

    1. OBJECTIVE--To evaluate the status of clinical development of zidovudine and new drugs for the treatment of Human Immunodeficiency Virus (HIV) infections. 2. METHOD--A critical review of the clinical trial reports and assessment of the design and methodology of the therapeutic trials. Evaluation of the drugs being tested and of the specific difficulties in testing drugs in AIDS. 3. CONCLUSIONS--Drugs are being tested in a unique climate of public opinion characterised by (1) fast track criteria for regulatory approval (2) parallel track (compassionate release) of new drugs before adequate determination of safety and efficacy (3) resistance to the use of placebos in controlled trials.

  8. 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.

  9. 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,…

  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. [Drugs, health policy and AIDS: changes in a dependent policy].

    PubMed

    Loyola, Maria Andréa

    2008-04-01

    Since the 1970s the Brazilian government has made efforts to implement a pharmaceutical policy that, in spite of a market predominantly oligopolized and dominated by multinational pharmaceutical industries, guarantees access to essential drugs for the population. In this context, in 1999, a law regarding generics was approved. This article aims at analyzing the elements that interfered in the implementation process of this law. Based on specialized bibliography, on the debate in the Brazilian press (1992-2002) and on interviews with industry members, physicians, politicians, activists and civil servants we try to show that the implementation of generics in Brazil is strongly related to the AIDS epidemic. More precisely, it is related to the successful health policy against this disease involving different actors and a variety of elements to be analyzed here, among them the policy of copycat versions of drugs, the law of universal access to anti-AIDS drugs, the struggle of organized social movements, the governmental bureaucracy implemented for fighting this epidemic and the strong mobilization of the media.

  12. 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.

  13. The relationship between rational drug design and drug side effects.

    PubMed

    Wang, Juan; Li, Zhi-xin; Qiu, Cheng-xiang; Wang, Dong; Cui, Qing-hua

    2012-05-01

    Previous analysis of systems pharmacology has revealed a tendency of rational drug design in the pharmaceutical industry. The targets of new drugs tend to be close with the corresponding disease genes in the biological networks. However, it remains unclear whether the rational drug design introduces disadvantages, i.e. side effects. Therefore, it is important to dissect the relationship between rational drug design and drug side effects. Based on a recently released drug side effect database, SIDER, here we analyzed the relationship between drug side effects and the rational drug design. We revealed that the incidence drug side effect is significantly associated with the network distance of drug targets and diseases genes. Drugs with the distances of three or four have the smallest incidence of side effects, whereas drugs with the distances of more than four or smaller than three show significantly greater incidence of side effects. Furthermore, protein drugs and small molecule drugs show significant differences. Drugs hitting membrane targets and drugs hitting cytoplasm targets also show differences. Failure drugs because of severe side effects show smaller network distances than approved drugs. These results suggest that researchers should be prudent on rationalizing the drug design. Too small distances between drug targets and diseases genes may not always be advantageous for rational design for drug discovery.

  14. Computer-Aided Drug-Discovery Techniques that Account for Receptor Flexibility

    PubMed Central

    Durrant, Jacob D.; McCammon, J. Andrew

    2010-01-01

    Protein flexibility plays a critical role in ligand binding to both orthosteric and allosteric sites. We here review some of the computer-aided drug-design techniques currently used to account for protein flexibility, ranging from methods that probe local receptor flexibility in the region of the protein immediately adjacent to the binding site, to those that account for general flexibility in all protein regions. PMID:20888294

  15. Computer-aided drug-discovery techniques that account for receptor flexibility.

    PubMed

    Durrant, Jacob D; McCammon, J Andrew

    2010-12-01

    Protein flexibility plays a critical role in ligand binding to both orthosteric and allosteric sites. We here review some of the computer-aided drug-design techniques currently used to account for protein flexibility, ranging from methods that probe local receptor flexibility in the region of the protein immediately adjacent to the binding site, to those that account for general flexibility in all protein regions.

  16. A computer-aided drug discovery system for chemistry teaching.

    PubMed

    Gledhill, Robert; Kent, Sarah; Hudson, Brian; Richards, W Graham; Essex, Jonathan W; Frey, Jeremy G

    2006-01-01

    The Schools Malaria Project (http://emalaria.soton.ac.uk/) brings together school students with university researchers in the hunt for a new antimalaria drug. The design challenge being offered to students is to use a distributed drug search and selection system to design potential antimalaria drugs. The system is accessed via a Web interface. This e-science project displays the results of the trials in an accessible manner, giving students an opportunity for discussion and debate both with peers and with the university contacts. The project has been implemented by using distributed computing techniques, spreading computer load over a network of machines that cross institutional boundaries, forming a grid. This provides access to greater computing power and allows a much more complex and detailed formulation of the drug design problem to be tackled for research, teaching, and learning.

  17. 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.

  18. 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.

  19. 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.

  20. Computer-aided drug discovery research at a global contract research organization

    NASA Astrophysics Data System (ADS)

    Kitchen, Douglas B.

    2016-11-01

    Computer-aided drug discovery started at Albany Molecular Research, Inc in 1997. Over nearly 20 years the role of cheminformatics and computational chemistry has grown throughout the pharmaceutical industry and at AMRI. This paper will describe the infrastructure and roles of CADD throughout drug discovery and some of the lessons learned regarding the success of several methods. Various contributions provided by computational chemistry and cheminformatics in chemical library design, hit triage, hit-to-lead and lead optimization are discussed. Some frequently used computational chemistry techniques are described. The ways in which they may contribute to discovery projects are presented based on a few examples from recent publications.

  1. Computer-aided drug discovery research at a global contract research organization.

    PubMed

    Kitchen, Douglas B

    2016-11-01

    Computer-aided drug discovery started at Albany Molecular Research, Inc in 1997. Over nearly 20 years the role of cheminformatics and computational chemistry has grown throughout the pharmaceutical industry and at AMRI. This paper will describe the infrastructure and roles of CADD throughout drug discovery and some of the lessons learned regarding the success of several methods. Various contributions provided by computational chemistry and cheminformatics in chemical library design, hit triage, hit-to-lead and lead optimization are discussed. Some frequently used computational chemistry techniques are described. The ways in which they may contribute to discovery projects are presented based on a few examples from recent publications.

  2. Boron-Based Drug Design.

    PubMed

    Ban, Hyun Seung; Nakamura, Hiroyuki

    2015-06-01

    The use of the element boron, which is not generally observed in a living body, possesses a high potential for the discovery of new biological activity in pharmaceutical drug design. In this account, we describe our recent developments in boron-based drug design, including boronic acid containing protein tyrosine kinase inhibitors, proteasome inhibitors, and tubulin polymerization inhibitors, and ortho-carborane-containing proteasome activators, hypoxia-inducible factor 1 inhibitors, and topoisomerase inhibitors. Furthermore, we applied a closo-dodecaborate as a water-soluble moiety as well as a boron-10 source for the design of boron carriers in boron neutron capture therapy, such as boronated porphyrins and boron lipids for a liposomal boron delivery system.

  3. 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

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

    PubMed

    Singla, Rajeev K

    2015-01-01

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

  7. 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.

  8. 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).

  9. 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.

  10. Computer aids for integrated circuit design at Sandia National Laboratories

    NASA Astrophysics Data System (ADS)

    Brown, G. W.

    A general framework for a hierarchical computer-aided design (CAD) system for VLSI design is described. The system supports both functional and physical design in the area of initial design specification, system synthesis, simulation, mask layout, verification, and documentation. The system is being implemented in phases within a user environment on a DECsystem 20-VAX 11/780 computer network. It supports evolutionary changes as new technologies, design strategies, and application programs are developed.

  11. 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

    NASA Astrophysics Data System (ADS)

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

  12. Geometric modeling for computer aided design

    NASA Technical Reports Server (NTRS)

    Schwing, James L.

    1988-01-01

    Research focused on two major areas. The first effort addressed the design and implementation of a technique that allows for the visualization of the real time variation of physical properties. The second effort focused on the design and implementation of an on-line help system with components designed for both authors and users of help information.

  13. 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

  14. 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.

  15. Virtual Design of Chemical Penetration Enhancers for Transdermal Drug Delivery

    PubMed Central

    Golla, Sharath; Neely, Brian J.; Whitebay, Eric; Madihally, Sundar; Robinson, Robert L.; Gasem, Khaled A. M.

    2012-01-01

    Traditional drug design is a laborious and expensive process that often challenges the pharmaceutical industries. As a result, researchers have turned to computational methods for computer-assisted molecular design. Recently, genetic and evolutionary algorithms have emerged as efficient methods in solving combinatorial problems associated with computer-aided molecular design. Further, combining genetic algorithms (GAs) with quantitative structure-property relationship (QSPR) analyses has proved effective in drug design. In this work, we have integrated a new genetic algorithm and non-linear QSPR models to develop a reliable virtual screening algorithm for generation of potential chemical penetration enhancers (CPEs). The GA-QSPR algorithm has been implemented successfully to identify potential CPEs for transdermal drug delivery of insulin. Validation of the newly-identified CPE molecular structures was conducted through carefully designed experiments, which elucidated the cytotoxicity and permeability of the CPEs. PMID:22172168

  16. Virtual design of chemical penetration enhancers for transdermal drug delivery.

    PubMed

    Golla, Sharath; Neely, Brian J; Whitebay, Eric; Madihally, Sundar; Robinson, Robert L; Gasem, Khaled A M

    2012-04-01

    Traditional drug design is a laborious and expensive process that often challenges the pharmaceutical industries. As a result, researchers have turned to computational methods for computer-assisted molecular design. Recently, genetic and evolutionary algorithms have emerged as efficient methods in solving combinatorial problems associated with computer-aided molecular design. Further, combining genetic algorithms with quantitative structure-property relationship analyses has proved effective in drug design. In this work, we have integrated a new genetic algorithm and nonlinear quantitative structure-property relationship models to develop a reliable virtual screening algorithm for the generation of potential chemical penetration enhancers. The genetic algorithms-quantitative structure-property relationship algorithm has been implemented successfully to identify potential chemical penetration enhancers for transdermal drug delivery of insulin. Validation of the newly identified chemical penetration enhancer molecular structures was conducted through carefully designed experiments, which elucidated the cytotoxicity and permeability of the chemical penetration enhancers.

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

    PubMed

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

    2016-11-12

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

  18. 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.

  19. Computer Program Aids Design Of Impeller Blades

    NASA Technical Reports Server (NTRS)

    Chen, Wei-Chung; Galazin, John V.

    1992-01-01

    Impeller blades for centrifugal turbopumps designed quickly with help of computer program. Generates blade contours and continually subjects them to evaluation. Checks physical parameters to ensure they are compatible with required performance and recycles design if criteria not met. Program written for centrifugal turbomachinery, also adapted to such axial pump components as inducer blades and stator vanes.

  20. Space systems computer-aided design technology

    NASA Technical Reports Server (NTRS)

    Garrett, L. B.

    1984-01-01

    The interactive Design and Evaluation of Advanced Spacecraft (IDEAS) system is described, together with planned capability increases in the IDEAS system. The system's disciplines consist of interactive graphics and interactive computing. A single user at an interactive terminal can create, design, analyze, and conduct parametric studies of earth-orbiting satellites, which represents a timely and cost-effective method during the conceptual design phase where various missions and spacecraft options require evaluation. Spacecraft concepts evaluated include microwave radiometer satellites, communication satellite systems, solar-powered lasers, power platforms, and orbiting space stations.

  1. Microcomputer-Aided Control Systems Design.

    ERIC Educational Resources Information Center

    Roat, S. D.; Melsheimer, S. S.

    1987-01-01

    Describes a single input/single output feedback control system design program for IBM PC and compatible microcomputers. Uses a heat exchanger temperature control loop to illustrate the various applications of the program. (ML)

  2. 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.

  3. On computer-aided design of aerospace vehicles

    NASA Technical Reports Server (NTRS)

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

    1974-01-01

    Digital computers are being used in many engineering activities to support design work. This paper provides an overview of some of this work as it relates to the design of aerospace vehicles. Discussions are given of some of the complexities of the design process which lead to large design costs and time. A number of important but disjointed computer capabilities have evolved over the years in analysis, optimization, and graphics, and such capabilities aid in addressing the problem of design complexity. Examples of existing computer-aided design (CAD) systems are given and trends for future CAD systems are indicated, as well as their relationship to pertinent data management technology. It is suggested that major gains in design capability will occur through continued development of CAD methodology and that these gains may be accelerated through a large focused effort.

  4. Design of Training Aids and Devices.

    ERIC Educational Resources Information Center

    Lumsdaine, Arthur A.

    Training devices should be designed to provide efficient learning conditions, especially guided practice and prompt feedback. These devices can be more useful than their operational equipment counterparts because they facilitate the focusing of learner attention on particular components of a total operation, they make operations visible for study,…

  5. An Elective Course on Computer-Aided Process Design.

    ERIC Educational Resources Information Center

    Sommerfeld, Jude T.

    1979-01-01

    Describes an undergraduate chemical engineering course which has been offered at the Georgia Institute of Technology. The objectives, structure, instructional materials and content of this course, which emphasizes the structure and usage of computer-aided design systems, are also included. (HM)

  6. Competing Ideologies in Software Design for Computer-Aided Composition.

    ERIC Educational Resources Information Center

    LeBlanc, Paul

    1990-01-01

    Illustrates the ideological foundations of computer-assisted composition (CAC) software by comparing two computer-writing aids: "Grammatik II" and "Interchange." Notes that many of the best CAC programs have come out of the composition classroom. Argues that English departments must support and reward those who work in CAC design. (RS)

  7. The Journal of Computer- Aided Molecular Design: a bibliometric note

    NASA Astrophysics Data System (ADS)

    Willett, Peter

    2012-01-01

    Summarizes the articles in, and the citations to, volumes 2-24 of the Journal of Computer- Aided Molecular Design. The citations to the journal come from almost 2000 different sources that span a very wide range of academic subjects, with the most heavily cited articles being descriptions of software systems and of computational methods.

  8. 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.

  9. Robot-aided rehabilitation task design for inner shoulder muscles.

    PubMed

    Pei, Y; Kim, Y; Obinata, G; Genda, E; Stefanov, D

    2012-01-01

    In this paper, we propose a simultaneous design method of motion and external force trajectories for shoulder inner muscles in the robot-aided rehabilitation system, based on a biomechanical analysis of patient's body. The rehabilitation efficiency evaluation function was maximized by Genetic Algorithm (GA), where the structure of spline curves parameters are pre-defined, and the structural parameters are explored to design smooth rehabilitation motion and external force trajectories.

  10. Towards structure-based protein drug design.

    PubMed

    Zhang, Changsheng; Lai, Luhua

    2011-10-01

    Structure-based drug design for chemical molecules has been widely used in drug discovery in the last 30 years. Many successful applications have been reported, especially in the field of virtual screening based on molecular docking. Recently, there has been much progress in fragment-based as well as de novo drug discovery. As many protein-protein interactions can be used as key targets for drug design, one of the solutions is to design protein drugs based directly on the protein complexes or the target structure. Compared with protein-ligand interactions, protein-protein interactions are more complicated and present more challenges for design. Over the last decade, both sampling efficiency and scoring accuracy of protein-protein docking have increased significantly. We have developed several strategies for structure-based protein drug design. A grafting strategy for key interaction residues has been developed and successfully applied in designing erythropoietin receptor-binding proteins. Similarly to small-molecule design, we also tested de novo protein-binder design and a virtual screen of protein binders using protein-protein docking calculations. In comparison with the development of structure-based small-molecule drug design, we believe that structure-based protein drug design has come of age.

  11. 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.

  12. 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.

  13. 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

  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.

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

    PubMed

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

    2017-06-01

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

  16. 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.

  17. Computer Aided Design Of Electrical Machines For Variable Speed Applications.

    NASA Astrophysics Data System (ADS)

    Krishnan, R.; Aravind, S.; Materu, P.

    1987-10-01

    In recent years, the product life cycle has decreased and demands for new products have emerged due to competition, modern industrial needs and rapidly changing technology. This has necessitated changes in design, development and manufacturing processes so as to improve quality and efficiency as well as reducing costs. Computer Aided Design (CAD) helps to meet this challenge in the design evaluation and final product design stages. This paper presents the development of an interactive software for the optimal design of a motor intended for variable speed applications. The use of finite element analysis methods is proposed as an indispensable part of the CAD system for electrical machine design. An illustration of the method is given for the design of a switched reluctance motor.

  18. Navigation and Alignment Aids Concept of Operations and Supplemental Design Information. Revision A

    NASA Technical Reports Server (NTRS)

    Kelly, Sean M.; Cryan, Scott P.

    2016-01-01

    The IDSS Navigation and Alignment Aids Concept of Operations and Supplemental Design Information document provides supplemental information to the IDSS IDD. The guide provides insight into the navigation and alignment aids design, and how those aids can be utilized by incoming vehicles for proximity operations and docking. The navigation aids are paramount to successful docking.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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…

  4. RAMCAD (Reliability, Availability and Maintainability in Computer-Aided Design)

    DTIC Science & Technology

    1992-11-01

    documents the Reliability, Availability, and Maintainability in Computer-Aided Design (RAMCAD) Software Development Program which was started in July 1986 ...by General Dynamics Convair Division under a Program Research and Development Announcement (PRDA 86-16-PMRS). This PRDA was issued on May 15, 1986 ...PRDA 86-16-PMRS) was issued on May 15, 1986 , by the Air Force Human Resources ..aboratory (AFHRL, changed to Armstrong Laboratory, Human Resources

  5. Computer-Aided Final Design Cost Estimating System Overview.

    DTIC Science & Technology

    1977-05-01

    laboratory _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ /1— COMPUTER-AIDED FINAL DESIGN • COST ESTIMATING SYSTEM OVERVIEW © by...PROJECT . TASKAAEA~~ WORK UNIT NUMBERSCONSTRUCTION ENGINEERING RESEARCH LABORATORY ~~~~~~~~~ .• . — P.O. Box 4005 ~~ 4A7627~ %T4fldt11 Champa ign , IL 61820...Construction Division (FA), U.S. Army Construction Engineering Re- search Laboratory (CERL), Champaign , IL. The Principal Investigator was Mr. Michael

  6. From laptop to benchtop to bedside: structure-based drug design on protein targets.

    PubMed

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

    2012-01-01

    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 proteinligand 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.

  7. 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

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. Perceived AIDS risk among adult arrestee injection drug users in Los Angeles county.

    PubMed

    Henson, K D; Longshore, D; Kowalewski, M R; Anglin, M D; Annon, K

    1998-10-01

    In this paper we examine the determinants of perceived risk for getting HIV and AIDS among adult Los Angeles arrestees reporting any lifetime injection drug use (N = 958). Our sample, drawn from the Drug Use Forecasting program, is 60% male and 40% female. Higher rates of reported risky drug and sexual behaviors than in the general population make this a particularly relevant sample within which to explore correlates of perceived risk for getting HIV and AIDS. We used multiple logistic regression to assess the relationship between perceived risk and a variety of demographic, behavioral, and psychosocial variables. Arrestees reporting celibacy in the past year, having an injection-drug-using sexual partner, having more than 20 sexual partners, engaging in sex while high, knowing someone with AIDS, and having been tested for HIV antibodies were more likely to perceive themselves at greater risk of getting HIV and AIDS. African American arrestees and arrestees reporting having attempted to reduce their sexual risks were less likely to perceive themselves at greater risk for getting AIDS. Implications for AIDS education and prevention are discussed.

  13. 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.

