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Sample records for aided drug design

  1. Computer-aided drug designing.

    PubMed

    Gore, Mohini; Desai, Neetin S

    2014-01-01

    Computer-aided drug designing has emerged as a cost-effective and rapid tool for the discovery of newer therapeutic agents. Several algorithms have been developed to analyze protein structure and function, to identify interacting ligands, active site residues, and to study protein-ligand interactions, which can eventually lead to the identification of new drugs. In silico drug designing involves identification of the target protein which is responsible for the development of the disease under study. The three-dimensional structure of the protein can be predicted using homology modeling, while molecular docking is applied to study the interaction of a drug molecule with the protein. The best orientation of the ligand-protein docked structure which has overall minimum energy needs to be obtained. In silico methods can be used to identify potential drugs for various diseases. Thus, computer-aided drug designing has become an indispensible and integral part of the drug discovery process. PMID:24870144

  2. Current topics in computer-aided drug design.

    PubMed

    Taft, Carlton A; Da Silva, Vinicius Barreto; Da Silva, Carlos Henrique Tomich De Paula

    2008-03-01

    The addition of computer-aided drug design (CADD) technologies to the research and drug discovery approaches could lead to a reduction of up to 50% in the cost of drug design. Designing a drug is the process of finding or creating a molecule which has a specific activity on a biological organism. Development and drug discovery is a time-consuming, expensive, and interdisciplinary process whereas scientific advancements during the past two decades have altered the way pharmaceutical research produces new bioactive molecules. Advances in computational techniques and hardware solutions have enabled in silico methods to speed up lead optimization and identification. We will review current topics in computer-aided molecular design underscoring some of the most recent approaches and interdisciplinary processes. We will discuss some of the most efficient pathways and design. PMID:18214973

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

    PubMed

    Zhang, Qiansen; Gao, Zhaobing; Yang, Huaiyu

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1995-04-01

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

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

    PubMed

    Zeng, Huahui; Wu, Xiangxiang

    2016-10-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the excessive deposition of amyloids in the brain. The pathological features mainly include the extracellular amyloid plaques and intracellular neurofibrillary tangles, which are the production of amyloid precursor protein (APP) processed by the α-, β- and γ-secretases. Based on the amyloid cascade hypotheses of AD, a large number of amyloid-β agents and secretase inhibitors against AD have been recently developed by using computational methods. This review article describes pathophysiology of AD and the structure of the Aβ plaques, β- and γ-secretases, and discusses the recent advances in the development of the amyloid agents for AD therapy and diagnosis by using Computer-Aided Drug Design approach. PMID:26415837

  6. Progress of computer-aided drug design (CADD) of proteasome inhibitors.

    PubMed

    Lei, Meng; Liu, Yunde; Zhu, Yongqiang; Liu, Zhenming

    2011-12-01

    The target proteasome has been the focus of drug discovery since the first drug bortezomib was launched in 2003. Many structurally diverse proteasome inhibitors were discovered and even some of them entered the clinical trials. Due to rapid technological progress in chemistry, bioinformatics, structural biology and computer technology, computer-aided drug design (CADD) plays a more and more important role in today's drug discovery. Many CADD technologies were employed in designing various inhibitors of proteasome in the past years. This review gives a global description of the development of computer-aided proteasome inhibitor design by using different commercial or academic software. The binding modes of some structurally novel inhibitors with proteasome were visualized with these new technologies. PMID:21824106

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. 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

  10. A novel integrated framework and improved methodology of computer-aided drug design.

    PubMed

    Chen, Calvin Yu-Chian

    2013-01-01

    Computer-aided drug design (CADD) is a critical initiating step of drug development, but a single model capable of covering all designing aspects remains to be elucidated. Hence, we developed a drug design modeling framework that integrates multiple approaches, including machine learning based quantitative structure-activity relationship (QSAR) analysis, 3D-QSAR, Bayesian network, pharmacophore modeling, and structure-based docking algorithm. Restrictions for each model were defined for improved individual and overall accuracy. An integration method was applied to join the results from each model to minimize bias and errors. In addition, the integrated model adopts both static and dynamic analysis to validate the intermolecular stabilities of the receptor-ligand conformation. The proposed protocol was applied to identifying HER2 inhibitors from traditional Chinese medicine (TCM) as an example for validating our new protocol. Eight potent leads were identified from six TCM sources. A joint validation system comprised of comparative molecular field analysis, comparative molecular similarity indices analysis, and molecular dynamics simulation further characterized the candidates into three potential binding conformations and validated the binding stability of each protein-ligand complex. The ligand pathway was also performed to predict the ligand "in" and "exit" from the binding site. In summary, we propose a novel systematic CADD methodology for the identification, analysis, and characterization of drug-like candidates. PMID:23651478

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

    ERIC Educational Resources Information Center

    Ngoh, Lucy N.; Shepherd, Marvin D.

    1997-01-01

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

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

    PubMed Central

    Douguet, Dominique

    2010-01-01

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

  13. 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

  14. Drug abuse first aid

    MedlinePlus

    Drug abuse is the misuse or overuse of any medication or drug, including alcohol. This article discusses first ... use of these drugs is a form of drug abuse. Legitimate medications can be abused by people who ...

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

    PubMed

    Hartshorn, Michael J

    2002-12-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Drug abuse first aid

    MedlinePlus

    ... or extremely dry, hot skin Tremors Unconsciousness ( coma ) Violent or aggressive behavior Drug withdrawal symptoms also vary ... jeopardize your own safety. Some drugs can cause violent and unpredictable behavior. Call for professional assistance. Do ...

  19. 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. PMID:26510622

  20. Computer-aided drug discovery

    PubMed Central

    Bajorath, Jürgen

    2015-01-01

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

  1. 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.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Non-Bisphosphonate Inhibitors of Isoprenoid Biosynthesis Identified via Computer-Aided Drug Design

    PubMed Central

    Durrant, Jacob D; Cao, Rong; Gorfe, Alemayehu A; Zhu, Wei; Li, Jikun; Sankovsky, Anna; Oldfield, Eric; McCammon, J Andrew

    2011-01-01

    The relaxed complex scheme, a virtual-screening methodology that accounts for protein receptor flexibility, was used to identify a low-micromolar, non-bisphosphonate inhibitor of farnesyl diphosphate synthase. Serendipitously, we also found that several predicted farnesyl diphosphate synthase inhibitors were low-micromolar inhibitors of undecaprenyl diphosphate synthase. These results are of interest because farnesyl diphosphate synthase inhibitors are being pursued as both anti-infective and anticancer agents, and undecaprenyl diphosphate synthase inhibitors are antibacterial drug leads. PMID:21696546

  5. Computer Aided Engineering Design

    NASA Astrophysics Data System (ADS)

    Saxena, Anupam; Sahay, Birendra

    This book amalgamates geometric modelling, analysis and optimization, the three important aspects in Computer Aided Engineering Design. While the three subjects are well developed by themselves, a detailed discussion on engineering visualization (transformations and projections) and mathematical background of free form, parametric and piecewise design of curves and surfaces is provided. A topological basis is given when discussing wireframe, boundary representation and constructive solid geometry as solid modelling techniques. http://www.springeronline.com/alert/article?a=3D1_1fva7w_9hjul_18j_6

  6. A pocket aide-memoire on drug interactions.

    PubMed

    Stockley, I H

    1975-04-01

    A pocket size "slide-rule" type device designed to be used by physicians, pharmacists and nurses as a memory aid on potential drug-drug interactions is described. Color-coded symbols on the device indicate both the type and clinical significance of the potential interactions involving 56 drugs or groups of drugs. PMID:1130413

  7. Control of HIV/AIDS infection system with drug dosages design via robust H(∞) fuzzy controller.

    PubMed

    Assawinchaichote, Wudhichai

    2015-01-01

    The designing of H∞ fuzzy controller for HIV/AIDS infected dynamic system has been considered in this paper. With TS fuzzy model and LMIs approach, the proposed controller is obtained for such a system. A set of sufficient conditions of the H∞ controller is given to ensure the closed-loop system asymptotic stability and the prescribed H∞ performance level. Finally, the effectiveness of the fuzzy controller design approach is finally presented through the simulation results. PMID:26405968

  8. Drug Convictions May Affect Your Student Aid.

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

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

  9. 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.