  14. Designer drugs: a medicinal chemistry perspective.

    PubMed

    Carroll, F Ivy; Lewin, Anita H; Mascarella, S Wayne; Seltzman, Herbert H; Reddy, P Anantha

    2012-02-01

    There are numerous medicinal chemistry reports in the literature describing the pharmacological properties of thousands of narcotics, stimulants, hallucinogens, sedative-hypnotic drugs, cannabinoids, and other psychoactive substances as well as synthetic methods for their preparations. This information, while essential for the advancement of science, has been used by clandestine chemists to manufacture and market an endless variety of analogs of so-called designer drugs. In this review, we describe how clandestine chemists used the principles of medicinal chemistry to design molecules, referred to as designer drugs, that elicit the effects of opioids, amphetamine and analogs, cannabinoids, and phencyclidine analogs while circumventing the law.

  15. AIDS

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000594.htm HIV/AIDS To use the sharing features on this page, ... immunodeficiency virus (HIV) is the virus that causes AIDS. When a person becomes infected with HIV, the ...

  16. 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.

  17. 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.

  18. 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.

  19. 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 Marijuana Marijuana as Medicine MDMA (Ecstasy/Molly) ...

  20. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Timing of requests for orphan-drug designation; designation of already approved drugs. 316.23 Section 316.23 Food and Drugs FOOD AND DRUG...

  1. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Timing of requests for orphan-drug designation; designation of already approved drugs. 316.23 Section 316.23 Food and Drugs FOOD AND DRUG...

  2. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) A sponsor may request orphan-drug designation at any time in its drug development process prior to... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Timing of requests for orphan-drug designation; designation of already approved drugs. 316.23 Section 316.23 Food and Drugs FOOD AND DRUG...

  3. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Timing of requests for orphan-drug designation; designation of already approved drugs. 316.23 Section 316.23 Food and Drugs FOOD AND DRUG...

  4. 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

    ...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Timing of requests for orphan-drug designation; designation of already approved drugs. 316.23 Section 316.23 Food and Drugs FOOD AND DRUG...

  5. 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.…

  6. 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.

  7. 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.

  8. 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.

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

    PubMed

    Kang, Sang-Hoon; Kim, Moon-Key; Lee, Ji-Yeon

    2016-04-01

    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.

  10. 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)…

  11. Retrofitting a crown to a sleep apnea device by using computer-aided design and computer-aided milling technology.

    PubMed

    Biethman, Rick; Land, Martin F; Hruskocy, Heather; Colgin, Bruce

    2014-07-01

    Retrofitting a new crown to an existing dental device is challenging. The continued evolution of computer-aided design and computer-aided manufacturing (CAD/CAM) significantly simplifies the process. This article demonstrates retrofitting a gold crown to an existing sleep apnea device.

  12. 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

  13. 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.

  14. Psychological assessment and AIDS research with intravenous drug users: challenges in measurement.

    PubMed

    Huang, K H; Watters, J K; Case, P

    1988-01-01

    The instruments used for psychological assessment have been under close scrutiny for many years. In particular, ethnic and racial minorities have pointed out that misapplication of instruments standardized to White middle-class norms can result in incorrect assessments. An analogous situation exists with IVDUs. In the work of the present authors with IVDUs, they were found to be a very diverse group. Contrary to common wisdom, they differ by race, ethnicity, age, and drug use profiles. However, their economic circumstances and social stigma make them a special case in terms of psychological assessment. Given the unique characteristics of IVDUs, it behooves researchers to carefully examine the standardized instruments that are available for psychological evaluation. Too often, measures standardized on White middle-class samples lack the value neutrality that makes them applicable across disparate groups. In addition, many such measures are designed with certain presumptions that do not necessarily hold true with this population (e.g., willingness and/or ability to communicate intimate information about one's feelings and psychological states). This article briefly describes some of the challenges encountered in examining standardized instruments for use in the study of IVDUs, their health psychology and AIDS-related behavior. Concerns with self-report biases, literacy, attentional focus, measurement constructs, and drug states confounding psychological states all pose challenges to psychological research with this heterogeneous population. While the need for direct intervention on the sexual and needle-sharing behaviors of IVDUs remains paramount in the combat against the spread of AIDS, researchers must also continue with the further development of basic measurement tools.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Analyzing HIV/AIDS and Alcohol and Other Drug Use as a Social Problem

    PubMed Central

    PATTERSON, DAVID A.; Wolf (Adelv unegv Waya), Silver

    2012-01-01

    Most prevention and intervention activities directed toward HIV/AIDS and alcohol and other drug use separately as well as the combining of the two (e.g., those who are both HIV/AIDS and using alcohol and other drugs) comes in the form of specific, individualized therapies without consideration of social influences that may have a greater impact on this population. Approaching this social problem from the narrowed view of individualized, mi-cro solutions disregards the larger social conditions that affect or perhaps even are at the root of the problem. This paper analyzes the social problem of HIV/AIDS and alcohol and other drug abuse using three sociological perspectives—social construction theory, ethnomethodology, and conflict theory—informing the reader of the broader influences accompanying this problem. PMID:23264724

  16. Substance Abuse Treatment, HIV/AIDS, and the Continuum of Response for People Who Inject Drugs

    PubMed Central

    Kresina, Thomas F.; Lubran, Robert; Clark, H. Westley; Cheever, Laura W.

    2012-01-01

    The continuum of response (CoR) to HIV/AIDS is a framework for implementation of HIV prevention, care, and treatment programs based on a national strategic plan for HIV/AIDS services. The CoR for people who inject drugs (PWID) is an important extension of the developed CoR to HIV/AIDS. The CoR-PWID employs stakeholders who together plan, develop, pilot, and provide a full range of services that address the various prevention, care/support, and treatment needs of people, families, and communities infected or affected by HIV/AIDS and injection drug use. The CoR-PWID comprises a broad range of services that include but are not limited to the World Health Organization priority interventions for HIV/AIDS prevention, treatment, and care in the health sector and the package of essential interventions for the prevention, treatment, and care of HIV for people who inject drugs. Implementation of these well-defined, essential prevention, care/support, and treatment services, in addition to locally defined needed services, in a coordinated fashion is important to clients, their families, and communities. The CoR-PWID is, therefore, a necessary framework essential for service development for countries that address HIV/AIDS in populations of PWID. PMID:23243517

  17. 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.

  18. 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.

  19. Designing hydrogels for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Li, Jianyu; Mooney, David J.

    2016-12-01

    Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform on which various physiochemical interactions with the encapsulated drugs occur to control drug release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.

  20. Biologically inspired binaural hearing aid algorithms: Design principles and effectiveness

    NASA Astrophysics Data System (ADS)

    Feng, Albert

    2002-05-01

    Despite rapid advances in the sophistication of hearing aid technology and microelectronics, listening in noise remains problematic for people with hearing impairment. To solve this problem two algorithms were designed for use in binaural hearing aid systems. The signal processing strategies are based on principles in auditory physiology and psychophysics: (a) the location/extraction (L/E) binaural computational scheme determines the directions of source locations and cancels noise by applying a simple subtraction method over every frequency band; and (b) the frequency-domain minimum-variance (FMV) scheme extracts a target sound from a known direction amidst multiple interfering sound sources. Both algorithms were evaluated using standard metrics such as signal-to-noise-ratio gain and articulation index. Results were compared with those from conventional adaptive beam-forming algorithms. In free-field tests with multiple interfering sound sources our algorithms performed better than conventional algorithms. Preliminary intelligibility and speech reception results in multitalker environments showed gains for every listener with normal or impaired hearing when the signals were processed in real time with the FMV binaural hearing aid algorithm. [Work supported by NIH-NIDCD Grant No. R21DC04840 and the Beckman Institute.

  1. 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.

  2. 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.

  3. 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

  4. Designer Drugs: A Synthetic Catastrophe.

    PubMed

    Fratantonio, James; Andrade, Lawrence; Febo, Marcelo

    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.

  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. Computer Aided Antenna Design and Frequency Selection for HF Communications.

    DTIC Science & Technology

    1984-06-01

    EESIGN ON THE ADPE-.- NIF (GREEN MACHINE) ... .... . . . . . . . 57 E. COMPUTER AIDED DESIGN USING ECAC1S ACCESSIBIE ANTENNA PACKAGE . . . . . . .. 57 F...8217 C8 L4 E-4 W 3a ’H 1 H -g I) - 4 ’ 0-4 =2 E-4 V. E-4 b. m 0 m 4 =- v- -4 3 4 E’- 4 = P4 H - ofC. I- 1 4 = W P4 w 4 I = N = V rq I 0-4 ~ to H W4

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    PubMed

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

    2016-05-23

    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.

  12. Medication assisted treatment in the treatment of drug abuse and dependence in HIV/AIDS infected drug users.

    PubMed

    Kresina, Thomas F; Bruce, R Douglas; McCance-Katz, Elinore F

    2009-07-01

    Drug use and HIV/AIDS are global public health issues. The World Health Organization (WHO) estimates that up to 30% of HIV infections are related to drug use and associated behaviors. The intersection, of the twin epidemics of HIV and drug/alcohol use, results in difficult medical management issues for the health care providers and researchers who work in the expanding global HIV prevention and treatment fields. Access to care and treatment, medication adherence to multiple therapeutic regimens, and concomitant drug -drug interactions of prescribed treatments are difficult barriers for drug users to overcome without directed interventions. Injection drug users are frequently disenfranchised from medical care and suffer sigma and discrimination creating additional barriers to care and treatment for their drug abuse and dependence as well as HIV infection. In an increasing number of studies, medication assisted treatment of drug abuse and dependence has been shown to be an important HIV prevention intervention. Controlling the global transmission of HIV will require further investment in evidence-based interventions and programs to enhance access to care and treatment of individuals who abuse illicit drugs and alcohol. In this review, we present the cumulative evidence of the importance of medication assisted treatment in the prevention, care, and treatment of HIV infected individuals who also abuse drugs and alcohol.

  13. 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.

  14. Computational Methods Applied to Rational Drug Design.

    PubMed

    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.

  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. 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.

  17. 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

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

    PubMed

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

    2011-03-14

    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.

  19. 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

  20. 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.

  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. 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

  3. 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.

  4. Design of Adverse Drug Events-Scorecards.

    PubMed

    Marcilly, Romaric; Chazard, Emmanuel; Beuscart-Zéphir, Marie-Catherine; Hackl, Werner; Băceanu, Adrian; Kushniruk, Andre; Borycki, Elizabeth M

    2011-01-01

    This paper presents the design of Adverse Drug Event-Scorecards. The scorecards described are innovative and novel, not having previously been reported in the literature. The Scorecards provide organizations (e.g. hospitals) with summary information about Adverse Drug Events (ADEs) using a Web-based platform. The data used in the Scorecards are routinely updated and report on ADEs detected through data mining processes. The development of the ADE Scorecards is ongoing and they are currently undergoing clinical testing.

  5. HIV / AIDS in China: migrant population, drug injection responsible for increased transmission.

    PubMed

    Thomas, J

    1998-01-01

    By 2000, China will have 1.2 million people infected with HIV and 33,000 people with AIDS. While HIV infection has been reported from almost all provinces and occupational groups in the country, HIV prevalence is highest among IV drug users in Yunnan province. The major source of infection elsewhere in China is through the receipt of tainted blood products and heterosexual intercourse. A National AIDS Committee was formed in October 1986 to advise the government on AIDS policy, and since 1990 to coordinate all AIDS prevention activities. The National Strategies Plan for AIDS/STD Prevention in China during 1996-2000 was prepared in 1995. China's in-country migrant labor population may become the most vulnerable to HIV infection. There are currently about 120 million migrant workers in China, of whom about half are registered, nonpermanent residents working in the fastest developing regions. The open nature of China's economy relative to recent past decades has made it difficult to monitor and control internal migration. Floating populations are the most difficult to reach with preventive health education and they tend to be deprived of access of health care. 61.4% of the migrant population is male and 40% are aged 20-24 years. China's traditional trade routes may be a factor in HIV infection. HIV/AIDS epidemiology, the synergy of STDs and AIDS in China, the international partnership in HIV/AIDS prevention in China, the role of international nongovernmental organizations in China, Hong Kong's contribution to AIDS prevention in China, awareness of the problems associated with HIV infection in China, and the challenges for AIDS-related work in China are discussed.

  6. AIDS knowledge and attitudes among injection drug users: the issue of reliability.

    PubMed

    Longshore, D; Hsieh, S C; Anglin, M D

    1992-01-01

    Among injection drug users (IDUs), AIDS-related knowledge and attitudes have not consistently predicted AIDS risk behavior. This may be due in part to the limited reliability of indexes used to measure drug users' AIDS knowledge and attitudes. In addition, the substantive interpretation of findings is confounded if index reliability is lower for particular demographic groups (e.g., ethnic populations and women). This report is based on 8 measures of AIDS-related knowledge and attitudes in a sample of 332 injection drug users in Los Angeles. The reliability of knowledge and attitude indexes for the overall sample is generally acceptable for the purpose of group comparison (average alpha = .60). But reliability is consistently lower for respondents who are Hispanic (average alpha = .49) and respondents with less formal education (alpha = .56). The reliability of 2 measures of sex-related attitudes is lower for female respondents. It is therefore important that the reliability of knowledge and attitude indexes be assessed not just for drug-user samples as a whole, but also within demographic groups of substantive interest.

  7. 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.

  8. 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...

  9. 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...

  10. 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...

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Sustained AIDS education campaigns and behavioural changes in Italian drug abusers.

    PubMed

    Bortolotti, F; Stivanello, A; Noventa, F; Forza, G; Pavanello, N; Bertolini, A

    1992-03-01

    In the area of Padua, northern Italy, fear of AIDS along with AIDS educational campaigns had reduced risk behaviours for HIV among intravenous drug abusers (IVDA) as early as 1987, although at that time 38% of seropositive cases still shared needles and only 22% of subjects used condoms. The present study has been conducted in the same area and with similar criteria to evaluate the effectiveness and limits of a sustained education campaign. Drug related and sexual risk behaviours and motivations preventing behavioural changes were investigated by direct interview in 190 IVDA. Fourteen percent of the participants, including 16% of the seropositive, were still sharing needles, mainly because they did not have works available at the time they were needed. Demographic features, drug-related characteristics and anti-HIV seroprevalence did not differ significantly between needlesharers and other drug abusers. Condom use was reported by 46% of subjects, but encouragingly enough this figure included 80% of the seropositives. While knowledge of seropositivity seemed to encourage condom use, a higher selectivity about partners and a negative attitude towards condoms were the most frequent motivations preventing safer sex. These results suggest that sustained AIDS education campaigns are being successful in maintaining and reinforcing the trend to risk reduction previously observed among drug abusers in this area. Nevertheless the persistence of risk behaviours in a consistent proportion of participants emphasizes the urgency of additional prevention strategies, such as syringe exchange or supply to the limited number of sharers and counselling to encourage safer sex.

  16. 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

  17. Taking a break from chemotherapy to fight drug-resistance: The cases of cancer and HIV/AIDS.

    PubMed

    Hadjiandreou, Marios M; Mitsis, Georgios D

    2013-01-01

    In this work, we present how optimized treatment interruptions during chemotherapy may be used to control drug-resistance, a major challenge for clinicians worldwide. Specifically, we examine resistance in cancer and HIV/AIDS. For each disease, we use mathematical models alongside real data to represent the respective complex biological phenomena and optimal control algorithms to design optimized treatment schedules aiming at controlling disease progression and patient death. In both diseases, it is shown that the key to controlling resistance is the optimal management of the frequency and magnitude of treatment interruptions as a way to facilitate the interplay between the competitive resistant/sensitive strains.

  18. 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

  19. 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.

  20. FAPA mass spectrometry of designer drugs.

    PubMed

    Smoluch, Marek; Gierczyk, Blazej; Reszke, Edward; Babij, Michal; Gotszalk, Teodor; Schroeder, Grzegorz; Silberring, Jerzy

    2016-01-01

    Application of a flowing atmospheric-pressure afterglow ion source for mass spectrometry (FAPA-MS) for the analysis of designer drugs is described. In this paper, we present application of FAPA MS for identification of exemplary psychotropic drugs: JWH-122, 4BMC, Pentedrone, 3,4-DNNC and ETH-CAT. We have utilized two approaches for introducing samples into the plasma stream; first in the form of a methanolic aerosol from the nebulizer, and the second based on a release of vapors from the electrically heated crucible by thermal desorption. The analytes were ionized by FAPA and identified in the mass analyzer. The order of release of the compounds depends on their volatility. These methods offer fast and reliable structural information, without pre-separation, and can be an alternative to the Electron Impact, GC/MS, and ESI for fast analysis of designer-, and other psychoactive drugs.

  1. 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.

  2. Machine learning techniques and drug design.

    PubMed

    Gertrudes, J C; Maltarollo, V G; Silva, R A; Oliveira, P R; Honório, K M; da Silva, A B F

    2012-01-01

    The interest in the application of machine learning techniques (MLT) as drug design tools is growing in the last decades. The reason for this is related to the fact that the drug design is very complex and requires the use of hybrid techniques. A brief review of some MLT such as self-organizing maps, multilayer perceptron, bayesian neural networks, counter-propagation neural network and support vector machines is described in this paper. A comparison between the performance of the described methods and some classical statistical methods (such as partial least squares and multiple linear regression) shows that MLT have significant advantages. Nowadays, the number of studies in medicinal chemistry that employ these techniques has considerably increased, in particular the use of support vector machines. The state of the art and the future trends of MLT applications encompass the use of these techniques to construct more reliable QSAR models. The models obtained from MLT can be used in virtual screening studies as well as filters to develop/discovery new chemicals. An important challenge in the drug design field is the prediction of pharmacokinetic and toxicity properties, which can avoid failures in the clinical phases. Therefore, this review provides a critical point of view on the main MLT and shows their potential ability as a valuable tool in drug design.

  3. 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.

  4. Converting Between PLY and Ballistic Research Laboratory-Computer-Aided Design (BRL-CAD) File Formats

    DTIC Science & Technology

    2015-02-01

    Converting Between PLY and Ballistic Research Laboratory–Computer-Aided Design (BRL-CAD) File Formats by Rishub Jain ARL-CR-0760...0760 February 2015 Converting Between PLY and Ballistic Research Laboratory–Computer-Aided Design (BRL-CAD) File Formats Rishub Jain US...and Ballistic Research Laboratory–Computer-Aided Design (BRL-CAD) File Formats 5a. CONTRACT NUMBER W911NF-10-2-0076 5b. GRANT NUMBER 5c. PROGRAM

  5. Target Impact Detection Algorithm Using Computer-aided Design (CAD) Model Geometry

    DTIC Science & Technology

    2014-09-01

    UNCLASSIFIED AD-E403 558 Technical Report ARMET-TR-13024 TARGET IMPACT DETECTION ALGORITHM USING COMPUTER-AIDED DESIGN ( CAD ...DETECTION ALGORITHM USING COMPUTER-AIDED DESIGN ( CAD ) MODEL GEOMETRY 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...This report documents a method and algorithm to export geometry from a three-dimensional, computer-aided design ( CAD ) model in a format that can be

  6. 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

  7. Rational drug design applied to myeloperoxidase inhibition.

    PubMed

    Van Antwerpen, P; Zouaoui Boudjeltia, K

    2015-06-01

    Rational drug design is a general approach using protein-structure technique in which the discovery of a ligand can be driven either by chance, screening, or rational theory. Myeloperoxidase (MPO) was rapidly identified as a therapeutical target because of its involvement in chronic inflammatory syndromes. In this context, the research of MPO inhibitors was intensified and development of new chemical entities was rationally driven by the research of ligands that enter into the MPO catalytic pocket. Actually, as soon as crystallography data of MPO have become available and its structure was virtually designed, the rational drug design has been applied to this peroxidase. Pharmaceutical industries and academic laboratories apply rational drug design on MPO by either optimizing known inhibitors or searching new molecules by high-throughput virtual screening. By these ways, they were able to find efficient MPO inhibitors and understand their interactions with the enzyme. During this quest of MPO inhibition, it appears that Glu268 is a crucial residue in order to optimize ligand-target interaction. This amino acid should be carefully considered by medicinal chemist when they design inhibitors interfering with MPO activity.