  10. Evaluation, by a statistically designed experiment, of an experimental grade of microcrystalline cellulose, Avicel 955, as a technology to aid the production of pellets with high drug loading.

    PubMed

    Jover, I; Podczeck, F; Newton, M

    1996-07-01

    A statistically designed experiment has been undertaken to evaluate an experimental grade of microcrystalline cellulose (Avicel 955) as a technology to aid the production of pellets by extrusion spheronization of formulations with high drug load. An attempt has been made to relate the properties of the drugs to the ability to produce spherical pellets which have a narrow size distribution and are round, as assessed by a 2-dimensional shape factor by the process of extrusion/spheronization. Twenty drugs were tested at a level of 80%, and in all cases pellets could be produced. In some cases in terms of either size distribution or shape they were not of the highest quality. Nevertheless, a best level of water was identified for each drug. Principal component analysis did allow structuring of the data characterizing the process and the pellets, identifying a relationship between the water content and the steady state extrusion force as one component with the median pellet size and its interquartile range as the other. When multivariate analysis was used with the whole data set, it was not possible to relate the drug properties of pKa, freezing point depression, or solubility to the water content, steady state extrusion force, median pellet diameter, its interquartile range, and its shape satisfactorily. Thus other properties of the drug must be involved in the extrusion/spheronization process. Prediction of the best water content to use in a formulation was possible for 50% of the formulations by using a nonlinear model to relate the above drug properties to the water content. PMID:8818993

  11. 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.

  12. Computer-Aided Design (CAD).

    ERIC Educational Resources Information Center

    Burns, William E.

    1986-01-01

    Discusses the field of computer-aided design, which combines the skills and creativity of the architect, designer, drafter, and engineer with the power of the computer. Reports on job tasks, applications, background of the field, job outlook, and necessary training. (CH)

  13. 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.

  14. Can AIDS drugs be afforded?

    PubMed

    1997-11-01

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

  15. Echelle spectrograph software design aid

    NASA Technical Reports Server (NTRS)

    Dantzler, A. A.

    1985-01-01

    A method for mapping, to first order, the spectrograms that result from echelle spectrographic systems is discussed. An in-depth description of the principles behind the method are given so that software may be generated. Such software is an invaluable echelle spectrograph design aid. Results from two applications are discussed.

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

    PubMed

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

    2016-08-01

    Rapidly multiplying cancer cells synthesize greater amounts of cholesterol to build their membranes. Cholesterol-lowering drugs (statins) are currently in clinical trials for anticancer chemotherapy. However, given at higher doses, statins cause serious side effects by inhibiting the formation of other biologically important molecules derived from mevalonate. Sterol 14α-demethylase (CYP51), which acts 10 steps downstream, is potentially a more specific drug target because this portion of the pathway is fully committed to cholesterol production. However, screening a variety of commercial and experimental inhibitors of microbial CYP51 orthologs revealed that most of them (including all clinical antifungals) weakly inhibit human CYP51 activity, even if they display high apparent spectral binding affinity. Only one relatively potent compound, (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VFV), was identified. VFV has been further tested in cellular experiments and found to decrease proliferation of different cancer cell types. The crystal structures of human CYP51-VFV complexes (2.0 and 2.5 Å) both display a 2:1 inhibitor/enzyme stoichiometry, provide molecular insights regarding a broader substrate profile, faster catalysis, and weaker susceptibility of human CYP51 to inhibition, and outline directions for the development of more potent inhibitors. PMID:27313059

  17. Current insights into computer-aided immunotherapeutic design strategies.

    PubMed

    Cai, Zhi; Zhang, Guoyin; Zhang, Xuejin; Liu, Yan; Fu, Xiaojing

    2015-09-01

    Drug designing costs as well as design of immunotherapeutic agents could be nearly halved through the involvement of computer-aided drug designing methods in discovery and research. The inter-disciplinary, time-, and money-consuming process of drug discovery is amended by the development of drug designing, the technique of creating or finding a molecule that can render stimulatory or inhibitory activity upon various biological organisms. Meanwhile, the advancements made within this scientific domain in the last couple of decades have significantly modified and affected the way new bioactive molecules have been produced by the pharmaceutical industry. In this regard, improvements made in hardware solutions and computational techniques along with their efficient integration with biological processes have revolutionized the in silico methods in speeding up the lead identification and optimization processes. In this review, we will discuss various methods of recent computer-aided drug designing techniques that forms the basis of modern day drug discovery projects. PMID:26091813

  18. Synthesis, Biological Evaluation, and Computer-Aided Drug Designing of New Derivatives of Hyperactive Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitors.

    PubMed

    Zhang, Song; Huang, Weibin; Li, Xiaonan; Yang, Zhicheng; Feng, Binghong

    2015-10-01

    The synthesis and biological evaluation of a novel series of compounds based on suberoylanilide hydroxamic acid (SAHA) had been designed as potential histone deacetylase inhibitors (HDACis). Molecular docking studies indicated that our derivatives had better fitting in the binding sites of HDAC8 than SAHA. Compounds 1-5 were synthesized through the synthetic routes. In biological test, compounds also showed good inhibitory activity in HDAC enzyme assay and more potent growth inhibition in human glioma cell lines (MGR2, U251, and U373). A representative compound, N3F, exhibited better inhibitory effect (HDAC, IC50  = 0.1187 μm; U251, IC50  = 0.8949 μm) and lower toxicity for human normal cells (LO2, IC50  = 172.5 μm and MRC5, IC50  = 213.6 μm) compared with SAHA (HDAC, IC50  = 0.8717 μm; U251, IC50  = 8.938 μm; LO2, IC50  = 86.52 μm and MRC5, IC50  = 81.02 μm). In addition, N3F obviously increased Beclin-1 and Caspase-3 and 9 as well as inhibited Bcl-2 in U251 cells. All of our results indicated that these SAHA cap derivatives could serve as potential lead compounds for further optimization. In addition, N3F and N2E both displayed promising profile as antitumor candidates for the treatment of human glioma. PMID:25763653

  19. 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.

  20. 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.

  1. [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. PMID:22710853

  2. 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…

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

    PubMed Central

    Mathers, Bradley M.; Degenhardt, Louisa

    2014-01-01

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

  4. 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)

  5. Purchasing Computer-Aided Design Software.

    ERIC Educational Resources Information Center

    Smith, Roger A.

    1992-01-01

    Presents a model for the purchase of computer-aided design (CAD) software: collect general information, observe CAD in use, arrange onsite demonstrations, select CAD software and hardware, and choose a vendor. (JOW)

  6. [New pediatric drug dosage aids : Improving patient safety].

    PubMed

    Strauß, J M

    2016-03-01

    Dosing errors when administering medicine to children occur often and are due, e.g., to the commonly required dilution of the drugs, misjudgment of the patient's weight, confusion between drugs with similar names, and inadequate communication. Various aids (e.g., measuring tapes and dilution tables) have been designed to avoid mistakes to the greatest extent possible. In daily clinical practice, books and pocket cards are still used for rapid orientation. Use of smartphone-based apps continues to increase, whereby the user is ultimately responsible for their validity. In clinical practice, the simplest possible strategies should be used. A culture that encourages disclosure of errors is useful in order to optimize processes and avoid future errors. PMID:26459455

  7. 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.

  8. 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.

  9. 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.

  10. Poverty, drug abuse fuel Caribbean AIDS outbreak.

    PubMed

    Kovaleski, S F

    1998-01-01

    Hatred and fear of homosexuals, together with a fear of losing tourism revenue, drove many high-level policymakers in the Caribbean to ignore the HIV/AIDS in its infancy. With an annual incidence rate of at least 146.6 people per 100,000, the Bahamas now has one of the highest AIDS rates in the world and the highest such rate in the English-speaking Caribbean. AIDS has become the major cause of death for men and women aged 20-44 in the Bahamas. Indeed, throughout the Caribbean, countries like the Bahamas must now cope with a growing AIDS epidemic. UN AIDS Program figures indicate that at least 310,000 people in the Caribbean have either HIV infection or AIDS, and that the prevalence rate among adults is almost 2%. This compares with an estimated 7.4% of the adult population of sub-Saharan Africa which is infected and 0.6% of adults in North America. 65% of reported AIDS cases in the region result from heterosexual intercourse. While the annual number of AIDS cases has been falling in North America over the last several years and rates in Latin America have leveled off, rates in the Caribbean are increasing sharply. Poverty, the population's lack of awareness, low levels of education, internal and international migration, crack cocaine use, promiscuity, high levels of STDs, prostitution, and tourism are also facilitating the spread of HIV in the Caribbean. Social conservatism, mainly in the English-Caribbean, about discussing sex impedes the implementation and success of HIV/AIDS prevention interventions. PMID:12293303

  11. 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.