  8. An analysis of drug resistance among people living with HIV/AIDS in Shanghai, China

    PubMed Central

    Sun, Meiyan; Sun, Jianjun; Lu, Hongzhou

    2017-01-01

    Background Understanding the mechanisms of drug resistance can facilitate better management of antiretroviral therapy, helping to prevent transmission and decrease the morbidity and mortality of people living with HIV/AIDS. However, there is little data about transmitted drug resistance and acquired drug resistance for HIV/AIDS patients in Shanghai. Methods A retrospective cohort study of HIV-infected patients who visited the Department of Infectious Disease from June 2008 to June 2015 was conducted in Shanghai, China. Logistic regression analysis was performed to analyze risk factors for drug resistance among HIV-infected people with virological failure. The related collected factors included patient age, gender, marital status, infection route, baseline CD4 count, antiretroviral therapy regimens, time between HIV diagnosis and initiating antiretroviral therapy. Factors with p<0.1 in the univariate logistic regression test were analyzed by multivariate logistic regression test. Results There were 575 subjects selected for this study and 369 participated in this research. For the antiretroviral therapy drugs, the rates of transmitted drug resistance and acquired drug resistance were significantly different. The non-nucleoside reverse transcriptase inhibitor (NNRTI) had the highest drug resistance rate (transmitted drug resistance, 10.9%; acquired drug resistance, 53.3%) and protease inhibitors (PIs) had the lowest drug resistance rate (transmitted drug resistance, 1.7%; acquired drug resistance, 2.7%). Logistic regression analysis found no factors that were related to drug resistance except marital status (married status for tenofovir: odds ratio = 6.345, 95% confidence interval = 1.553–25.921, P = 0.010) and the time span between HIV diagnosis and initiating antiretroviral therapy (≤6M for stavudine: odds ratio = 0.271, 95% confidence interval = 0.086–0.850, P = 0.025; ≤6M for didanosine: odds ratio = 0.284, 95% confidence interval = 0.096–0.842, P = 0

  9. 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.

  10. 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

  11. 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.

  12. Advertising for AIDS drugs: it's everywhere lately, but is it helpful?

    PubMed

    Mirken, B

    1998-07-01

    The recent proliferation of direct to consumer (DTC) advertisements for prescription drugs, including HIV/AIDS drugs, can present a confusing and unrealistic picture of treatment options and outcomes; however, supporters claim that it stimulates awareness of treatment options and encourages dialogue between doctors and patients. The Food and Drug Administration (FDA), which regulates DTC advertising, requires that manufacturers disclose a complete description of benefits and adverse effects, similar to the information on the product's label. This balance of information applies to the written portion of the ad, but not to the visual message, which is arguably the most powerful part of the advertisement. Many of the visuals in the AIDS drugs advertisements misconstrue the effect of the virus on the patients. However, the FDA has not yet developed restrictions to more accurately control the visual component of advertisements, in order to depict the downside of disease. Additionally, manufacturers whose advertisements match the wording on their labels have an easier time getting acceptance from the FDA, but use more technical language than the typical lay person can understand. Reliance on the FDA- approved label description, restricts the drug companies from promoting off-label uses of their products, and also does not allow for the constantly changing information of a drug's effectiveness.

  13. Chemogenomic approaches to rational drug design

    PubMed Central

    Rognan, D

    2007-01-01

    Paradigms in drug design and discovery are changing at a significant pace. Concomitant to the sequencing of over 180 several genomes, the high-throughput miniaturization of chemical synthesis and biological evaluation of a multiple compounds on gene/protein expression and function opens the way to global drug-discovery approaches, no more focused on a single target but on an entire family of related proteins or on a full metabolic pathway. Chemogenomics is this emerging research field aimed at systematically studying the biological effect of a wide array of small molecular-weight ligands on a wide array of macromolecular targets. Since the quantity of existing data (compounds, targets and assays) and of produced information (gene/protein expression levels and binding constants) are too large for manual manipulation, information technologies play a crucial role in planning, analysing and predicting chemogenomic data. The present review will focus on predictive in silico chemogenomic approaches to foster rational drug design and derive information from the simultaneous biological evaluation of multiple compounds on multiple targets. State-of-the-art methods for navigating in either ligand or target space will be presented and concrete drug design applications will be mentioned. PMID:17533416

  14. 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.

  15. The fourth Okey memorial lecture. AIDS and HIV: the challenge for British drug services.

    PubMed

    Stimson, G V

    1990-03-01

    British drug policies are undergoing a major reassessment and reformulation in response to problems raised by HIV disease and AIDS. The years from 1986 to 1989 are one of the key periods of crisis and transformation in the history of the British response to drug problems, with the emergence in current debate of a new public health paradigm of drug use. Drug policies can be analysed by examining their assumptions about the nature of (a) the problem (b) the drug user and (c) the task facing policy makers and practitioners; and their assumption about (d) the appropriate people to deal with the problem and (e) their relationships with clients. The emergent public health paradigm assumes that (a) the main problem with drug use is the injection of drugs (b) drug injectors are concerned about their health (c) the task is to promote change in health and risk behaviours (d) people dealing with the problem must be broadly skilled 'poly-drug workers' and (e) relationships with clients must be non-judgmental and 'user-friendly'.

  16. 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.

  17. Determination of designer drug cross-reactivity on five commercial immunoassay screening kits.

    PubMed

    Regester, Laura E; Chmiel, Jeffrey D; Holler, Justin M; Vorce, Shawn P; Levine, Barry; Bosy, Thomas Z

    2015-03-01

    The detection of new designer drugs is often a difficult issue in forensic urine drug testing as immunoassays are the primary screening methodology for drugs of abuse in many of these laboratories. Cross-reactivity of compounds with immunoassay kits can either aid or complicate the detection of a variety of drug and drug metabolites. For instance, emerging designer drugs that share structural similarities to amphetamines and phencyclidine (PCP) have the potential to cross-react with assays designed to detect these compounds. This study evaluates the cross-reactivity of five commercially available immunoassay reagent kits for 94 designer drugs on a Roche/Hitachi Modular P automated screening instrument. The compounds used in this study are grouped by structural class as follows: 2,5-dimethoxyamphetamines, 2C (2,5-dimethoxyphenethylamines), β-keto amphetamines, substituted amphetamines, piperazines, α-pyrrolidinopropiophenones, tryptamines and PCP analogs. A drug concentration of 100 µg/mL was used to determine cross-reactivity for each assay and resulted in the following positive rates: Microgenics DRI(®) Ecstasy enzyme assay (19%), Microgenics DRI(®) Phencyclidine enzyme assay (20%), Lin-Zhi Methamphetamine enzyme immunoassay (39%), Siemens/Syva(®) EMIT(®)II Plus Amphetamines assay (43%) and CEDIA(®) DAU Amphetamine/Ecstasy assay (57%). Of the 94 designer drugs tested, 14% produced a negative response for all five kits. No designer drug used in this study generated a positive result for all five immunoassay kits.

  18. Selection and Characterization of Drug-Resistant Variants of Human Immunodeficiency Virus (AIDS).

    DTIC Science & Technology

    1995-10-01

    resis- nitis in patients with AIDS. It is also the current drug of choice tance to all other selective reverse transcriptase (RT) inhibi- for acyclovir ...used to-treat acyclovir -resistant herpes simplex 8,18) (Erlich et al., 1989; Birch et at, 11990; Safrin et a!, 1991ib) Beas ccrnthsnieroraatviyndi and...immuriodeficiericy virus: Inhibition by cournermycin Al. Ant ,vral comparing fimcarnel with vidarabine for acyclovir -fesislant mucocu- Chein. Chemather. 1

  19. Drug design from the cryptic inhibitor envelope.

    PubMed

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

    2016-02-25

    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.

  20. 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

  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. Exploiting protein intrinsic flexibility in drug design.

    PubMed

    Lukman, Suryani; Verma, Chandra S; Fuentes, Gloria

    2014-01-01

    Molecular recognition in biological systems relies on the existence of specific attractive interactions between two partner molecules. Structure-based drug design seeks to identify and optimize such interactions between ligands and their protein targets. The approach followed in medicinal chemistry follows a combination of careful analysis of structural data together with experimental and/or theoretical studies on the system. This chapter focuses on the fact that a protein is not fully characterized by a single structure, but by an ensemble of states, some of them represent "hidden conformations" with cryptic binding sites. We highlight case studies where both experimental and computational methods have been used to mutually drive each other in an attempt to improve the success of the drug design approaches.Advances in both experimental techniques and computational methods have greatly improved our physico-chemical understanding of the functional mechanisms in biomolecules and opened a debate about the interplay between molecular structure and biomolecular function. The beautiful static pictures of protein structures may have led to neglecting the intrinsic protein flexibility, however we are entering a new era where more sophisticated methods are used to exploit this ability of macromolecules, and this will definitely lead to the inclusion of the notion in the pharmaceutical field of drug design.

  5. 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…

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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,...

  15. 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,...

  16. 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,...

  17. 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,...

  18. 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,...

  19. 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...

  20. Computational thermodynamics aided design of novel ferritic alloys

    SciTech Connect

    Yang, Ying; Chen, Tianyi; Tan, Lizhen

    2016-06-30

    With the aid of computational thermodynamics, Ni was identified to suppress the liquidus temperature of Fe2Zr and four Fe-Cr-Ni-Zr alloys were designed to study the Ni effect on the phase stability of Fe2Zr laves_phase. These alloys were fabricated through traditional arc-metling, followed by annealing at 1000 C for 336 hours and 700 C for 1275 hours. The microstructure were examined and characterized by SEM BSE image, EDS compositional mapping and point scan, XRD and TEM analysis. The major results were summarized below: 1)For investigated alloys with 12wt% Cr, 3~6wt% Zr and 3~9 wt%Ni, the phases in equilibrium with the BCC phase are C15_Laves phase, Fe23Zr6 phase. The volume fraction of intermetallic phases increases with Ni and Zr contents. 2)Instead of (Fe,Cr)2Zr C14_Laves phase, Ni stabilizes the C15_Laves structure in Fe-Cr-Ni-Zr alloys by substituting Fe and Cr atoms with Ni atoms in the first sublattice. 3)Fe23Zr6, that is metastable in the Fe-Cr-Zr ternary, is also stabilized by Ni addition. 4)Ni7Zr2 phase was observed in samples with high Ni/Zr ratio. Extensive solubility of Fe was identified in the phase. The microstructural and composition results obtained from this study will be incorportated into the the Fe-Cr-Ni-Zr database. The current samples will be subjected to ion irradiaition to be compared with those results for Fe-Cr-Zr alloys. Additional alloys will be designed to form (Fe,Cr,Ni)2Zr nanoprecipitates for further studies.

  1. 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

  2. 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…

  3. Multilevel Predictors of Concurrent Opioid Use during Methadone Maintenance Treatment among Drug Users with HIV/AIDS

    PubMed Central

    Tran, Bach Xuan; Ohinmaa, Arto; Mills, Steve; Duong, Anh Thuy; Nguyen, Long Thanh; Jacobs, Philip; Houston, Stan

    2012-01-01

    Background Ongoing drug use during methadone maintenance treatment (MMT) negatively affects outcomes of HIV/AIDS care and treatment for drug users. This study assessed changes in opioid use, and longitudinal predictors of continued opioid use during MMT among HIV-positive drug users in Vietnam, with the aim of identifying changes that might enhance program efficacy. Methods We analyze data of 370 HIV-positive drug users (mean age 29.5; 95.7% male) taking MMT at multi-sites. Opioid use was assessed at baseline, 3, 6, and 9 months using interviews and heroin confirmatory urine tests. A social ecological model was applied to explore multilevel predictors of continued opioid use, including individual, interpersonal, community and service influences. Generalized estimating equations (GEE) statistical models were constructed to adjust for intra-individual correlations. Results Over 9 month follow-up, self-reported opioid use and positive heroin urine test substantially decreased to 14.6% and 14.4%. MMT helped improve referrals and access to health care and social services. However, utilization of social integration services was small. GEE models determined that participants who were older (Adjusted Odd Ratio - AOR = 0.97 for 1 year increase), had economic dependents (AOR = 0.33), or were referred to TB treatment (AOR = 0.53) were less likely to continue opioid use. Significant positive predictors of ongoing opioid use included frequency of opioid use prior to MMT, peer pressure, living with sexual partners, taking antiretroviral treatment, other health concerns and TB treatment. Conclusion These findings show that MMT in the Vietnamese context can dramatically reduce opioid use, which is known to be associated with reduced antiretroviral (ART) adherence. Disease stage and drug interactions between antiretrovirals or TB drugs and MMT could explain some of the observed predictors of ongoing drug use; these findings could inform changes in MMT program design and

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. An AIDS model with distributed incubation and variable infectiousness: applications to i.v. drug users in Latium, Italy.

    PubMed

    Iannelli, M; Loro, R; Milner, F; Pugliese, A; Rabbiolo, G

    1992-07-01

    An AIDS model with distributed incubation and variable infectiousness is considered and simulated via a second-order numerical method. The method is applied to the HIV epidemic among IV drug users in the Latium region of Italy, using available data on the length of the incubation period before the onset of AIDS, on the infectivity of infected individuals during that period, and on the demography of drug users. The contact rate is adjusted to match the actual number of AIDS cases. The sensitivity of the model to uncertainties in the parameters is finally investigated, by performing several simulations.

  10. Out-of-pocket costs of AIDS care in China: are free antiretroviral drugs enough?

    PubMed

    Moon, S; Van Leemput, L; Durier, N; Jambert, E; Dahmane, A; Jie, Y; Wu, G; Philips, M; Hu, Y; Saranchuk, P

    2008-09-01

    Financial access to HIV care and treatment can be difficult for many people in China, where the government provides free antiretroviral drugs but does not cover the cost of other medically necessary components, such as lab tests and drugs for opportunistic infections. This article estimates out-of-pocket costs for treatment and care that a person living with HIV/AIDS in China might face over the course of one year. Data comes from two treatment projects run by Médecins Sans Frontières in Nanning, Guangxi Province and Xiangfan, Hubei Province. Based on the national treatment guidelines, we estimated costs for seven different patient profiles ranging from WHO Clinical Stages I through IV. We found that patients face significant financial barriers to even qualify for the free ARV program. For those who do, HIV care and treatment can be a catastrophic health expenditure, with cumulative patient contributions ranging from approximately US$200-3939/year in Nanning and US$13-1179/year in Xiangfan, depending on the patient's clinical stage of HIV infection. In Nanning, these expenses translate as up to 340% of an urban resident's annual income or 1200% for rural residents; in Xiangfan, expenses rise to 116% of annual income for city dwellers and 295% in rural areas. While providing ARV drugs free of charge is an important step, the costs of other components of care constitute important financial barriers that may exclude patients from accessing appropriate care. Such barriers can also lead to undesirable outcomes in the future, such as impoverishment of AIDS-affected households, higher ARV drug-resistance rates and greater need for complex, expensive second-line antiretroviral drugs.

  11. Combining docking and molecular dynamic simulations in drug design.

    PubMed

    Alonso, Hernán; Bliznyuk, Andrey A; Gready, Jill E

    2006-09-01

    A rational approach is needed to maximize the chances of finding new drugs, and to exploit the opportunities of potential new drug targets emerging from genomic and proteomic initiatives, and from the large libraries of small compounds now readily available through combinatorial chemistry. Despite a shaky early history, computer-aided drug design techniques can now be effective in reducing costs and speeding up drug discovery. This happy outcome results from development of more accurate and reliable algorithms, use of more thoughtfully planned strategies to apply them, and greatly increased computer power to allow studies with the necessary reliability to be performed. Our review focuses on applications and protocols, with the main emphasis on critical analysis of recent studies where docking calculations and molecular dynamics (MD) simulations were combined to dock small molecules into protein receptors. We highlight successes to demonstrate what is possible now, but also point out drawbacks and future directions. The review is structured to lead the reader from the simpler to more compute-intensive methods. Thus, while inexpensive and fast docking algorithms can be used to scan large compound libraries and reduce their size, more accurate but expensive MD simulations can be applied when a few selected ligand candidates remain. MD simulations can be used: during the preparation of the protein receptor before docking, to optimize its structure and account for protein flexibility; for the refinement of docked complexes, to include solvent effects and account for induced fit; to calculate binding free energies, to provide an accurate ranking of the potential ligands; and in the latest developments, during the docking process itself to find the binding site and correctly dock the ligand a priori.

  12. The role of therapeutic drug monitoring in pediatric HIV/AIDS.

    PubMed

    Burger, David M

    2010-06-01

    International guidelines do not recommend therapeutic drug monitoring (TDM) of HIV-infected children as a routine measurement as part of medical management. There are, however, several clinical scenarios in which TDM may be indicated. Underdosing may be one of the major risks, especially in younger children. No randomized controlled clinical trials have been conducted to assess the added value of TDM in HIV-infected children, making recommendations for TDM in children with HIV/AIDS merely based on expert opinion. There is a need for more descriptive studies on the usefulness of TDM in HIV-infected children to convince pediatricians worldwide to let more children benefit from TDM.

  13. Proceedings of the ISEV symposium on “HIV, NeuroAIDS, drug abuse & EVs”

    PubMed Central

    Hu, Guoku; Witwer, Kenneth W.; Bond, Vincent C.; Haughey, Norman; Kashanchi, Fatah; Pulliam, Lynn; Buch, Shilpa

    2017-01-01

    ABSTRACT Extracellular vesicles (EVs) are globular, membrane bound nanovesicles (30–100 nm range) that are shed both during normal cellular functioning and under pathological conditions by most cell types. In recent years, there has been significant interest in the study of these vesicles as conduits for the delivery of information between cells from both analogous and disparate tissues. Their ability to carry specialised cargo including signalling mediators, proteins, messenger RNA and miRNAs characterises these vesicles as primary facilitators of cell-to-cell communication and regulation. EVs have also been demonstrated to play important roles in the field of cancer biology and metastasis. However, significant knowledge gaps exist in the role these vesicles play in the context of HIV infection and drug abuse. To foster discussion in this area a satellite symposium on “HIV, NeuroAIDS, Drug Abuse & EVs”, was held in conjunction with the annual meeting of the International Society for Extracellular Vesicles (ISEV) in Bethesda, in April 2015. Experts in HIV and drug abuse fields were invited to share their findings on the role of EVs in HIV-1 infection and drug addiction. Additional discussion included current areas of research in EV biology in HIV infection and drug abuse.

  14. Patents of bio-active compounds based on computer-aided drug discovery techniques.

    PubMed

    Prado-Prado, Francisco; Garcia-Mera, Xerardo; Rodriguez-Borges, Jose Enrique; Concu, Riccardo; Perez-Montoto, Lazaro Guillermo; Gonzalez-Diaz, Humberto; Duardo-Sanchez, Aliuska

    2013-01-01

    In recent times, there has been an increased use of Computer-Aided Drug Discovery (CADD) techniques in Medicinal Chemistry as auxiliary tools in drug discovery. Whilst the ultimate goal of Medicinal Chemistry research is for the discovery of new drug candidates, a secondary yet important outcome that results is in the creation of new computational tools. This process is often accompanied by a lack of understanding of the legal aspects related to software and model use, that is, the copyright protection of new medicinal chemistry software and software-mediated discovered products. In the center of picture, which lies in the frontiers of legal, chemistry, and biosciences, we found computational modeling-based drug discovery patents. This article aims to review prominent cases of patents of bio-active organic compounds that involved/protect also computational techniques. We put special emphasis on patents based on Quantitative Structure-Activity Relationships (QSAR) models but we include other techniques too. An overview of relevant international issues on drug patenting is also presented.