  12. 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. PMID:16354561

  13. Scaled Ellipses For Computer-Aided Design

    NASA Technical Reports Server (NTRS)

    Schembri, Anthony J.

    1990-01-01

    An addition to CAD-PACK, computer-aided design program, speeds preparation of iosmetric drawings, particularly cutaway views showing bores and threads. Consists of set of 50 scaled ellipses on detail pages of program. Designer selects ellipse, rotates it, and draws feature. Then erases reference lines on video screen.

  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. 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.

  16. Drug Use and AIDS Risk in a Soup Kitchen Population.

    ERIC Educational Resources Information Center

    Schilling, Robert F.; And Others

    1992-01-01

    Interviewed 148 drug users in urban soup kitchen. Focused on subjects' risk-taking and risk-reduction behavior related to injection drug use, perceived changes in risk behavior, perceived risk for contracting Acquired Immune Deficiency Syndrome (AIDS), and socioeconomic and attitudinal correlates of injecting and sharing needles. Findings…

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

    PubMed

    Kaur, S R

    1996-01-01

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

  18. 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…

  19. Teaching Computer Aided Architectural Design at UCLA.

    ERIC Educational Resources Information Center

    Mitchell, William J.

    This brief overview includes a rationale for the program and describes course goals and objectives, curriculum content, teaching methods and materials, staffing, and problems of integrating computer aided design with traditional architectural curricula at the School of Architecture and Urban Planning at UCLA. A list of texts for use in teaching…

  20. COMPUTER AIDED DESIGN OF DIFFUSED AERATION SYSTEMS

    EPA Science Inventory

    CADDAS (Computer Aided Design of Diffused Aeration Systems) is a microcomputer-based program that analyzes the cost and performance of diffused aeration used in activated sludge wastewater treatment systems. The program can analyze both coarse bubble and fine pore diffusers as we...

  1. Simulation as an Aid to Experimental Design.

    ERIC Educational Resources Information Center

    Frazer, Jack W.; And Others

    1983-01-01

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

  2. Computer Code Aids Design Of Wings

    NASA Technical Reports Server (NTRS)

    Carlson, Harry W.; Darden, Christine M.

    1993-01-01

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

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. Arthritis Genetics Analysis Aids Drug Discovery

    MedlinePlus

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

  8. 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

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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. 333.150 Section 333.150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products §...

  14. 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.

  15. Geometric modeling for computer aided design

    NASA Technical Reports Server (NTRS)

    Schwing, James L.

    1993-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    Code of Federal Regulations, 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.”...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  20. 21 CFR 344.52 - Labeling of ear drying 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 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.”...

  1. 21 CFR 344.52 - Labeling of ear drying 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 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.”...

  2. 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.”...

  3. Domain specific software design for decision aiding

    NASA Technical Reports Server (NTRS)

    Keller, Kirby; Stanley, Kevin

    1992-01-01

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

  4. 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.

  5. 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.

  6. Physiological modeling for hearing aid design

    NASA Astrophysics Data System (ADS)

    Bruce, Ian C.; Young, Eric D.; Sachs, Murray B.

    2002-05-01

    Physiological data from hearing-impaired cats suggest that conventional hearing aid signal-processing schemes do not restore normal auditory-nerve responses to a vowel [Miller et al., J. Acoust. Soc. Am. 101, 3602 (1997)] and can even produce anomalous and potentially confounding patterns of activity [Schilling et al., Hear. Res. 117, 57 (1998)]. These deficits in the neural representation may account at least partially for poor speech perception in some hearing aid users. An amplification scheme has been developed that produces neural responses to a vowel more like those seen in normal cats and that reduces confounding responses [Miller et al., J. Acoust. Soc. Am. 106, 2693 (1999)]. A physiologically accurate model of the normal and impaired auditory periphery would provide simpler and quicker testing of such potential hearing aid designs. Details of such a model, based on that of Zhang et al. [J. Acoust. Soc. Am. 109, 648 (2001)], will be presented. Model predictions suggest that impairment of both outer- and inner-hair cells contribute to the degraded representation of vowels in hearing-impaired cats. The model is currently being used to develop and test a generalization of the Miller et al. speech-processing algorithm described above to running speech. [Work supported by NIDCD Grants DC00109 and DC00023.] a)Now with the Dept. of Electrical and Computer Engineering, McMaster Univ., 1280 Main St. W., Hamilton, ON L8S 4K1, Canada.

  7. Tattoo designs among drug abusers.

    PubMed

    Borokhov, Alexander; Bastiaans, Roland; Lerner, Vladimir

    2006-01-01

    Forty-one males with drug abuse who had tattoos with designs related to drug use were selected from a larger sample of tattooed males in forensic psychiatric wards, prisons and military recruitment centers during the period 1986-2000 in the former Soviet Union. Two-thirds of the tattoo images were related to a specific drug, some served to hide signs of repeated drug use, others to identify ideal sites for injection. Knowledge of these details may be helpful to clinicians, although images may be influenced by current trends. PMID:16910382

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

    PubMed Central

    Amon, Joseph J

    2008-01-01

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

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

    PubMed

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

    1992-10-01

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

  10. Latest trends in drugs of abuse - HIV infection and neuroAIDS.

    PubMed

    Tiwari, Sneham; Nair, Madhavan Pn; Saxena, Shailendra K

    2013-02-01

    Drug abuse and co-occurring infections are associated with significant morbidity and mortality. In particular, HIV infection is associated with serious neurological complications, including neuroAIDS. Therefore, on 13-15 September 2012, the OMICS Group (USA) and Shailendra K Saxena (Centre for Cellular and Molecular Biology, India) hosted a symposium titled: 'Drugs of Abuse - HIV Infection and NeuroAIDS: A Global Perspective' that was cochaired by Jag H Khalsa and Jeymohan Joseph of the NIH, MD, USA, at the 3rd World Congress on Biotechnology, in Hyderabad, India. Renowned scientists from India and the USA highlighted a number of issues, including the epidemiology, causes and underlying pathophysiological mechanisms of neuroAIDS, impact on health, and designing new treatment modalities (e.g., nanotherapeutics) for the treatment of neurological disorders. PMID:23626655

  11. Substance abuse: the designer drugs.

    PubMed

    Beebe, D K; Walley, E

    1991-05-01

    Designer drugs, chemically altered compounds derived from federally controlled substances, have become a major cause of addiction and overdose deaths. These drugs include mescaline analogs, synthetic opioids, arylhexylamines, methaqualone derivatives and crack, a new form of cocaine. Sudden changes in mood, weight loss, depression, disturbed sleep patterns, deteriorating school or work performance, marital problems, and loss of interest in friends and social activities may be signs of drug addiction. Life-threatening complications of acute intoxication, such as hyperthermia, seizures, combative and psychotic behavior, and cardiorespiratory collapse, require prompt diagnosis and supportive intervention. PMID:2021104

  12. Simulation as an aid to experimental design

    SciTech Connect

    Frazer, J.W.; Balaban, D.J.; Wang, J.L.

    1983-05-01

    A simulator of chemical reactions can aid the scientist in the design of experimentation. They are of great value when studying enzymatic kinetic reactions. One such simulator is a numerical ordinary differential equation solver which uses interactive graphics to provide the user with the capability to simulate an extremely wide range of enzyme reaction conditions for many types of single substrate reactions. The concentration vs. time profiles of any subset or all nine states of a complex reaction can be displayed with and without simulated instrumental noise. Thus the user can estimate the practicality of any proposed experimentation given known instrumental noise. The experimenter can readily determine which state provides the most information related to the proposed kinetic parameters and mechanism. A general discussion of the program including the nondimensionalization of the set of differential equations is included. Finally, several simulation examples are shown and the results discussed.