  15. 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…

  16. 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)

  17. 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.

  18. 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.

  19. [Drug design ideas and methods of Chinese herb prescriptions].

    PubMed

    Ren, Jun-guo; Liu, Jian-xun

    2015-09-01

    The new drug of Chinese herbal prescription, which is the best carrier for the syndrome differentiation and treatment of Chinese medicine and is the main form of the new drug research and development, plays a very important role in the new drug research and development. Although there are many sources of the prescriptions, whether it can become a new drug, the necessity, rationality and science of the prescriptions are the key to develop the new drug. In this article, aiming at the key issues in prescriptions design, the source, classification, composition design of new drug of Chinese herbal prescriptions are discussed, and provide a useful reference for research and development of new drugs.

  20. 23 CFR 636.104 - Does this part apply to all Federal-aid design-build projects?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ENGINEERING AND TRAFFIC OPERATIONS DESIGN-BUILD CONTRACTING General § 636.104 Does this part apply to all 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...

  1. Designing polymeric microparticulate drug delivery system for hydrophobic drug quercetin

    PubMed Central

    Hazra, Moumita; Dasgupta Mandal, Dalia; Mandal, Tamal; Bhuniya, Saikat; Ghosh, Mallika

    2015-01-01

    The aim of this study was to investigate pharmaceutical potentialities of a polymeric microparticulate drug delivery system for modulating the drug profile of poorly water-soluble quercetin. In this research work two cost effective polymers sodium alginate and chitosan were used for entrapping the model drug quercetin through ionic cross linking method. In vitro drug release, swelling index, drug entrapment efficiency, Fourier Transforms Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and Differential Scanning Calorimetric (DSC) studies were also done for physicochemical characterization of the formulations. Swelling index and drug release study were done at a pH of 1.2, 6.8 and 7.4 to evaluate the GI mimetic action which entails that the swelling and release of the all the Formulation1 (F1), Formulation2 (F2) and Formulation3 (F3) at pH 1.2 were minimal confirming the prevention of drug release in the acidic environment of stomach. Comparatively more sustained release was seen from the formulations F2 & F3 at pH 6.8 and pH 7.4 after 7 h of drug release profiling. Drug entrapment efficiency of the formulations shows in F1 (D:C:A = 2:5:30) was approximately 70% whereas the increase in chitosan concentration in F2 (D:C:A = 2:10:30) has shown an entrapment efficiency of 81%. But the comparative further increase of chitosan concentration in F3 (D:C:A = 2:15:30) has shown a entrapment of 80% which is not having any remarkable difference from F2. The FTIR analysis of drug, polymers and the formulations indicated the compatibility of the drug with the polymers. The smoothness of microspheres in F2 & F3 was confirmed by Scanning Electron Microscopy (SEM). However F1 microsphere has shown more irregular shape comparatively. The DSC studies indicated the absence of drug-polymer interaction in the microspheres. Our XRD studies have revealed that when pure drug exhibits crystalline structure with less dissolution profile

  2. 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.

  3. Public health the leading force of the Indonesian response to the HIV/AIDS crisis among people who inject drugs

    PubMed Central

    Mesquita, Fabio; Winarso, Inang; Atmosukarto, Ingrid I; Eka, Bambang; Nevendorff, Laura; Rahmah, Amala; Handoyo, Patri; Anastasia, Priscillia; Angela, Rosi

    2007-01-01

    Issue Indonesia has an explosive HIV/AIDS epidemic starting from the beginning of this century, and it is in process to build its response. Reported AIDS cases doubled from 2003 – 2004, and approximately 54% of these cases are in people who inject drugs. Setting Indonesia is the 4th largest country in population in the world, a predominantly Muslim country with strong views on drug users and people living with HIV/AIDS. Globally speaking, Indonesia has one of the most explosive epidemics in recent years. The project IHPCP (Indonesia HIV/AIDS Prevention and Care Project) is a joint support project (primarily AusAID-based) that works in partnership with the Government of Indonesia. IHPCP has been a key player of in the country's response, particularly pioneering NSP; stimulating and supporting methadone programs, and being key in promoting ARV for people who currently inject drugs. The project works via both the public health system and NGOs. Outcomes It is still early to measure the impact of current interventions; however, this paper describes the current status of Indonesia's response to the HIV/AIDS crisis among people who inject drugs, and analyses future challenges of the epidemic in Indonesia. PMID:17306033

  4. 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.

  5. Integrating structure-based and ligand-based approaches for computational drug design.

    PubMed

    Wilson, Gregory L; Lill, Markus A

    2011-04-01

    Methods utilized in computer-aided drug design can be classified into two major categories: structure based and ligand based, using information on the structure of the protein or on the biological and physicochemical properties of bound ligands, respectively. In recent years there has been a trend towards integrating these two methods in order to enhance the reliability and efficiency of computer-aided drug-design approaches by combining information from both the ligand and the protein. This trend resulted in a variety of methods that include: pseudoreceptor methods, pharmacophore methods, fingerprint methods and approaches integrating docking with similarity-based methods. In this article, we will describe the concepts behind each method and selected applications.

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2013-09-01

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

  8. 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

  9. Computational medicinal chemistry for rational drug design: Identification of novel chemical structures with potential anti-tuberculosis activity.

    PubMed

    Koseki, Yuji; Aoki, Shunsuke

    2014-01-01

    Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis and is a common infectious disease with high mortality and morbidity. The increasing prevalence of drug-resistant strains of TB presents a major public health problem. Due to the lack of effective drugs to treat these drug-resistant strains, the discovery or development of novel anti-TB drugs is important. Computer-aided drug design has become an established strategy for the identification of novel active chemicals through a combination of several drug design tools. In this review, we summarise the current chemotherapy for TB, describe attractive target proteins for the development of antibiotics against TB, and detail several computational drug design strategies that may contribute to the further identification of active chemicals for the treatment of not only TB but also other diseases.

  10. Fixed-point Design of the Lattice-reduction-aided Iterative Detection and Decoding Receiver for Coded MIMO Systems

    DTIC Science & Technology

    2011-01-01

    REPORT Fixed-point Design of theLattice-reduction-aided Iterative Detection andDecoding Receiver for Coded MIMO Systems 14. ABSTRACT 16. SECURITY...298 (Rev 8/98) Prescribed by ANSI Std. Z39.18 - Fixed-point Design of theLattice-reduction-aided Iterative Detection andDecoding Receiver for Coded ...important, this report illustrates the performance of coded LR aided detectors. 1 Fixed-point Design of the Lattice-reduction-aided Iterative Detection and

  11. 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.

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

    PubMed

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

    2014-09-01

    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.

  13. 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.

  14. 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.

  15. 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.

  16. Substance abuse treatment utilization among adults living with HIV/AIDS and alcohol or drug problems.

    PubMed

    Orwat, John; Saitz, Richard; Tompkins, Christopher P; Cheng, Debbie M; Dentato, Michael P; Samet, Jeffrey H

    2011-10-01

    This is a prospective cohort study to identify factors associated with receipt of substance abuse treatment (SAT) among adults with alcohol problems and HIV/AIDS. Data from the HIV Longitudinal Interrelationships of Viruses and Ethanol study were analyzed. Generalized estimating equation logistic regression models were fit to identify factors associated with any service utilization. An alcohol dependence diagnosis had a negative association with SAT (adjusted odds ratio [AOR] = 0.36, 95% confidence interval [95% CI] = 0.19-0.67), as did identifying sexual orientation other than heterosexual (AOR = 0.46, CI = 0.29-0.72) and having social supports that use alcohol/drugs (AOR = 0.62, CI = 0.45-0.83). Positive associations with SAT include presence of hepatitis C antibody (AOR = 3.37, CI = 2.24-5.06), physical or sexual abuse (AOR = 2.12, CI = 1.22-3.69), social supports that help with sobriety (AOR = 1.92, CI = 1.28-2.87), homelessness (AOR = 2.40, CI = 1.60-3.62), drug dependence diagnosis (AOR = 2.64, CI = 1.88-3.70), and clinically important depressive symptoms (AOR = 1.52, CI = 1.08-2.15). While reassuring that factors indicating need for SAT among people with HIV and alcohol problems (e.g., drug dependence) are associated with receipt, nonneed factors (e.g., sexual orientation, age) that should not decrease likelihood of receipt of treatment were identified.

  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 design of stripline ferrite junction circulators

    NASA Technical Reports Server (NTRS)

    Uzdy, Z.

    1980-01-01

    A general design procedure is presented for stripline Y-junction circulators employing solid dielectric between ground planes. The resonator design and impedance matching are derived in a form suitable for computer evaluation. The procedure is applicable to cases where either the circulator bandwidth or the ground plane spacing is specified. An experimental S-band switching circulator design illustrates the technique.

  19. Use of toxicological information in drug design.

    PubMed

    Matthews, E J; Benz, R D; Contrera, J F

    2000-12-01

    This paper is an extension of the keynote address and another talk at the Symposium on the Use of Toxiciological Information in Drug Design. The symposium was organized by American Chemical Society's Chemical Information Division at the 220th National Meeting of the American Chemical Society in Washington, DC, August 20-24, 2000. We outline an approach for meeting the scientific information needs of the U.S. Food and Drug Administration (FDA). Ready access to scientific information is critical to support safety-related regulatory decisions and is especially valuable in situations where available experimental information from in vivo/in vitro studies are inadequate or unavailable. This approach also has applications for lead selection in drug discovery. A pilot electronic toxicology/safety knowledge base and computational toxicology initiative is underway in the FDA Center for Drug Evaluation and Research (CDER) that may be a prototype for an FDA knowledge base. The objectives of this effort are: (i) to strengthen and broaden the scientific basis of regulatory decisions, (ii) to provide the Agency with an electronic scientific institutional memory, (iii) to create a scientific resource for regulatory and applied research, and (iv) to establish an internal Web-based support service that can provide decision support information for regulators that will facilitate the review process and improve consistency and uniformity. An essential component of this scientific knowledge base is the creation of a comprehensive electronic inventory of CDER-regulated substances that permit identification of clusters of substances having similar chemical, pharmacological or toxicological activities, and molecular structure/substructures. Furthermore, the inventory acts as a pointer and link to other databases and critical non-clinical and clinical pharmacology/toxicology studies and reviews in FDA archives. Clusters of related substances are identified through the use of: (i) an

  20. Designed multiple ligands: an emerging anti-HIV drug discovery paradigm.

    PubMed

    Zhan, Peng; Liu, Xinyong

    2009-01-01

    Currently, the effect of AIDS single-target chemotherapy is severely compromised by the quick emergence of resistant HIV strains. Highly active antiretroviral therapy (HAART) combines HIV reverse transcriptase inhibitors with protease inhibitors or integrase inhibitors, and successfully suppresses HIV viral load to an undetectable level, dramatically improving the life quality of AIDS patients. However, the benefits of this approach are often compromised by poor patient compliance. Recently, there has been a move toward multicomponent drugs whereby two or more agents are coformulated in a single tablet to make dosing regimes simpler and thereby to improve patient compliance, but there are significant risks involved in the development of multicomponent drugs. Designed multiple ligands (DMLs) therapy as an emerging anti-HIV drug discovery paradigm, using a single entity to inhibit multitargets could yield improved patient compliance, thus reducing the likelihood of drug resistance. The exploration of such multifunctional ligands has proven valuable for anti-HIV leads discovery. However, presently many multifunctional scaffolds were first discovered by serendipity or screening; rational design by combining existing monofunctional scaffolds remains an enormous challenge. A key issue in the design of multiple ligands is attaining a balanced activity at each target of interest while simultaneously achieving a wider selectivity and a suitable pharmacokinetic profile. This review of literature examples introduce numerous attractive lead compounds, capable of interfering with different stages of HIV infection and AIDS pathogenesis, which reveals trends and insights that might provide valuable clues for novel anti-HIV drug design and help medicinal chemists discover the next generation of multiple ligands.

  1. Drug design for protein kinases and phosphatases: flexible-receptor docking, binding affinity and specificity, and drug-binding kinetics.

    PubMed

    Wong, Chung F; Bairy, Sneha

    2013-01-01

    This article reviews some of our experiences on applying computational techniques to aid the design of drugs targeting protein kinases and phosphatases. It is not a comprehensive review. Rather, it focuses on several less explored approaches or ideas that we have experiences on. It reviews some recent improvements on the Poisson-Boltzmann/Surface Area model for calculating binding affinity and discusses ways to perform calculations that are more tolerant to statistical and systematic errors. Several new ways to incorporate protein flexibility in molecular docking and estimating binding affinity are also discussed. Its discussions also go beyond binding affinity to considering drug-binding kinetics, not only on investigating protein-ligand interactions in isolation, but also on accounting for upstream and downstream influences that can occur in cells, through kinetic modeling of cell signaling. This review also describes a quick molecular simulation method for understanding drug-binding kinetics at the molecular level, with the hope of generating guiding principles for designing drugs with the desired kinetic properties. Sources of drug-binding selectivity that appear obvious but often overlooked are also discussed.

  2. Methodology for Benefit Analysis of CAD/CAM (Computer-Aided Design/Computer-Aided Manufacturing) in USN Shipyards.

    DTIC Science & Technology

    1984-03-01

    D-Ri38 398 METHODOLOGY FOR BENEFIT ANALYSIS OF CAD/CAM / (COMPUTER-HIDED DESIGN/COMPUTER-AIDED MANUFACTURING) IN USN SHIPYARDS(U) NAVAL POSTGRADUATE...Monterey, California DT I ~" t • EB3 1984 THESIS METHODOLOGY FOR BENEFIT ANALYSIS OF CAD/CAM IN USN SHIPYARDS by Richard B. Grahlman March 1984 Thesis...REPORT & PERIOD COVERED Methodology for Benefit Analysis of CAD/CAM Mastrch 1984 i in UM Sipyads. PERFORMIANG ORG. REPORT NUM8ER 7- AUHOW11111 4

  3. 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.

  4. Active viral B hepatitis in parenteral drug abusers with acquired immune deficiency syndrome (AIDS).

    PubMed

    Leevy, C B; Nurse, H; Kapila, R

    1989-01-01

    Eighty-percent of 47 parenteral drug abusers with hepatomegaly and acquired immunodeficiency syndrome had HBV DNA in serum, although only 27% were HBsAg or "e" antigen-positive by polyclonal radioimmunoassay. Liver biopsies from each of 37 HBV DNA seropositive patients showed HBV DNA and were HBcAg-positive. The absence of positive HBsAg and "e" antigen in HBV DNA-positive patients was attributable to the presence of immune complexes; after in vitro dissociation of these complexes there was an increase in HBsAg from 24% to 86%, and of "e" antigen from 19% to 62%. These data indicate that actively replicating hepatitis B virus is common in patients with AIDS, and that precautions should be taken to prevent its dissemination. Therapy in these patients should address both human immunodeficiency and hepatitis B virus infections.

  5. 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

  6. Feline Immunodeficiency Virus Model for Designing HIV/AIDS Vaccines

    PubMed Central

    Yamamoto, Janet K.; Sanou, Missa P.; Abbott, Jeffrey R.; Coleman, James K.

    2013-01-01

    Feline immunodeficiency virus (FIV) discovered in 1986 is a lentivirus that causes AIDS in domestic cats. FIV is classified into five subtypes (A–E), and all subtypes and circulating intersubtype recombinants have been identified throughout the world. A commercial FIV vaccine, consisting of inactivated subtype-A and –D viruses (Fel-O-Vax FIV, Fort Dodge Animal Health), was released in the United States in 2002. The United States Department of Agriculture approved the commercial release of Fel-O-Vax FIV based on two efficacy trials using 105 laboratory cats and a major safety trial performed on 689 pet cats. The prototype and commercial FIV vaccines had broad prophylactic efficacy against global FIV subtypes and circulating intersubtype recombinants. The mechanisms of cross-subtype efficacy are attributed to FIV-specific T-cell immunity. Findings from these studies are being used to define the prophylactic epitopes needed for an HIV-1 vaccine for humans. PMID:20210778

  7. An Educational Design To Teach Drug Information Across the Curriculum.

    ERIC Educational Resources Information Center

    Gora-Harper, Mary Lea; Brandt, Barbara F.

    1997-01-01

    Describes design and implementation of a model for teaching drug information across the pharmacy curriculum. Program components include teaching/reinforcing drug information knowledge and skills; outlining practice-based outcomes for drug information; and impressing on students that such skills are routinely needed in pharmacy practice. Early…

  8. Formal design methods for reliable computer-aided diagnosis: a review.

    PubMed

    Faust, Oliver; Acharya, U Rajendra; Tamura, Toshiyo

    2012-01-01

    Physiological signals, medical images, and biosystems can be used to access the health of a subject and they can support clinicians by improving the diagnosis for treatment purposes. Computer-aided diagnosis (CAD) in healthcare applications can help in automated decision making, visualization and extraction of hidden complex features to aid in the clinical diagnosis. These CAD systems focus on improving the quality of patient care with a minimum of fault due to device failures. In this paper, we argue that a formal and model driven design methodology can lead to systems which meet this requirement. Modeling is not new to CAD, but modeling for systems design is less explored. Therefore, we discuss selected systems design techniques and provide a more concrete design example on computer-aided diagnosis and automated decision making.

  9. Computer-aided methods in bespoke breast prosthesis design and fabrication.

    PubMed

    Eggbeer, D; Evans, P

    2011-01-01

    This case study presents a method of utilizing computer-aided design technologies to provide bespoke, external breast prostheses. The technique is illustrated through a case study of a mastectomy patient. Photogrammetry methods were used to capture the breast form when supported by a brassiere and the unsupported breast and defect side. Computer-aided design techniques were used to generate a digital prosthesis based upon the supported breast shape and with a fitting surface that matched the defect side. Furthermore, a two-part mould was designed and fabricated using rapid prototyping methods. A colour-matched prosthesis was then fabricated in a gel-based, platinum-cured silicone.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Computer-Aided Design of Fragment Mixtures for NMR-Based Screening

    PubMed Central

    Arroyo, Xavier; Goldflam, Michael; Feliz, Miguel; Belda, Ignasi; Giralt, Ernest

    2013-01-01

    Fragment-based drug discovery is widely applied both in industrial and in academic screening programs. Several screening techniques rely on NMR to detect binding of a fragment to a target. NMR-based methods are among the most sensitive techniques and have the further advantage of yielding a low rate of false positives and negatives. However, NMR is intrinsically slower than other screening techniques; thus, to increase throughput in NMR-based screening, researchers often assay mixtures of fragments, rather than single fragments. Herein we present a fast and straightforward computer-aided method to design mixtures of fragments taken from a library that have minimized NMR signal overlap. This approach enables direct identification of one or several active fragments without the need for deconvolution. Our approach entails encoding of NMR spectra into a computer-readable format that we call a fingerprint, and minimizing the global signal overlap through a Monte Carlo algorithm. The scoring function used favors a homogenous distribution of the global signal overlap. The method does not require additional experimental work: the only data required are NMR spectra, which are generally recorded for each compound as a quality control measure before its insertion into the library. PMID:23516512

  15. A critical overview of analytical aids of design

    SciTech Connect

    Esat, I.

    1996-12-31

    The paper discusses effectiveness of some of the most important analytical tools of design in terms of their relationship to the design integration. The paper finally concludes that the level of integration remains rather superficial and success is only in certain areas relating to the downstream aspects of design. The degree of integration, particularly in the early stages of design activity, such as conceptualization remains very little. More importantly the paper points to the signs of stagnation, despite of phenomenal progress in every aspects of science, in many areas of science and engineering. The main cause of the stagnation is the curse of dimensionality and the complexity. The complexity now effecting every aspects of science and engineering. From the continuum mechanics to scheduling problems, ineffectiveness of the analytical tools of science and engineering becoming too obvious.

  16. 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...

  17. 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)

  18. Organic carbamates in drug design and medicinal chemistry.

    PubMed

    Ghosh, Arun K; Brindisi, Margherita

    2015-04-09

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

  19. 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.

  20. 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

  1. Application of 3D-QSAR techniques in anti-HIV-1 drug design--an overview.

    PubMed

    Debnath, Asim Kumar

    2005-01-01

    Despite the availability of several classes of drugs against acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus type 1(HIV-1), this deadly disease showing very little sign of containment, especially in Sub-Saharan Africa and South-East Asia. More than 20 million people died since the first diagnosis of AIDS more than twenty years ago and almost 40 million people are currently living with HIV/AIDS. Structure-based drug design effort was immensely successful in identifying several drugs that are currently available for the treatment of HIV-1. Many applications have been reported on the use of quantitative structure-activity relationship (QSAR) studies to understand the drug-receptor interactions and help in the design of more effective analogs. Extensive application was also reported on the application of 3D-QSAR techniques, such as, Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Analysis (CoMSIA), pharmacophore generation using Catalyst/HypoGen, free-energy binding analysis, GRID/GOLPE, HINT-based techniques, etc. in anti-HIV-1 drug discovery programs in academia and industry. We have attempted to put together a comprehensive overview on the 3D-QSAR applications in anti-HIV-1 drug design reported in the literature during the last decade.

  2. 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

  3. Using simulation to aid trial design: Ring-vaccination trials

    PubMed Central

    Hitchings, Matt David Thomas; Grais, Rebecca Freeman

    2017-01-01

    Background The 2014–6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination. Methods and findings We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design. Conclusions Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring

  4. Computer aided optimal design of compressed air energy storage systems

    NASA Astrophysics Data System (ADS)

    Ahrens, F. W.; Sharma, A.; Ragsdell, K. M.

    1980-07-01

    An automated procedure for the design of Compressed Air Energy Storage (CAES) systems is presented. The procedure relies upon modern nonlinear programming algorithms, decomposition theory, and numerical models of the various system components. Two modern optimization methods are employed; BIAS, a Method of Multipliers code and OPT, a Generalized Reduced Gradient code. The procedure is demonstrated by the design of a CAES facility employing the Media, Illinois Galesville aquifer as the reservoir. The methods employed produced significant reduction in capital and operating cost, and in number of aquifer wells required.

  5. 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

  6. Successes in drug discovery and design.

    PubMed

    2004-04-01

    The Society for Medicines Research (SMR) held a one-day meeting on case histories in drug discovery on December 4, 2003, at the National Heart and Lung Institute in London. These meetings have been organized by the SMR biannually for many years, and this latest meeting proved extremely popular, attracting a capacity audience of more than 130 registrants. The purpose of these meetings is educational; they allow those interested in drug discovery to hear key learnings from recent successful drug discovery programs. There was no overall linking theme between the talks, other than each success story has led to the introduction of a new and improved product of therapeutic use. The drug discovery stories covered in the meeting were extremely varied and, put together, they emphasized that each successful story is unique and special. This meeting is also special for the SMR because it presents the "SMR Award for Drug Discovery" in recognition of outstanding achievement and contribution in the area. It should be remembered that drug discovery is an extremely risky business and an extremely costly and complicated process in which the success rate is, at best, low.

  7. 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.

  8. 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

  9. Special Technology Area Review on Computer Aided Design

    DTIC Science & Technology

    1993-03-01

    develop MHDL, AHDL , etc., not only to provide a common modeling language but also to support a robust design environment. This would include language...tools are critical. Analog synthesis requirements must be reflected in VHDL and AHDL (Analog Hardware Description Language) standards. The tools should

  10. Computer aided design of jet engine test cell exhaust systems

    SciTech Connect

    Collings, D.

    1982-01-01

    A computerized design procedure that provides a multi-directional analysis of available data is a proven method of developing accurate cost models and performing system trade-offs. The application to the engineering of exhaust silencing systems for jet engine test cells is discused.

  11. Design Principles for Computer-Aided Vocabulary Learning.

    ERIC Educational Resources Information Center

    Goodfellow, Robin

    1994-01-01

    Presents six principles for the design of adaptive computer-assisted language learning (CALL) programs for vocabulary that incorporate a theory describing quality in the learning outcome and linking it to the learner's approach. Highlights include interactivity; general architecture of a software system; and diagnosis and modification. (Contains…

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

    SciTech Connect

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

    2016-02-17

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

  13. Recent advances in the design and development of soft drugs.

    PubMed

    Buchwald, P; Bodor, N

    2014-06-01

    This paper summarizes recent developments in the field of soft drug development as collected and reviewed for the 9th Retrometabolism-Based Drug Design and Targeting Conference. Soft drugs are still often confused with prodrugs because they both require metabolic transformations; however, they are conceptual opposites: whereas, prodrugs are pharmacologically inactive and are converted by a predictable mechanism to the active drug, soft drugs are active therapeutic agents as such and are designed to undergo a predictable and controllable metabolic deactivation after exerting their desired therapeutic effect. Several rationally designed soft drug examples including clinically approved ones (e.g., clevidipine, esmolol, landiolol, loteprednol etabonate, and remifentanil) as well as others that have reached clinical investigations within different therapeutic areas (e.g., budiodarone, naronapride, remimazolam, tecarfarine) are briefly summarized. Anesthesiology, which requires a high degree of pharmacologic control during the surgical procedure to maintain the anesthetic state together with a quick return to responsiveness at the end of this procedure, is a particularly well-suited area for soft drug development. Several new initiatives (e.g., MOC-etomidate, AZD3043) are focused in this area; they are also briefly reviewed. Finally, just as there are many 'accidental' prodrugs, there are 'accidental' soft drugs too: i.e., therapeutics that were not intentionally designed to be soft drugs, but turned out to be essentially soft drugs. Some examples, such as articaine or methylphenidate, are briefly reviewed.

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

    PubMed

    Verma, Saroj; Prabhakar, Yenamandra S

    2015-01-01

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

  15. Types of Hearing Aids

    MedlinePlus

    ... Devices Consumer Products Hearing Aids Types of Hearing Aids Share Tweet Linkedin Pin it More sharing options ... some features for hearing aids? What are hearing aids? Hearing aids are sound-amplifying devices designed to ...

  16. 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.

  17. Fracture resistance of computer-aided design/computer-aided manufacturing-generated composite resin-based molar crowns.

    PubMed

    Harada, Akio; Nakamura, Keisuke; Kanno, Taro; Inagaki, Ryoichi; Örtengren, Ulf; Niwano, Yoshimi; Sasaki, Keiichi; Egusa, Hiroshi

    2015-04-01

    The aim of this study was to investigate whether different fabrication processes, such as the computer-aided design/computer-aided manufacturing (CAD/CAM) system or the manual build-up technique, affect the fracture resistance of composite resin-based crowns. Lava Ultimate (LU), Estenia C&B (EC&B), and lithium disilicate glass-ceramic IPS e.max press (EMP) were used. Four types of molar crowns were fabricated: CAD/CAM-generated composite resin-based crowns (LU crowns); manually built-up monolayer composite resin-based crowns (EC&B-monolayer crowns); manually built-up layered composite resin-based crowns (EC&B-layered crowns); and EMP crowns. Each type of crown was cemented to dies and the fracture resistance was tested. EC&B-layered crowns showed significantly lower fracture resistance compared with LU and EMP crowns, although there was no significant difference in flexural strength or fracture toughness between LU and EC&B materials. Micro-computed tomography and fractographic analysis showed that decreased strength probably resulted from internal voids in the EC&B-layered crowns introduced by the layering process. There was no significant difference in fracture resistance among LU, EC&B-monolayer, and EMP crowns. Both types of composite resin-based crowns showed fracture loads of >2000 N, which is higher than the molar bite force. Therefore, CAD/CAM-generated crowns, without internal defects, may be applied to molar regions with sufficient fracture resistance.

  18. Experience gained at ZAO Ural Turbine Works with the use of computer-aided design systems

    NASA Astrophysics Data System (ADS)

    Kortenko, V. V.; Valamin, A. E.; Shanturov, D. N.; Sokolov, E. V.; Toibich, S. V.; Glushchenko, A. N.

    2008-08-01

    The results of work accomplished in the field of computer-aided design at ZAO Ural Turbine Works (UTZ) are presented. A concept is described following which the tasks for a specialist’s workstations being developed at the UTZ are solved. Results from solution of problems with the use of modern numerical simulation computer programs for analyzing gas dynamic processes, casting, welding, and strength of complex structures are given. An example is given to show efficient use of a computer-aided design system for shifting an enterprise to a modern level of automation.

  19. 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.

  20. 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.

  1. 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

  2. Intelligent Embedded Instruction for Computer-Aided Design (CAD) systems

    DTIC Science & Technology

    1988-10-01

    8217 convenience and according to their individual learning preferences. This benefit is extremely valuable for adult professionals whose needs may be highly...solving problems. Adult designers tend to develop their own personal ways of using CAD software which can optimize a system’s use. This ability has been...average age for subjects with more than 1 year of computer experience was 34 whereas those with less than 2 months of experience averaged 41 years old

  3. Design, fabrication, and testing of contact-aided compliant cellular mechanisms with curved walls

    NASA Astrophysics Data System (ADS)

    Cirone, Samantha A.; Hayes, Gregory R.; Babcox, Brian L.; Frecker, Mary; Adair, James H.; Lesieutre, George A.

    2011-03-01

    Contact-Aided Compliant Cellular Mechanisms (C3M) are compliant cellular structures with integrated contact mechanisms. The focus of the paper is on the design, fabrication, and testing of C3M with curved walls for high strain applications. It is shown that global strains were increased by replacing straight walls with curved walls in the traditional honeycomb structure, while the addition of contact mechanisms increased cell performance via stress relief in some cases. Furthermore, curved walls are beneficial for fabrication at the meso-scale. The basic curved honeycomb cell geometry is defined by a set of variables. These variables were optimized using Matlab and finite element analysis to find the best non-contact and contact-aided curved cell geometries as well as the cell geometry that provides the greatest stress relief. Currently, the most effective contact-aided curved honeycomb cell can withstand global strains approximately 160% greater than the most effective contact-aided, non-curved cell. Four different designs were fabricated via the Lost Mold-Rapid Infiltration Forming (LM-RIF) process. An array of the contact-aided optimized curved cell was then mechanically tested using a custom designed test rig, and the results were found to have a higher modulus of elasticity and lower global strain than the predictions. Despite these discrepancies, a high-strength highstrain cellular structure was developed, for potential use in morphing aircraft applications.

  4. 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.

  5. A Study of Computer-Aided Geometric Optical Design.

    DTIC Science & Technology

    1982-10-01

    WAHLSTEDT OCT B2 AFIT/GEP/PH/82D-24 UNCLASSIFIED F /’G 9/2 N smhohmohholi EohhhhhhhhhhhE 1111.2 1 .6 mmiima __’___ MICROCOPY RESOLUTION TEST CHART NATIONAL...The irting point () f the desigri was a Questar 3 inch telescope.. Avidj tional optic:l elements were added and " the design impoved until the desirF...The P|WI? J ) f e the lens is defined as the index of refractioni at ,ither focal point divided by the respective focal length. The power of the lens

  6. A Functional Level Preprocessor for Computer Aided Digital Design.

    DTIC Science & Technology

    1980-12-01

    the parsing of ucer input, is based on that for the computer language, PASCAL [J2,1J. The procedure is tle author’s original design Each line of input...NIKLAUS WIR~iN. PASCAL -USER:I MANUAL AmD REPORT. NEW YORK, NY: SPRINGER-VERLAG 1978 Li LANCAST17R, DOIN. CMOS CoORBOLK(A. IND)IANAPOLIS, IND): HOWAI(D...34flGS 0151, OtTAll me:;genera ted by SISL, duri -ne iti; last run. Each message is of the foriiat: SutiWur Uk ;L ATLNG M1:SSA(;lE-, )’URIAT NUMBELR, and

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

    PubMed

    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.

  8. 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.

  9. 21 CFR 516.23 - Timing of requests for MUMS-drug designation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-drug designation. A sponsor may request MUMS-drug designation at any time in the drug development... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Timing of requests for MUMS-drug designation. 516.23 Section 516.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  10. 21 CFR 516.23 - Timing of requests for MUMS-drug designation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-drug designation. A sponsor may request MUMS-drug designation at any time in the drug development... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Timing of requests for MUMS-drug designation. 516.23 Section 516.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  11. 21 CFR 516.23 - Timing of requests for MUMS-drug designation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-drug designation. A sponsor may request MUMS-drug designation at any time in the drug development... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Timing of requests for MUMS-drug designation. 516.23 Section 516.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  12. 21 CFR 516.23 - Timing of requests for MUMS-drug designation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-drug designation. A sponsor may request MUMS-drug designation at any time in the drug development... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Timing of requests for MUMS-drug designation. 516.23 Section 516.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  13. 21 CFR 516.23 - Timing of requests for MUMS-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-drug designation. A sponsor may request MUMS-drug designation at any time in the drug development... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Timing of requests for MUMS-drug designation. 516.23 Section 516.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  14. Racial Differences in HIV/AIDS Discussion Strategies and Sexual Risk Behaviors among Drug Abusing Female Criminal Offenders

    PubMed Central

    Oser, Carrie B.; Havens, Jennifer R.; Mooney, Jennifer L.; Staton-Tindall, Michele; Knudsen, Hannah K.; Duvall, Jamieson L.; Leukefeld, Carl G.

    2009-01-01

    African American female inmates are disproportionately affected by the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS), with heterosexual contact as the primary mode of transmission. This could be the result of racial differences in the strategies used by women to persuade a potential sexual partner to discuss AIDS and engage in condom use. Data were collected from 336 female inmates in three correctional institutions as part of the Reducing Risky Relationships for HIV (RRR-HIV) protocol within the Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) cooperative agreement. Bivariate analyses indicated that African American drug using women were more likely than Whites to use the rational, withdrawal, and persistence approaches to discuss AIDS with an intimate sexual partner. Negative binomial regression models were used to identify which interpersonal discussion strategies were significant correlates of the number of the times White participants and African American participants had unprotected vaginal sex in the 30 days prior to incarceration. Results from the multivariate model indicate that White women who are more likely to use the rational discussion strategy were 15% less likely to engage in vaginal sex without a condom; however, these findings were not replicated in the African American sample. Findings add to the literature on racial differences in HIV/AIDS discussion strategies and sexual risk behaviors among drug abusing female criminal offenders. PMID:19283952

  15. Computer-Aided Design of RNA Origami Structures.

    PubMed

    Sparvath, Steffen L; Geary, Cody W; Andersen, Ebbe S

    2017-01-01

    RNA nanostructures can be used as scaffolds to organize, combine, and control molecular functionalities, with great potential for applications in nanomedicine and synthetic biology. The single-stranded RNA origami method allows RNA nanostructures to be folded as they are transcribed by the RNA polymerase. RNA origami structures provide a stable framework that can be decorated with functional RNA elements such as riboswitches, ribozymes, interaction sites, and aptamers for binding small molecules or protein targets. The rich library of RNA structural and functional elements combined with the possibility to attach proteins through aptamer-based binding creates virtually limitless possibilities for constructing advanced RNA-based nanodevices.In this chapter we provide a detailed protocol for the single-stranded RNA origami design method using a simple 2-helix tall structure as an example. The first step involves 3D modeling of a double-crossover between two RNA double helices, followed by decoration with tertiary motifs. The second step deals with the construction of a 2D blueprint describing the secondary structure and sequence constraints that serves as the input for computer programs. In the third step, computer programs are used to design RNA sequences that are compatible with the structure, and the resulting outputs are evaluated and converted into DNA sequences to order.

  16. Computer-aided design and three-dimensional printing in the manufacturing of an ocular prosthesis.

    PubMed

    Ruiters, Sébastien; Sun, Yi; de Jong, Stéphan; Politis, Constantinus; Mombaerts, Ilse

    2016-04-27

    Restoring the facial appearance in acquired anophthalmos entails precision fitting of a customised ocular prosthesis. The fabrication is an artisanal process, and is primarily based on an impression of the anophthalmic cavity. This is usually achieved by the impression-moulding method, which, however, may introduce errors, resulting in a poorly fitted prosthesis. We developed a new method in the manufacturing of a customised ocular prosthesis based on computer-aided design and computer-aided manufacturing. An ocular prosthesis, based on a three-dimensional (3D) printed impression-free mould of the anophthalmic cavity, was successfully fitted in a 68-year-old male. To the best of our knowledge, this is the first case of a customised ocular prosthesis designed with the aid of 3D printing.

  17. The Design of a Project to Assess Bilateral Versus Unilateral Hearing Aid Fitting

    PubMed Central

    Arlinger, Stig; Gatehouse, Stuart; Kiessling, Jürgen; Naylor, Graham; Verschuure, Hans; Wouters, Jan

    2008-01-01

    Binaural hearing provides advantages over monaural in several ways, particularly in difficult listening situations. For a person with bilateral hearing loss, the bilateral fitting of hearing aids thus seems like a natural choice. However, surprisingly few studies have been reported in which the additional benefit of bilateral versus unilateral hearing aid use has been investigated based on real-life experiences. Therefore, a project has been designed to address this issue and to find tools to identify people for whom the drawbacks would outweigh the advantages of bilateral fitting. A project following this design is likely to provide reliable evidence concerning differences in benefit between unilateral and bilateral fitting of hearing aids by evaluating correlations between entrance data and outcome measures and final preferences. PMID:18567594

  18. Structure-based drug design to overcome drug resistance: challenges and opportunities.

    PubMed

    Ferreira, Rafaela S; Andricopulo, Adriano D

    2014-01-01

    Drug resistance is a common concern for the development of novel antiviral, antimicrobial and anticancer therapies. To overcome this problem, several strategies have been developed, many of which involving the theme of this review, the use of structure-based drug design (SBDD) approaches. These include the successful design of new compounds that target resistant mutant proteins, as well as the development of drugs that target multiple proteins involved in specific biochemical pathways. Finally, drug resistance can also be considered in the early stages of drug discovery, through the use of strategies to delay the development of resistance. The purpose of this brief review is to underline the usefulness of SBDD approaches based on case studies, highlighting present challenges and opportunities in drug design.

  19. 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.

  20. Hemozoin Formation as a Target for Antimalarial Drug Design

    DTIC Science & Technology

    2005-02-01

    AD Award Number: DAMD17-03-1-0030 TITLE: Hemozoin Formation as a Target for Antimalarial Drug Design PRINCIPAL INVESTIGATOR: Michael K. Riscoe, Ph.D...Formation as a Target for Antimalarial Drug Design DAMD17-03-1-0030 6. A UTHOR(S) Michael K. Riscoe, Ph.D. 7. PERFORMING ORGANIZA TION NAME(S) AND ADDRESS...Report: by Principal Investigator - Michael K. Riscoe, Ph.D. DAMD1 7-03-1-0030: "Hemozoin Formation as a Target for Antimalarial Drug Design " INTRODUCTION

  1. Ineffectiveness of AIDS education and HIV antibody testing in reducing high-risk behaviors among injection drug users.