  13. 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.

  14. 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 ...

  15. 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.

  16. 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,…

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

    PubMed

    Woltosz, Walter S

    2012-01-01

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

  18. 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. 338.50 Section 338.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime...

  19. 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. PMID:25800654

  20. Computer-aided design for metabolic engineering.

    PubMed

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

    2014-12-20

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

  1. Design Aids for Real-Time Systems (DARTS)

    NASA Technical Reports Server (NTRS)

    Szulewski, P. A.

    1982-01-01

    Design-Aids for Real-Time Systems (DARTS) is a tool that assists in defining embedded computer systems through tree structured graphics, military standard documentation support, and various analyses including automated Software Science parameter counting and metrics calculation. These analyses provide both static and dynamic design quality feedback which can potentially aid in producing efficient, high quality software systems.

  2. 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.

  3. 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.

  4. Structure-Based Strategies for Drug Design and Discovery

    NASA Astrophysics Data System (ADS)

    Kuntz, Irwin D.

    1992-08-01

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

  5. 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

  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. PMID:25860175

  7. 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

  8. 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.

  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. PMID:24146385

  10. Designer drugs: the evolving science of drug discovery.

    PubMed

    Wanke, L A; DuBose, R F

    1998-07-01

    Drug discovery and design are fundamental to drug development. Until recently, most drugs were discovered through random screening or developed through molecular modification. New technologies are revolutionizing this phase of drug development. Rational drug design, using powerful computers and computational chemistry and employing X-ray crystallography, nuclear magnetic resonance spectroscopy, and three-dimensional quantitative structure activity relationship analysis, is creating highly specific, biologically active molecules by virtual reality modeling. Sophisticated screening technologies are eliminating all but the most active lead compounds. These new technologies promise more efficacious, safe, and cost-effective medications, while minimizing drug development time and maximizing profits. PMID:10185235

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

    PubMed

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

    2016-09-01

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

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

    ERIC Educational Resources Information Center

    Fitzpatrick, F. J.; And Others

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

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

    PubMed

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

    2008-01-01

    This paper analyzes the interrelationships between the stigma of HIV/AIDS stigma and the co-stigmas of commercial sex (CS) and injecting drug use (IDU). Students of a Bangkok nursing college (N=144) were presented with vignettes describing a person varying in the disease diagnoses (AIDS, leukemia, no disease) and co-characteristics (IDU, CS, blood transfusion, no co-characteristic). For each vignette, participants completed a social distance measure assessing their attitudes towards the hypothetical person portrayed. Multivariate analyses showed strong interactions between the stigmas of AIDS and IDU but not between AIDS and CS. Although AIDS was shown to be stigmatizing in and of itself, it was significantly less stigmatizing than IDU. The findings highlight the need to consider the non-disease-related stigmas associated with HIV as well as the actual stigma of HIV/AIDS in treatment and care settings. Methodological strengths and limitations were evaluated and implications for future research discussed. PMID:17364148

  14. Fragment-based drug design.

    PubMed

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

    2011-01-01

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

  15. 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).

  16. 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.

  17. School District Uses Computer Aided Design and Drafting.

    ERIC Educational Resources Information Center

    Lorentz, Gordon S.

    1988-01-01

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

  18. Molecular Similarity in Computer-Aided Molecular Design.

    NASA Astrophysics Data System (ADS)

    Hodgkin, Edward E.

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

  19. User interface for integrated computer aided design systems

    NASA Technical Reports Server (NTRS)

    Schwing, James L.

    1986-01-01

    The purpose was the development of a user interface and other appropriate tools to be used in Computer Aided Design systems which can integrate a wide variety of independently developed design and analysis tools. The interface was intended for the integration of programs to be used in the conceptual design of aerospace systems. A user's manual is included.

  20. 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.