    PubMed Central

    Calsyn, D A; Saxon, A J; Freeman, G; Whittaker, S

    1992-01-01

    The effectiveness of education in reducing high-risk human immunodeficiency virus (HIV) transmission behaviors was examined in 313 injection drug users. Involvement in high-risk behaviors was assessed via structured interview at study entry and 4 months following the intervention. Subjects were randomly assigned to (1) AIDS education, (2) AIDS education with optional HIV antibody testing, or (3) a wait list. The sample as a whole decreased its involvement in high-risk behaviors, but there were no significant differences as a function of experimental group assignment. PMID:1546776

  2. 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.

  3. 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.

  4. Drug resistance marker-aided genome shuffling to improve acetic acid tolerance in Saccharomyces cerevisiae.

    PubMed

    Zheng, Dao-Qiong; Wu, Xue-Chang; Wang, Pin-Mei; Chi, Xiao-Qin; Tao, Xiang-Lin; Li, Ping; Jiang, Xin-Hang; Zhao, Yu-Hua

    2011-03-01

    Acetic acid existing in a culture medium is one of the most limiting constraints in yeast growth and viability during ethanol fermentation. To improve acetic acid tolerance in Saccharomyces cerevisiae strains, a drug resistance marker-aided genome shuffling approach with higher screen efficiency of shuffled mutants was developed in this work. Through two rounds of genome shuffling of ultraviolet mutants derived from the original strain 308, we obtained a shuffled strain YZ2, which shows significantly faster growth and higher cell viability under acetic acid stress. Ethanol production of YZ2 (within 60 h) was 21.6% higher than that of 308 when 0.5% (v/v) acetic acid was added to fermentation medium. Membrane integrity, higher in vivo activity of the H+-ATPase, and lower oxidative damage after acetic acid treatment are the possible reasons for the acetic acid-tolerance phenotype of YZ2. These results indicated that this novel genome shuffling approach is powerful to rapidly improve the complex traits of industrial yeast strains.

  5. 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.

  6. 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…

  7. 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…

  8. Technology and Jobs: Computer-Aided Design. Numerical-Control Machine-Tool Operators. Office Automation.

    ERIC Educational Resources Information Center

    Stanton, Michael; And Others

    1985-01-01

    Three reports on the effects of high technology on the nature of work include (1) Stanton on applications and implications of computer-aided design for engineers, drafters, and architects; (2) Nardone on the outlook and training of numerical-control machine tool operators; and (3) Austin and Drake on the future of clerical occupations in automated…

  9. 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…

  10. 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…

  11. 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…

  12. 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.

  13. 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.

  14. 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.

  15. 'Surprise' Designer Drugs Detected in NYC Hair Samples

    MedlinePlus

    ... 164500.html 'Surprise' Designer Drugs Detected in NYC Hair Samples Stimulant-taking party-goers don't always ... in 2015. For the new study, researchers collected hair samples from 80 young adults outside nightclubs and ...

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. A novel application of computer-aided design and manufacturing for reduction cranioplasty.

    PubMed

    Dorafshar, Amir; Fisher, Mark; Borsuk, Daniel; Fishman, Elliot; Ahn, Edward

    2014-01-01

    Macrocephaly is a rare presentation of untreated hydrocephalus. In cases where medical management has failed, macrocephaly can be managed with reduction cranioplasty. Traditionally, reduction cranioplasty is highly dependent on intraoperative tailoring of bone segments to obtain the best possible result and involves high risks of associated severe blood loss and mortality. In this clinical report, we describe a patient with hydrocephalus macrocephaly treated with reduction cranioplasty with the innovative use of computer-aided design and manufacturing to reduce intraoperative risks and improve efficiency. We used computer-aided design to plan osteotomy sites and the final positioning of bone segments. We also utilized computer-aided manufacturing to produce cutting guides, positioning guides, and models to increase precision and improve the final positioning of the cranium. Computer-aided design and manufacturing technology has enabled a shift of the planning burden of complicated craniofacial reconstructions from the intraoperative to the preoperative phase. With a completed plan and premade guides and models, it is possible to minimize the risks, improve efficiency, and obtain a precise, aesthetic result.

  5. 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

  6. 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

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

    PubMed

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

    2014-01-01

    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-induced pancreatitis

  8. Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

    PubMed Central

    Furlong, Michael; Seong, Jae Young

    2017-01-01

    Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples. PMID:28035082

  9. 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

  10. Membrane-Protein Crystallography and Potentiality for Drug Design

    NASA Astrophysics Data System (ADS)

    Yamashita, Atsuko

    Structure-based drug design for membrane proteins is far behind that for soluble proteins due to difficulty in crystallographic structure determination, despite the fact that about 60% of FDA-approved drugs target membrane proteins located at the cell surface. Stable homologs for a membrane protein of interest, such as prokaryotic neurotransmitter transporter homolog LeuT, might enable cooperative analyses by crystallography and functional assays, provide useful information for functional mechanisms, and thus serve as important probes for drug design based on mechanisms as well as structures.

  11. [Computational chemistry in structure-based drug design].

    PubMed

    Cao, Ran; Li, Wei; Sun, Han-Zi; Zhou, Yu; Huang, Niu

    2013-07-01

    Today, the understanding of the sequence and structure of biologically relevant targets is growing rapidly and researchers from many disciplines, physics and computational science in particular, are making significant contributions to modern biology and drug discovery. However, it remains challenging to rationally design small molecular ligands with desired biological characteristics based on the structural information of the drug targets, which demands more accurate calculation of ligand binding free-energy. With the rapid advances in computer power and extensive efforts in algorithm development, physics-based computational chemistry approaches have played more important roles in structure-based drug design. Here we reviewed the newly developed computational chemistry methods in structure-based drug design as well as the elegant applications, including binding-site druggability assessment, large scale virtual screening of chemical database, and lead compound optimization. Importantly, here we address the current bottlenecks and propose practical solutions.

  12. Impact of the AIDS epidemic on morbidity and mortality among intravenous drug users in a New York City methadone maintenance program.

    PubMed

    Selwyn, P A; Hartel, D; Wasserman, W; Drucker, E

    1989-10-01

    To examine the impact of the AIDS epidemic on morbidity and mortality in a defined population of intravenous drug users, we analyzed overall and cause-specific death rates, AIDS incidence, and acute medical hospitalizations among patients in a long-term methadone maintenance program in New York City for the years 1984 through 1987 (midyear population for each year 828 to 891; demographic characteristics did not differ). The number of deaths while in treatment increased from 11 (13.3/1000) in 1984 to 39 (44.2/1000) in 1987. Deaths from AIDS increased from 3.6/1000 to 14.7/1000, deaths due to bacterial pneumonia/sepsis from 3.6/1000 to 13.6/1000; deaths from cirrhosis, drug overdose, trauma, and other causes remained relatively stable. AIDS incidence rose from six cases/1000 in 1984 to 20.4.1000 in 1987. Hospitalizations for AIDS, pneumonia, tuberculosis, and endocarditis/sepsis increased from 84.9/1000 in 1986 to 144.8/1000 in 1987. These data suggest that the AIDS epidemic has had a profound effect on patterns of morbidity and mortality among intravenous drug users in this methadone program population. Drug treatment programs may be important sites for targeting clinical services for drug users with AIDS, although the increasing burden of AIDS-related disease will require expansion of existing funding and treatment resources.

  13. 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

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

    NASA Astrophysics Data System (ADS)

    Santos, Ricardo N.; Andricopulo, Adriano D.

    2013-08-01

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

  15. 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

  16. 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.

  17. 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

  18. 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

    2015-12-07

    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.

  19. Multi-Input/Multi-Output Designated Eigenstructure (MODES): A Computer-Aided Control System Design Program.

    DTIC Science & Technology

    1987-03-01

    must. introduce some tools. The first of these is known as Newton’s Formulas ( Uspensky , 1948: 261). oA 4-32 ’ */ Newton’s Formulas relate the...Academic Press, Inc., 1976. Uspensky , J.V. Theory of Equations. New York: McGraw- Hill Book Company, 1948. Walker, Robert A., et al. "Computer-Aided

  20. 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

  1. Recent advances in drugs and prodrugs design of chitosan.

    PubMed

    Vinsova, J; Vavrikova, E

    2008-01-01

    The aim of this review is to outline the recent advances in chitosan molecular modeling, especially its usage as a prodrug or drug in a field of antibacterial, anticarcinogenic and antioxidant activity. Polymeric materials like peptides, polysaccharides and other natural products have recently attracted attention as biodegradabile drug carriers. They can optimize clinical drug application, minimize the undesirable drug properties and improve drug efficiency. They are used for the slow release of effective components as depot forms, to improve membrane permeability, solubility and site-specific targeting. Chitosan is such a prospective cationic polysaccharide which has shown number of functions in many fields, including bio medicinal, pharmaceutical, preservative, microbial and others. This article discusses the structure characteristics of chitosan, a number of factors such as degree of polymerization, level of deacetylation, types of quarternisation, installation of various hydrophilic substituents, metal complexation, and combination with other active agents. Biodegradable, non-toxic and non-allergenic nature of chitosan encourages its potential use as a carrier for drug delivery systems in all above mentioned targets. The use of chitosan prodrug conjugates is aimed at the site-specific transport to the target cells use, for example, a spacer tetrapeptide Gly-Phe-Leu-Gly, promotion of drug incorporation into cells via endocytosis, hybridization or synergism of two types of drugs or a drug with a bioactive carrier. The design of chitosan macromolecule prodrugs is also discussed.

  2. 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.

  3. 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.

  4. AIDS and society.

    PubMed

    Singh, N K

    1991-08-01

    Noting the hysteria caused by an outbreak of AIDS among intravenous drug users in the state of Manipur, India, the author discusses the social and emotional aspects of the epidemic. Local media has been Manipur's main source of information concerning the outbreak, but this information has often been misleading and has served to stir up fear and hatred of HIV carriers. Many have even begun talking about an Isolation Centre. The author, the director of a drug rehabilitation center, relates his experiences in counseling 50 intravenous drug users on the subject of AIDS. He discovered that the group had very poor knowledge about the disease. When told about AIDS, they became alarmed at the possibility of dying. 1/2 of the group swore to take revenge on those who had introduced them to drugs, but the other 1/2 showed a more positive attitude, saying that they would like to help other drug addicts. The author also describes the case history of a patient who had succeeded in staying off of drugs for 8 months. HIV screening, however, revealed that the young man was seropositive. Somehow, a local newspaper got a hold of this information and published his name as a seropositive along with the names of others. Distraught by this, the young man returned to drugs. The author stresses that revealing the names of HIV carriers serves no social purpose, and in fact, only makes the problem worse. He recommends the following for dealing with the outbreak of AIDS: 1) intensive public health education on AIDS with the aim or removing unwarranted fears; 2) education to prevent drug addiction; 3) counselling to parents of drug addicts; and 4) the establishment of Seropositive Anonymous, an organization designed to help carriers deal with their problems.

  5. A Computer-Aided Approach for Designing Edge-Slot Waveguide Arrays

    NASA Technical Reports Server (NTRS)

    Gosselin, Renee Brian

    2003-01-01

    Traditional techniques for designing resonant edge-slot waveguide arrays have required an iterative trial-and-error process of measuring slot data from several prototypes. Since very little meaningful data has been published, this technology remains relatively immature and prohibitive for many smaller programs that could benefit from some advantages this antenna has to offer. A new Computer-Aided Design technique for designing resonant edge-slot waveguide arrays was used to successfuliy design such an X-band radiometer antenna for the NASA Light Rainfall Radiometer (LRR) instrument. Having the ability to rapidly create such an extremely accurate and efficient antenna design without the need to manufacture prototypes has also enabled inexpensive research that promises to improve the system-level performance of microwave radiometers for upcoming space-flight missions. This paper will present details of the LRR antenna design and describe some other current edge-slot array accomplishments at Goddard Space Flight Center.

  6. 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

  7. 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.

  8. 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.

  9. Evolution of facility layout requirements and CAD (computer-aided design) system development

    SciTech Connect

    Jones, M. )

    1990-06-01

    The overall configuration of the Superconducting Super Collider (SSC) including the infrastructure and land boundary requirements were developed using a computer-aided design (CAD) system. The evolution of the facility layout requirements and the use of the CAD system are discussed. The emphasis has been on minimizing the amount of input required and maximizing the speed by which the output may be obtained. The computer system used to store the data is also described.

  10. A Rational Approach to the Optimal Design of Drugs.

    DTIC Science & Technology

    1986-07-16

    Recent advances in the rational design of drug molecules based on a graph-theoretical approach are briefly reviewed. Graph theory has not been widely recognized to date as an effective alternative to the empirical procedures currently prevailing in the development of new drugs . Moreover, the problems confronting researchers in this field are daunting in their great complexity. We advocate here a novel yet simple mathematical formalism which opens up a promising

  11. 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.

  12. Identification of Novel Drug Targets and Lead Compounds for Advanced Prostate Cancer through Genomic and Cheminformatic Analyses

    DTIC Science & Technology

    2015-08-01

    Proteomics, Cheminformatics, Computer- aided drug design, Small molecule inhibitors, biological assays, Compound validation. 16. SECURITY...aberrations Genomics Transcriptomics Proteomics Bioinformatics Cheminformatics Computer- aided drug design Small molecule inhibitors In silico compound...using the combined power of genomic analyses, protein structural modeling, computer- aided drug design and biological screening to develop new

  13. 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.

  14. A Bright Future for Evolutionary Methods in Drug Design.

    PubMed

    Le, Tu C; Winkler, David A

    2015-08-01

    Most medicinal chemists understand that chemical space is extremely large, essentially infinite. Although high-throughput experimental methods allow exploration of drug-like space more rapidly, they are still insufficient to fully exploit the opportunities that such large chemical space offers. Evolutionary methods can synergistically blend automated synthesis and characterization methods with computational design to identify promising regions of chemical space more efficiently. We describe how evolutionary methods are implemented, and provide examples of published drug development research in which these methods have generated molecules with increased efficacy. We anticipate that evolutionary methods will play an important role in future drug discovery.

  15. Effect of educational intervention on knowledge, perceived benefits, barriers and self-efficacy regarding AIDS preventive behaviors among drug addicts

    PubMed Central

    Bastami, Fatemeh; Mostafavi, Firoozeh; Hassanzadeh, Akbar

    2015-01-01

    Background and Objectives: Addicts account for approximately 68.15% of AIDS cases in Iran and injection drug users are considered as a major factor in the spread of AIDS in Iran. The purpose of this study was to determine the effect of an educational intervention on the perceived self-efficacy, benefits, and barriers concerning AIDS preventive behaviors among drug addicts in Khorramabad, Iran. Methods: This is a quasi-experimental study carried out in 2013 on 88 addicts kept in rehabilitations center in Khorramabad. The data collection instruments included a questionnaire on self-efficacy, perceived benefits, perceived barriers, knowledge and preventive behaviors regarding HIV. Data were analyzed by paired t-test, independent t-test, Chi-square and analysis of covariance. Results: Paired t-test showed that the mean scores for perceived benefits and barriers, knowledge and preventive behaviors significantly increased in the intervention group after the intervention than before the intervention. But the increase in self-efficacy score was not statistically significant. Conclusions: The results of this study showed that training and education based on the health belief model led to an increase in knowledge, self-efficacy, perceived benefits, performance and reduction in perceived barriers in addicts. It is recommended that future studies should include strategies for enhancing self-efficacy and perceived benefits as well as strategies for reducing barriers to the adoption of preventive behaviors. PMID:27462632

  16. Multi-objective optimization methods in drug design.

    PubMed

    Nicolaou, Christos A; Brown, Nathan

    2013-09-01

    Drug discovery is a challenging multi-objective problem where numerous pharmaceutically important objectives need to be adequately satisfied for a solution to be found. The problem is characterized by vast, complex solution spaces further perplexed by the presence of conflicting objectives. Multi-objective optimization methods, designed specifically to address such problems, have been introduced to the drug discovery field over a decade ago and have steadily gained in acceptance ever since. This paper reviews the latest multi-objective methods and applications reported in the literature, specifically in quantitative structure–activity modeling, docking, de novo design and library design. Further, the paper reports on related developments in drug discovery research and advances in the multi-objective optimization field.

  17. 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

  18. Sex and drugs and nuclear war: secular, developmental and type A influences upon adolescents' fears of the nuclear threat, AIDS and drug addiction.

    PubMed

    Wilkins, R; Lewis, C

    1993-03-01

    Researchers are divided over the significance of teenagers' expressed fear of nuclear war. This study of 3556 secondary school pupils examined whether (1) fear of nuclear war remains a feature of adolescent concern during the current east-west détente; (2) the examination of responses in a large sample reveals age and sex differences in such expressed fears; (3) worry about 'real world' issues like nuclear war, AIDS and drug addiction relates more generally to Type A proneness in adolescents. The results suggest that fewer teenagers spontaneously raise fear of nuclear war than in previous "pre-Glasnost" research in Britain, that such concern is expressed differentially according to the child's age and sex and that secondary school pupils who express concern about nuclear war and AIDS are more likely to show significantly higher Type A identification.

  19. 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.

  20. 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.

  1. 21 CFR 316.20 - Content and format of a request for orphan-drug designation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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...

  2. 21 CFR 316.20 - Content and format of a request for orphan-drug designation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  3. 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.

  4. 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.

  5. Design and fabrication of facial prostheses for cancer patient applying computer aided method and manufacturing (CADCAM)

    NASA Astrophysics Data System (ADS)

    Din, Tengku Noor Daimah Tengku; Jamayet, Nafij; Rajion, Zainul Ahmad; Luddin, Norhayati; Abdullah, Johari Yap; Abdullah, Abdul Manaf; Yahya, Suzana

    2016-12-01

    Facial defects are either congenital or caused by trauma or cancer where most of them affect the person appearance. The emotional pressure and low self-esteem are problems commonly related to patient with facial defect. To overcome this problem, silicone prosthesis was designed to cover the defect part. This study describes the techniques in designing and fabrication for facial prosthesis applying computer aided method and manufacturing (CADCAM). The steps of fabricating the facial prosthesis were based on a patient case. The patient was diagnosed for Gorlin Gotz syndrome and came to Hospital Universiti Sains Malaysia (HUSM) for prosthesis. The 3D image of the patient was reconstructed from CT data using MIMICS software. Based on the 3D image, the intercanthal and zygomatic measurements of the patient were compared with available data in the database to find the suitable nose shape. The normal nose shape for the patient was retrieved from the nasal digital library. Mirror imaging technique was used to mirror the facial part. The final design of facial prosthesis including eye, nose and cheek was superimposed to see the result virtually. After the final design was confirmed, the mould design was created. The mould of nasal prosthesis was printed using Objet 3D printer. Silicone casting was done using the 3D print mould. The final prosthesis produced from the computer aided method was acceptable to be used for facial rehabilitation to provide better quality of life.

  6. Prevalence and knowledge of sexual transmitted infections, drug abuse, and AIDS among male inmates in a Taiwan prison.

    PubMed

    Feng, Ming-Chu; Feng, Jui-Ying; Chen, Yen-Hsu; Chang, Pi-Yen; Lu, Po-Liang

    2012-12-01

    This cross-sectional, descriptive, correlational study performed a structured questionnaire survey of a Taiwan population of male prison inmates to determine the prevalence of sexually transmitted infections (STIs), intravenous drug users (IDUs), and drug abuse and to assess their knowledge of HIV/AIDS. The objective was to obtain data needed to control the spread of HIV. Out of 1000 questionnaires distributed, 908 valid questionnaires were returned. Inmates were classified into three groups: IDUs with HIV (13.5%), IDUs without HIV (49.3%), and non-IDUs without HIV (37.2%). A total of 115 (12.7%) inmates had contracted STIs other than HIV. Compared with inmates without HIV, those with HIV were more likely to have a junior high school education level or lower and a history of the following: employment as a blue-collar laborer, STI, unprotected sexual activity, and needle sharing during intravenous drug use. The longer they have used intravenous drugs, the higher the probability that they shared needles, and the more likely they contracted with HIV. Taiwanese male inmates had a low level of knowledge about safe sex and HIV transmission routes, except for sharing needles. The three groups did not significantly differ in HIV-related knowledge. Given the high percentage of IDU and HIV infection in male prison inmates in Taiwan, interventions are needed to educate this population in the increased risk of contracting HIV/AIDS associated with unsafe sex and needle sharing during illicit drug use. Such interventions are crucial for limiting the spread of HIV as this population reintegrates with the community.

  7. 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.

  8. Addressing metabolic activation as an integral component of drug design.

    PubMed

    Doss, George A; Baillie, Thomas A

    2006-01-01

    Formation of reactive intermediates by metabolism of xenobiotics represents a potential liability in drug discovery and development. Although it is difficult, if not impossible, to predict toxicities of drug candidates accurately, it is prudent to try to minimize bioactivation liabilities as early as possible in the stage of drug discovery and lead optimization. Measurement of covalent binding to liver microsomal proteins in the presence and the absence of NADPH, as well as the use of trapping agents such as glutathione or cyanide ions to provide structural information on reactive intermediates, have been used routinely to screen drug candidates. These in vitro experiments are often supplemented with in vivo covalent binding data in rats. The resulting data are not only used to eliminate potentially risky compounds, but, more importantly, they provide invaluable information to direct the Medicinal Chemistry group efforts to design analogs with less propensity to undergo bioactivation. Select case histories are presented in which this approach was successfully applied at Merck.

  9. 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. PMID:27721332

  10. 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.

  11. 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.

  12. 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.

  13. Paediatric Drug Development and Formulation Design-a European Perspective.

    PubMed

    Van Riet-Nales, Diana A; Kozarewicz, Piotr; Aylward, Brian; de Vries, Rutger; Egberts, Toine C G; Rademaker, Carin M A; Schobben, Alfred F A M

    2017-02-01

    The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize "better" medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the "Guideline on the Pharmaceutical Development of Medicines for Paediatric Use." Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline's key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions.

  14. Modification of planned postoperative occlusion in orthognathic surgery, based on computer-aided design/computer-aided manufacturing-engineered preoperative surgical simulation.

    PubMed

    Kang, Sang-Hoon; Kim, Moon-Key; You, Tae-Kwon; Lee, Ji-Yeon

    2015-01-01

    In orthognathic surgery, it is important to have a planned postoperative occlusion. A 3-dimensional preoperative simulation, based on 3-dimensional optically scanned occlusion data, can predict how the planned postoperative occlusion will affect the maxilla-mandibular relationship that results from orthognathic surgery. In this study we modified the planned postoperative occlusion, based on computer-aided design/computer-aided manufacturing-engineered preoperative surgical simulations. This modification made it possible to resolve the facial asymmetry of the patient successfully with a simple bilateral intraoral vertical ramus osteotomy and no additional maxillary or mandibular surgery.

  15. Mandibular reconstructions using computer-aided design/computer-aided manufacturing: A systematic review of a defect-based reconstructive algorithm.

    PubMed

    Tarsitano, Achille; Del Corso, Giacomo; Ciocca, Leonardo; Scotti, Roberto; Marchetti, Claudio

    2015-11-01

    Modern planning techniques, including computer-aided design/computer-aided manufacturing (CAD-CAM) can be used to plan reconstructive surgery, optimising aesthetic outcomes and functional rehabilitation. However, although many such applications are available, no systematic protocol yet describes the entire reconstructive procedure, which must include virtual planning, custom manufacture, and a reconstructive algorithm. We reviewed current practices in this novel field, analysed case series described in the literature, and developed a new, defect-based reconstructive algorithm. We also evaluated methods of mandibular reconstruction featuring virtual planning, the use of surgical guides, and laser printing of custom titanium bony plates to support composite free flaps, and evaluated their utility.

  16. 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.

  17. 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.

  18. Design of new polymeric formulations for drug nanocarriers

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

  19. 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)…

  20. 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.…

  1. 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.

  2. [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.

  3. Methods and software tools for computer-aided design of the spacecraft guidance, navigation and control systems

    NASA Astrophysics Data System (ADS)

    Somov, Yevgeny; Oparin, Gennady

    2017-01-01

    We shortly present results on development and employment of the software systems for computer-aided design of the spacecraft guidance. navigation and control systems - modeling, synthesis, nonlinear analysis, simulation and graphic mapping of dynamic processes.

  4. 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.

  5. On p53 revival using system oriented drug dosage design.

    PubMed

    Haseeb, Muhammad; Azam, Shumaila; Bhatti, A I; Azam, Rizwan; Ullah, Mukhtar; Fazal, Sahar

    2017-02-21

    We propose a new paradigm in the drug design for the revival of the p53 pathway in cancer cells. It is shown that the current strategy of using small molecule based Mdm2 inhibitors is not enough to adequately revive p53 in cancerous cells, especially when it comes to the extracting pulsating behavior of p53. This fact has come to notice when a novel method for the drug dosage design is introduced using system oriented concepts. As a test case, small molecule drug Mdm2 repressor Nutlin 3a is considered. The proposed method determines the dose of Nutlin to revive p53 pathway functionality. For this purpose, PBK dynamics of Nutlin have also been integrated with p53 pathway model. The p53 pathway is the focus of researchers for the last thirty years for its pivotal role as a frontline cancer suppressant protein due to its effect on cell cycle checkpoints and cell apoptosis in response to a DNA strand break. That is the reason for finding p53 being absent in more than 50% of tumor cancers. Various drugs have been proposed to revive p53 in cancer cells. Small molecule based drugs are at the foremost and are the subject of advanced clinical trials. The dosage design of these drugs is an important issue. We use control systems concepts to develop the drug dosage so that the cancer cells can be treated in appropriate time. We investigate by using a computational model how p53 protein responds to drug Nutlin 3a, an agent that interferes with the MDM2-mediated p53 regulation. The proposed integrated model describes in some detail the regulation network of p53 including the negative feedback loop mediated by MDM2 and the positive feedback loop mediated by Mdm2 mRNA as well as the reversible represses of MDM2 caused by Nutlin. The reported PBK dynamics of Nutlin 3a are also incorporated to see the full effect. It has been reported that p53 response to stresses in two ways. Either it has a sustained (constant) p53 response, or there are oscillations in p53 concentration. The

  6. The evolution of drug design at Merck Research Laboratories

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  7. 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…

  8. 21 CFR 344.50 - Labeling of earwax removal aid drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... following: “For occasional use as an aid to” (which may be followed by: “soften, loosen, and”) “remove... treatment may be removed by gently flushing the ear with warm water, using a soft rubber bulb ear...

  9. 21 CFR 344.50 - Labeling of earwax removal aid drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... following: “For occasional use as an aid to” (which may be followed by: “soften, loosen, and”) “remove... treatment may be removed by gently flushing the ear with warm water, using a soft rubber bulb ear...

  10. 21 CFR 344.50 - Labeling of earwax removal aid drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... following: “For occasional use as an aid to” (which may be followed by: “soften, loosen, and”) “remove... treatment may be removed by gently flushing the ear with warm water, using a soft rubber bulb ear...

  11. 21 CFR 344.50 - Labeling of earwax removal aid drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... following: “For occasional use as an aid to” (which may be followed by: “soften, loosen, and”) “remove... treatment may be removed by gently flushing the ear with warm water, using a soft rubber bulb ear...

  12. 21 CFR 344.50 - Labeling of earwax removal aid drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... following: “For occasional use as an aid to” (which may be followed by: “soften, loosen, and”) “remove... treatment may be removed by gently flushing the ear with warm water, using a soft rubber bulb ear...

  13. 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

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

    NASA Astrophysics Data System (ADS)

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

    2012-08-01

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

  15. Antiretroviral manufacturers and the challenge of universal access to drugs through the Brazilian National STD/AIDS Program.

    PubMed

    do Lago, Regina Ferro; Costa, Nilson do Rosário

    2009-10-01

    This article describes the antiretroviral (ARV) manufacturing market in Brazil and contextualizes the challenges for the public policy of supplying ARVs through the National STD/AIDS Program. Increasing expenditure on these drugs is the main source of uncertainty for the policy's future. Brazil's domestic scenario is one of growing external dependence, both for the finished drugs and the active ingredients. Experience in the National Program has shown that it is the state's role to provide public goods, which presupposes ensuring mutual compatibility between company interests and social interests. This balance is currently at stake in Brazil, since structural changes in the market have raised challenges for the National Program's sustainability, requiring new public policy instruments in defense of the collective interest. The article drew on a literature review, using bibliographic indexing sources, systematic organization of primary data, government publications, relevant legislation, research reports, and articles recommended by experts from the field.

  16. Structure-based methods for predicting target mutation-induced drug resistance and rational drug design to overcome the problem.

    PubMed

    Hao, Ge-Fei; Yang, Guang-Fu; Zhan, Chang-Guo

    2012-10-01

    Drug resistance has become one of the biggest challenges in drug discovery and/or development and has attracted great research interests worldwide. During the past decade, computational strategies have been developed to predict target mutation-induced drug resistance. Meanwhile, various molecular design strategies, including targeting protein backbone, targeting highly conserved residues and dual/multiple targeting, have been used to design novel inhibitors for combating the drug resistance. In this article we review recent advances in development of computational methods for target mutation-induced drug resistance prediction and strategies for rational design of novel inhibitors that could be effective against the possible drug-resistant mutants of the target.

  17. Design of a cervical collar device to facilitate and accelerate implementation of first aid.

    PubMed

    Işık, Hakan; Saraçoğlu, Esra; Harmanci, Hüseyin; Güler, Inan

    2010-08-01

    Frequently there are disasters all over the world-fires, earthquakes, or even some unexpected shocking catastrophes. Hence people injured, or even died. Lifesaving actions begin with the initiation of the chain of survival. With every minute that passes without medical action being taken, the probability of being able to save the patients life decreases by ten percent. After 10 min there is normally no chance of resuscitation being successful. First aid is emergency treatment given before regular medical aid can be obtained. And it is a concept of first hands-on measures performed in a medical emergency by laypersons. The major aim of this study is to develop an easy-feasible cervical collar, for facilitating and accelerating implementation of first aid especially in case of collective injuries. The developed device is different from the cervical collars which are used to treat the neck pain. In the present study, the heartbeat is obtained by detecting pulse with the stethoscope that is a part of the developed device and fixed on the carorid artery. The obtained heartbeat signal has been processed by the electronic control circuit and the used LED has given light according to the patient's life signal. Although there are some disadvantages of the developed system, the precautions for these cases have been taken and the system has been tried to design in order to operate sensibly.

  18. Optimal serial dilutions designs for drug discovery experiments.

    PubMed

    Donev, Alexander N; Tobias, Randall D

    2011-05-01

    Dose-response studies are an essential part of the drug discovery process. They are typically carried out on a large number of chemical compounds using serial dilution experimental designs. This paper proposes a method of selecting the key parameters of these designs (maximum dose, dilution factor, number of concentrations and number of replicated observations for each concentration) depending on the stage of the drug discovery process where the study takes place. This is achieved by employing and extending results from optimal design theory. Population D- and D(S)-optimality are defined and used to evaluate the precision of estimating the potency of the tested compounds. The proposed methodology is easy to use and creates opportunities to reduce the cost of the experiments without compromising the quality of the data obtained in them.

  19. Current Challenges to the United States' AIDS Drug Assistance Program and Possible Implications of the Affordable Care Act

    PubMed Central

    McManus, Kathleen A.; Engelhard, Carolyn L.; Dillingham, Rebecca

    2013-01-01

    AIDS Drug Assistance Programs, enacted through the Ryan White Comprehensive AIDS Resources Emergency Act of 1990, are the “payer of last resort” for prescription medications for lower income, uninsured, or underinsured people living with HIV/AIDS. ADAPs face declining funding from the federal government. State funding of ADAP is discretionary, but some states increased their contributions to meet the gap in funding. The demand for ADAP support is increasing as people living with HIV are living longer; the antiretroviral therapy (ART) guidelines have been changed to recommend initiation of treatment for all; the United States is increasing HIV testing goals; and the recession continues. In the setting of increased demand and limited funding, ADAPs are employing cost containment measures. Since 2010, emergency federal funds have bailed out ADAP, but these are not sustainable. In the coming years, providers and policy makers associated with HIV care will need to navigate the implementation of the Affordable Care Act (ACA). Lessons learned from the challenges associated with providing sustainable access to ART for vulnerable populations through ADAP should inform upcoming decisions about how to ensure delivery of ART during and after the implementation of the ACA. PMID:23573418

  20. GA-Based Computer-Aided Electromagnetic Design of Two-Phase SRM for Compressor Drives

    NASA Astrophysics Data System (ADS)

    Kano, Yoshiaki; Kosaka, Takashi; Matsui, Nobuyuki

    This paper presents an approach to Genetic Algorithm (GA)-based computer-aided autonomous electromagnetic design of 2-phase Switched Reluctance Motor drives. The proposed drive is designed for compressor drives in low-priced refrigerators as an alternative to existing brushless DC motors drives with rare-earth magnets. In the proposed design approach, three GA loops work to optimize the lamination design so as to meet the requirements for the target application under the given constraints while simultaneously fine-tuning the control parameters. To achieve the design optimization within an acceptable CPU-time, the repeated-calculation required to obtain fitness evaluation in the proposed approach does not use FEM, but consists of geometric flux tube-based non-linear magnetic analysis and a dynamic simulator based on an analytical expression of the magnetizing curves obtained from the non-linear magnetic analysis. The design results show the proposed approach can autonomously find a feasible design solution of SRM drive for the target application from huge search space. The experimental studies using a 2-phase 8/6 prototype manufactured in accordance with the optimized design parameters show the validity of the proposed approach.

  1. Pharmacophore based drug design approach as a practical process in drug discovery.

    PubMed

    Gao, Qingzhi; Yang, Lulu; Zhu, Yongqiang

    2010-03-01

    This review summarizes the background and updated progress of pharmacophore based drug design and provides the fundamental approach strategies on both structure based and ligand based pharmacophore approaches. The different programs and methodologies enable the implementation of more accurate and sophisticated pharmacophore model generation and application in drug discovery. This review will discuss and illustrate their advantages in pharmacophore based virtual screening and exemplify the detailed application workflow, which can be easily utilized by pharmaceutical bench work medicinal chemists. Pharmacophore based drug design process includes pharmacophore modeling and validation; pharmacophore based virtual screening, virtual hits profiling and lead identification. Strategies and proven methodologies for pharmacophore modeling are described including common feature and 3D QSAR based pharmacophore generation as well as structure based pharmacophore development. Different virtual screening strategies will be described in this review with detailed case studies for supporting practical applications. Representative success examples of pharmacophore based virtual screening for lead generation will be collected to demonstrate capabilities.

  2. 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.

  3. A Novel Computer-Aided Approach for Parametric Investigation of Custom Design of Fracture Fixation Plates

    PubMed Central

    2017-01-01

    The present study proposes an integrated computer-aided approach combining femur surface modeling, fracture evidence recover plate creation, and plate modification in order to conduct a parametric investigation of the design of custom plate for a specific patient. The study allows for improving the design efficiency of specific plates on the patients' femur parameters and the fracture information. Furthermore, the present approach will lead to exploration of plate modification and optimization. The three-dimensional (3D) surface model of a detailed femur and the corresponding fixation plate were represented with high-level feature parameters, and the shape of the specific plate was recursively modified in order to obtain the optimal plate for a specific patient. The proposed approach was tested and verified on a case study, and it could be helpful for orthopedic surgeons to design and modify the plate in order to fit the specific femur anatomy and the fracture information. PMID:28203270

  4. 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.

  5. 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.

  6. A Novel Computer-Aided Approach for Parametric Investigation of Custom Design of Fracture Fixation Plates.

    PubMed

    Chen, Xiaozhong; He, Kunjin; Chen, Zhengming

    2017-01-01

    The present study proposes an integrated computer-aided approach combining femur surface modeling, fracture evidence recover plate creation, and plate modification in order to conduct a parametric investigation of the design of custom plate for a specific patient. The study allows for improving the design efficiency of specific plates on the patients' femur parameters and the fracture information. Furthermore, the present approach will lead to exploration of plate modification and optimization. The three-dimensional (3D) surface model of a detailed femur and the corresponding fixation plate were represented with high-level feature parameters, and the shape of the specific plate was recursively modified in order to obtain the optimal plate for a specific patient. The proposed approach was tested and verified on a case study, and it could be helpful for orthopedic surgeons to design and modify the plate in order to fit the specific femur anatomy and the fracture information.

  7. 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.

  8. Risk Behaviors and Perceptions of AIDS among Street Injection Drug Users.

    ERIC Educational Resources Information Center

    Rhodes, Fen; And Others

    1990-01-01

    Conducted 325 survey interviews and 22 guided in-depth interviews with injection drug users to document drug usage and injection patterns, sexual practices, perceived risk of Human Immunodeficiency Virus infection, sources of health information, and knowledge and attitudes about Acquired Immune Deficiency Syndrome. (Author/ABL)

  9. Design of a controlled-brake orthosis for FES-aided gait.

    PubMed

    Goldfarb, M; Durfee, W K

    1996-03-01

    Functional electrical stimulation (FES) is a means of restoring gait to individuals with spinal cord injury, but the performance of most FES-aided gait systems is hampered by the rapid muscle fatigue which results from stimulated muscle contraction and the inadequate control of joint torques necessary to produce desired limb trajectories. The controlled-brake orthosis (CBO) addresses these limitations by utilizing FES in combination with a long-leg brace that contains controllable friction brakes at the knees and hips. A laboratory version of the CBO utilizing computer-controlled magnetic particle brakes at the joints was designed and constructed, and preliminary results with a single spinal cord injury (SCI) subject have demonstrated reduced fatigue and more repeatable gait trajectories when compared to FES-aided gait without the brace. Significant work remains to demonstrate the efficacy of the concept across a wide range of SCI subjects and to design a system which meets appropriate user requirements of size, weight, cosmesis, ease of use and cost. The primary purpose of the paper is to detail the design of the CBO.

  10. 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.

  11. User-Friendly, Syntax Directed Input to a Computer Aided Design System.

    DTIC Science & Technology

    1983-06-01

    indepen- dern-. oblems arise in both compu:er aided design and in software development as a result of multipla types cf computz , mUtiple languages...Base CONLAN. Ease CONLAN is defined cy three i- ms , a set of object types and cperations, syntax, and a comPuta-IoL model. It is defined with Primitive...ycsjum on Computer Hardware= DescrT:--c-: -Lanquaqes. ~ p. =-3’EEET73 28. H1Il, F. J., and Petezzcn, J. R., DjZt4- S Lt-= Ms : Hardware O~gan iza,,i.n cand

  12. 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...

  13. 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...

  14. AIDS Drug Assistance Programs: managers confront uncertainty and need to adapt as the Affordable Care Act kicks in.

    PubMed

    Martin, Erika G; Meehan, Terence; Schackman, Bruce R

    2013-06-01

    With the Affordable Care Act set to expand insurance coverage to millions more Americans next year, existing discretionary health programs that receive federal support might find themselves competing for funds as the health reform law is fully implemented. To assess the implications the Affordable Care Act might have for discretionary health programs, we focused on state AIDS Drug Assistance Programs, which provide free medications to low-income HIV patients. We conducted semistructured interviews with program managers from twenty-two states. Many of the managers predicted that their programs will change focus to provide "wrap-around services," such as helping newly insured clients finance out-of-pocket expenses, including copayments, deductibles, and premiums. Although program managers acknowledged that they must adapt to a changing environment, many said that they were overwhelmed by the complexity of the Affordable Care Act, and some expressed fear that state AIDS Drug Assistance Programs would be eliminated entirely. To remain viable, such programs must identify and justify the need for services in the context of the Affordable Care Act and receive sufficient political support and funding.

  15. User's manual: Computer-aided design programs for inductor-energy-storage dc-to-dc electronic power converters

    NASA Technical Reports Server (NTRS)

    Huffman, S.

    1977-01-01

    Detailed instructions on the use of two computer-aided-design programs for designing the energy storage inductor for single winding and two winding dc to dc converters are provided. Step by step procedures are given to illustrate the formatting of user input data. The procedures are illustrated by eight sample design problems which include the user input and the computer program output.

  16. 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

  17. An Automated Tool for Developing Experimental Designs: The Computer-Aided Design Reference for Experiments (CADRE)

    DTIC Science & Technology

    2009-01-01

    survey procedures, and cognitive task analysis), system design methods (e.g., focus groups , design guidelines, specifications, and requirements), and...LABORATORY - HRED ATTN AMSRD ARL HR MZ A DAVISON 199 E 4TH ST STE C TECH PARK BLG 2 FT LEONARD WOOD MO 65473-1949 1 ARMY RSCH LABORATORY

  18. Accelerating Design of Batteries Using Computer-Aided Engineering Tools (Presentation)

    SciTech Connect

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

    2010-11-01

    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.

  19. 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

  20. 21 CFR 516.30 - Annual reports for a MUMS-designated drug.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Drug Development that includes the following information: (a) A short account of the progress of drug... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Annual reports for a MUMS-designated drug. 516.30 Section 516.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  1. 21 CFR 516.30 - Annual reports for a MUMS-designated drug.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Drug Development that includes the following information: (a) A short account of the progress of drug... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Annual reports for a MUMS-designated drug. 516.30 Section 516.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  2. 21 CFR 516.30 - Annual reports for a MUMS-designated drug.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drug Development that includes the following information: (a) A short account of the progress of drug... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Annual reports for a MUMS-designated drug. 516.30 Section 516.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  3. Problems of drug abuse, HIV and AIDS: the burden of care in one general practice.

    PubMed Central

    Ronald, P J; Witcomb, J C; Robertson, J R; Roberts, J J; Shishodia, P C; Whittaker, A

    1992-01-01

    Responsibility for many of the problems of intravenous drug abuse and human immunodeficiency virus (HIV) infection lies with community care agencies, such as general practitioners, community psychiatric and district nurses and drug agencies. It is in general practice that this burden is most clearly observed, given that general practitioners are in charge of the day-to-day care of patients. In an attempt to quantify this workload in an inner city practice with 11,200 patients, data were gathered from several sources relating to drug use and HIV infection. The study identified 432 patients who had consulted with problems of drug abuse and/or HIV infection over the period 1981-90. Among this group of patients 161 (37%) were HIV antibody positive. Among 191 drug abusers who were still registered with the practice in 1990 dihydrocodeine was the most commonly prescribed substitute treatment (130 patients) and only nine patients were prescribed methadone. Forty seven per cent of drug users continued to inject drugs occasionally. However, analysis of urine samples revealed that there was a shift away from injecting mainly heroin to multiple drug use, including benzodiazepines, usually originating from prescribed sources. Drug abusers who were HIV positive consulted their general practitioner significantly more often over one year than those who were not (mean 24.9 versus 15.8 consultations, P < 0.01). However, there was no significant difference between these two groups in terms of days spent in hospital. A total of 61 patients were referred to a community psychiatric nurse over an eight month period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1419244

  4. Behavioral outcomes of AIDS educational interventions for drug users in short-term treatment.

    PubMed Central

    McCusker, J; Stoddard, A M; Zapka, J G; Lewis, B F

    1993-01-01

    This paper reports the behavioral outcomes of informational vs enhanced small-group educational interventions for drug users among 407 subjects in a short-term drug treatment program. Logistic regression was used to analyze drug use and sexual behaviors at the final follow-up visit. Among lower risk subjects, the enhanced intervention was more effective in reducing injection practices that produced risks in terms of human immunodeficiency virus infection; among those at highest risk, the informational interventions were more effective. The enhanced intervention was more effective than the informational interventions in reducing cocaine use at follow-up. No differential intervention effect on sexual risk behaviors was found. PMID:8214241

  5. 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

  6. Computational methods for drug design and discovery: focus on China.

    PubMed

    Zheng, Mingyue; Liu, Xian; Xu, Yuan; Li, Honglin; Luo, Cheng; Jiang, Hualiang

    2013-10-01

    In the past decades, China's computational drug design and discovery research has experienced fast development through various novel methodologies. Application of these methods spans a wide range, from drug target identification to hit discovery and lead optimization. In this review, we firstly provide an overview of China's status in this field and briefly analyze the possible reasons for this rapid advancement. The methodology development is then outlined. For each selected method, a short background precedes an assessment of the method with respect to the needs of drug discovery, and, in particular, work from China is highlighted. Furthermore, several successful applications of these methods are illustrated. Finally, we conclude with a discussion of current major challenges and future directions of the field.

  7. 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...

  8. Experimental design for optimizing drug release from silicone elastomer matrix and investigation of transdermal drug delivery.

    PubMed

    Snorradóttir, Bergthóra S; Gudnason, Pálmar I; Thorsteinsson, Freygardur; Másson, Már

    2011-04-18

    Silicone elastomers are commonly used for medical devices and external prosthesis. Recently, there has been growing interest in silicone-based medical devices with enhanced function that release drugs from the elastomer matrix. In the current study, an experimental design approach was used to optimize the release properties of the model drug diclofenac from medical silicone elastomer matrix, including a combination of four permeation enhancers as additives and allowing for constraints in the properties of the material. The D-optimal design included six factors and five responses describing material properties and release of the drug. The first experimental object was screening, to investigate the main and interaction effects, based on 29 experiments. All excipients had a significant effect and were therefore included in the optimization, which also allowed the possible contribution of quadratic terms to the model and was based on 38 experiments. Screening and optimization of release and material properties resulted in the production of two optimized silicone membranes, which were tested for transdermal delivery. The results confirmed the validity of the model for the optimized membranes that were used for further testing for transdermal drug delivery through heat-separated human skin. The optimization resulted in an excipient/drug/silicone composition that resulted in a cured elastomer with good tensile strength and a 4- to 7-fold transdermal delivery increase relative to elastomer that did not contain excipients.

  9. Attitude of Health Care Workers (HCWs) toward Patients Affected by HIV/AIDS and Drug Users: A Cross-Sectional Study

    PubMed Central

    Ledda, Caterina; Cicciù, Francesca; Puglisi, Beatrice; Ramaci, Tiziana; Nunnari, Giuseppe; Rapisarda, Venerando

    2017-01-01

    Caring for HIV/AIDS patients and/or drug users requires health care workers (HCWs) to have good knowledge of the issues. Cultural differences in HCWs, combined with professional ethics and personal beliefs, could also result in conflicting attitudes, leading to difficulties related to looking after people affected by HIV/AIDS or drug users. A cross-sectional study was carried out to assess the attitude towards HIV/AIDS patients and/or drug users in a sample of workers operating in a large university hospital in southern Italy. A total of 736 workers were surveyed from May to November 2016. During the periodic occupational health surveillance, a questionnaire was administered about attitudes of discrimination, acceptance and fear towards these patients. Respondents showed average levels of acceptance to HIV/AIDS and drug user patients. As years of experience and professional training increased, scores for discrimination, acceptance of HIV/AIDS, acceptance of drug users and fear decreased. Factors positively influencing levels of attitudes were being female and younger. Supplementary education is needed to strengthen the awareness of HCWs. PMID:28282937

  10. Attitude of Health Care Workers (HCWs) toward Patients Affected by HIV/AIDS and Drug Users: A Cross-Sectional Study.

    PubMed

    Ledda, Caterina; Cicciù, Francesca; Puglisi, Beatrice; Ramaci, Tiziana; Nunnari, Giuseppe; Rapisarda, Venerando

    2017-03-09

    Caring for HIV/AIDS patients and/or drug users requires health care workers (HCWs) to have good knowledge of the issues. Cultural differences in HCWs, combined with professional ethics and personal beliefs, could also result in conflicting attitudes, leading to difficulties related to looking after people affected by HIV/AIDS or drug users. A cross-sectional study was carried out to assess the attitude towards HIV/AIDS patients and/or drug users in a sample of workers operating in a large university hospital in southern Italy. A total of 736 workers were surveyed from May to November 2016. During the periodic occupational health surveillance, a questionnaire was administered about attitudes of discrimination, acceptance and fear towards these patients. Respondents showed average levels of acceptance to HIV/AIDS and drug user patients. As years of experience and professional training increased, scores for discrimination, acceptance of HIV/AIDS, acceptance of drug users and fear decreased. Factors positively influencing levels of attitudes were being female and younger. Supplementary education is needed to strengthen the awareness of HCWs.

  11. 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-6Al-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 utilize the upper-bound and the slab methods of analysis, and are capable of predicting the lateral spread, roll-separating force, roll torque and local stresses, strains and strain rates. This computer-aided design (CAD) system is also capable of simulating the actual rolling process and thereby designing roll-pass schedule in rolling of an airfoil or similar shape. The predictions from the CAD system were verified with respect to cold rolling of mild steel plates. The system is being applied to cold and hot isothermal rolling of an airfoil shape, and will be verified with respect to laboratory experiments under controlled conditions.

  12. Computer-aided design and manufacturing in craniomaxillofacial surgery: the new state of the art.

    PubMed

    Levine, Jamie P; Patel, Ashish; Saadeh, Pierre B; Hirsch, David L

    2012-01-01

    The goal of this article was to illustrate the ease in which virtual surgery and computer-aided design and manufacturing can be used by the craniomaxillofacial surgeon to create tremendously accurate postoperative results and provide confidence with even the most complex three-dimensional bony reconstructions. With advancements in software technology and three-dimensional printing, our ability to plan and execute precise bony reconstruction has become a reality. With this technology, guides can be made to ensure exact bony repositioning or replacement. These guides can help guide cutting of the bone and can act as splints to precisely reposition the bone and direct plate placement. With use of these computer-aided design and manufacturing guides and the addition of guidance technology, the position of the bone can be guaranteed intraoperatively. We review our unique and advanced method in approaching some of these problems and illustrate the application of these techniques in mandibular reconstruction, orthognathic surgery, maxillofacial trauma, and temporomandibular joint reconstruction. This technology continues to evolve, and our indications for its application continue to grow. This article represents only a small portion of the types of cases in which these techniques have already been applied.

  13. Design and implementation of a bluetooth-based band-aid pulse rate sensor

    NASA Astrophysics Data System (ADS)

    Kumar, Prashanth S.; Oh, Sechang; Rai, Pratyush; Kwon, Hyeokjun; Banerjee, Nilanjan; Varadan, Vijay K.

    2011-04-01

    Remote patient monitoring systems capable of collecting vital patient data such as blood pressure readings, Electrocardiograph (ECG) waveforms, and heart rate can obviate the need for repeated visits to the hospital. Moreover, such systems that continuously monitor the human physiology can provide valuable data to prognosticate the onset of critical health problems. The key to such remote health diagnostics is the design of minimally intrusive, low cost sensors that do not impede a patient's quotidian life but at the same time collect reliable noise free data. To this end, in this paper, we design and implement a Bluetooth-based wireless sensor system with a disposable sensor element and a reusable wireless component that can be worn as a "band-aid". The sensor is a piezoelectric polymer film placed on the wrist in proximity to the radial artery. The band-aid sized sensor allows non-intrusive monitoring of the pulsatile flow of blood in the artery. The sensor, using the Bluetooth module, can communicate with any Bluetooth enabled computer, mobile phone, or PDA. The data collected from the patient can be remotely viewed and analyzed by a physician.

  14. Revisiting de novo drug design: receptor based pharmacophore screening.

    PubMed

    Amaravadhi, Harikishore; Baek, Kwanghee; Yoon, Ho Sup

    2014-01-01

    De novo drug design methods such as receptor or protein based pharmacophore modeling present a unique opportunity to generate novel ligands by employing the potential binding sites even when no explicit ligand information is known for a particular target. Recent developments in molecular modeling programs have enhanced the ability of early programs such as LUDI or Pocket that not only identify the key interactions or hot spots at the suspected binding site, but also and convert these hot spots into three-dimensional search queries and virtual screening of the property filtered synthetic libraries. Together with molecular docking studies and consensus scoring schemes they would enrich the lead identification processes. In this review, we discuss the ligand and receptor based de novo drug design approaches with selected examples.

  15. Intelligent system design for bionanorobots in drug delivery.

    PubMed

    Fletcher, Mark; Biglarbegian, Mohammad; Neethirajan, Suresh

    A nanorobot is defined as any smart structure which is capable of actuation, sensing, manipulation, intelligence, and swarm behavior at the nanoscale. In this study, we designed an intelligent system using fuzzy logic for diagnosis and treatment of tumors inside the human body using bionanorobots. We utilize fuzzy logic and a combination of thermal, magnetic, optical, and chemical nanosensors to interpret the uncertainty associated with the sensory information. Two different fuzzy logic structures, for diagnosis (Mamdani structure) and for cure (Takagi-Sugeno structure), were developed to efficiently identify the tumors and treat them through delivery of effective dosages of a drug. Validation of the designed system with simulated conditions proved that the drug delivery of bionanorobots was robust to reasonable noise that may occur in the bionanorobot sensors during navigation, diagnosis, and curing of the cancer cells. Bionanorobots represent a great hope for successful cancer therapy in the near future.

  16. LIFESPAN: A tool for the computer-aided design of longitudinal studies

    PubMed Central

    Brandmaier, Andreas M.; von Oertzen, Timo; Ghisletta, Paolo; Hertzog, Christopher; Lindenberger, Ulman

    2015-01-01

    Researchers planning a longitudinal study typically search, more or less informally, a multivariate space of possible study designs that include dimensions such as the hypothesized true variance in change, indicator reliability, the number and spacing of measurement occasions, total study time, and sample size. The main search goal is to select a research design that best addresses the guiding questions and hypotheses of the planned study while heeding applicable external conditions and constraints, including time, money, feasibility, and ethical considerations. Because longitudinal study selection ultimately requires optimization under constraints, it is amenable to the general operating principles of optimization in computer-aided design. Based on power equivalence theory (MacCallum et al., 2010; von Oertzen, 2010), we propose a computational framework to promote more systematic searches within the study design space. Starting with an initial design, the proposed framework generates a set of alternative models with equal statistical power to detect hypothesized effects, and delineates trade-off relations among relevant parameters, such as total study time and the number of measurement occasions. We present LIFESPAN (Longitudinal Interactive Front End Study Planner), which implements this framework. LIFESPAN boosts the efficiency, breadth, and precision of the search for optimal longitudinal designs. Its initial version, which is freely available at http://www.brandmaier.de/lifespan, is geared toward the power to detect variance in change as specified in a linear latent growth curve model. PMID:25852596

  17. Computer-aided design comparisons of monolithic and hybrid MEM-tunable VCSELs

    NASA Astrophysics Data System (ADS)

    Ochoa, Edward M.; Nelson, Thomas R., Jr.; Blum-Spahn, Olga; Lott, James A.

    2003-07-01

    We report and use our micro-electro-mechanically tunable vertical cavity surface emitting laser (MEM-TVCSEL) computer-aided design methodology to investigate the resonant frequency design space for monolithic and hybrid MEM-TVCSELs. For various initial optical air gap thickness, we examine the sensitivity of monolithic or hybrid MEM-TVCSEL resonant frequency by simulating zero, two, and four percent variations in III-V material growth thickness. As expected, as initial optical airgap increases, tuning range decreases due to less coupling between the active region and the tuning mirror. However, each design has different resonant frequency sensitivity to variations in III-V growth parameters. In particular, since the monolithic design is comprised of III-V material, the shift in all growth thicknesses significantly shifts the resonant frequency response. However, for hybrid MEMTVCSELs, less shift results, since the lower reflector is an Au mirror with reflectivity independent of III-V growth variations. Finally, since the hybrid design is comprised of a MUMPS polysilicon mechanical actuator, pull-in voltage remains independent of the initial optical airgap between the tuning reflector and the III-V material. Conversely, as the initial airgap increases in the monolithic design, the pull-in voltage significantly increases.

  18. Establishment of a Computer-Aided Design (CAD)/Computer-Aided Manufacturing (CAM) Process for the Production of Cold Forged Gears

    DTIC Science & Technology

    1984-01-01

    Continue on reverse side if necessary and Identify by block number) Computer Aided Design/Manufacturing (CAD/CAM), Spur and Helical Gears, Cold Forging...for cold forging spur and helical gears. The geometry of the spur and helical gears has been obtained from the kinematics of the hobbing/shaper machines...or shaping) to cut the electrode for a helical gear die were then computed using the corrections described above. A computer program called GEARDI

  19. Computer aided design and manufacturing of composite propfan blades for a cruise missile wind tunnel model

    NASA Technical Reports Server (NTRS)

    Thorp, Scott A.; Downey, Kevin M.

    1992-01-01

    One of the propulsion concepts being investigated for future cruise missiles is advanced unducted propfans. To support the evaluation of this technology applied to the cruise missile, a joint DOD and NASA test project was conducted to design and then test the characteristics of the propfans on a 0.55-scale, cruise missile model in a NASA wind tunnel. The configuration selected for study is a counterrotating rearward swept propfan. The forward blade row, having six blades, rotates in a counterclockwise direction, and the aft blade row, having six blades, rotates in a clockwise direction, as viewed from aft of the test model. Figures show the overall cruise missile and propfan blade configurations. The objective of this test was to evaluate propfan performance and suitability as a viable propulsion option for next generation of cruise missiles. This paper details the concurrent computer aided design, engineering, and manufacturing of the carbon fiber/epoxy propfan blades as the NASA Lewis Research Center.

  20. Computer-aided design and distributed system technology development for large space structures

    NASA Technical Reports Server (NTRS)

    Armstrong, Ernest S.; Joshi, Suresh M.

    1986-01-01

    Proposed large space structures have many characteristics that make them difficult to analyze and control. They are highly flexible, with components mathematically modeled by partial differential equations or very large systems of ordinary differential equations. They have many resonant frequencies, typically low and closely spaced. Natural damping may be low and/or improperly modeled. Coupled with stringent operational requirements of orientation, shape control, and vibration suppression, and the inability to perform adequate ground testing, these characteristics present an unconventional identification and control design problem to the systems theorist. Some of the research underway within Langley's Spacecraft Control Branch, Guidance and Control Division aimed at developing theory and algorithms to treat large space structures systems identification and control problems is described. The research areas to be considered are computer-aided design algorithms, and systems identification and control of distributed systems.