  1. MOBIC: Designing a Travel Aid for Blind and Elderly People

    NASA Astrophysics Data System (ADS)

    Petrie, Helen; Johnson, Valerie; Strothotte, Thomas; Raab, Andreas; Fritz, Steffi; Michel, Rainer

    This paper presents the research for the development of a new travel aid to increase the independent mobility of blind and elderly travellers. This aid will build on the technologies of geographical information systems (GIS) and the Global Positioning System (GPS). The MOBIC Travel Aid (MOTA) consists of two interrelated components: the MOBIC Pre-journey System (MOPS) to assist users in planning journeys and the MOBIC Outdoor System (MOODS) to execute these plans by providing users with orientation and navigation assistance during journeys. The MOBIC travel aid is complementary to primary mobility aids such as the long cane or guide dog. Results of a study of user requirements are presented and their implications for the initial design of the system are discussed.

  2. Improving Outcomes in State AIDS Drug Assistance Programs

    PubMed Central

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

    2009-01-01

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

  3. 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.

  4. Interactive graphical computer-aided design system

    NASA Technical Reports Server (NTRS)

    Edge, T. M.

    1975-01-01

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

  5. 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.

  6. 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.

  7. Anticipating designer drug-resistant cancer cells.

    PubMed

    Frangione, Mark L; Lockhart, John H; Morton, Daniel T; Pava, Libia M; Blanck, George

    2015-07-01

    Successful use of anticancer designer drugs is likely to depend on simultaneous combinations of these drugs to minimize the development of resistant cancer cells. Considering the knowledge base of cancer signaling pathways, mechanisms of designer drug resistance should be anticipated, and early clinical trials could be designed to include arms that combine new drugs specifically with currently US Food and Drug Administration (FDA)-approved drugs expected to blunt alternative signaling pathways. In this review, we indicate examples of alternative signal pathways for recent anticancer drugs, and the use of original, Python-based software to systematically identify signaling pathways that could facilitate resistance to drugs targeting a particular protein. Pathway alternatives can be assessed at http://www.alternativesignalingpathways.com, developed with this review article. PMID:25697478

  8. A machine learning approach to computer-aided molecular design.

    PubMed

    Bolis, G; Di Pace, L; Fabrocini, F

    1991-12-01

    Preliminary results of a machine learning application concerning computer-aided molecular design applied to drug discovery are presented. The artificial intelligence techniques of machine learning use a sample of active and inactive compounds, which is viewed as a set of positive and negative examples, to allow the induction of a molecular model characterizing the interaction between the compounds and a target molecule. The algorithm is based on a twofold phase. In the first one--the specialization step--the program identifies a number of active/inactive pairs of compounds which appear to be the most useful in order to make the learning process as effective as possible and generates a dictionary of molecular fragments, deemed to be responsible for the activity of the compounds. In the second phase--the generalization step--the fragments thus generated are combined and generalized in order to select the most plausible hypothesis with respect to the sample of compounds. A knowledge base concerning physical and chemical properties is utilized during the inductive process. PMID:1818094

  9. 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)

  10. 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.

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

    PubMed

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

    1991-01-01

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

  12. Memory interface simulator: A computer design aid

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  13. 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,…

  14. Computer Aided Design in the Classroom.

    ERIC Educational Resources Information Center

    Duelm, Brian Lee

    Estimates calling for 1.2 million computer-assisted design (CAD) operator positions to be available by 1990 have prompted educational institutions throughout the country to incorporate instruction in CAD into their industrial arts curricula. Therefore, the question for schools is not whether to buy but rather what to buy. An effective strategy for…

  15. Computer aided design study of hypermixing nozzles

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

  16. Computer-aided surface representation and design

    NASA Technical Reports Server (NTRS)

    Barnhill, R. E.

    1984-01-01

    New methods for representing and approximating three and four dimensional surfaces were created. These schemes are the core of our forthcoming Surface Software Package. Surfaces are understood adequately only through the use of dynamic computer graphics; therefore, graphics capability is also included. The numerous applications of surface methods include modeling physical phenomena (e.g., combustion) and designing objects (e.g., airplanes and cars).

  17. Participatory design for drug-drug interaction alerts.

    PubMed

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

    2015-01-01

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

  18. Computer-Aided Design Of Sheet-Material Parts

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

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

    PubMed

    Elliott, Richard

    2004-12-01

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

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  1. On-Line Authoring Aids for Instructional Design.

    ERIC Educational Resources Information Center

    Schulz, Russel E.; And Others

    Since the usefulness of the Interservice Procedures for Instructional Systems Development (IPISD) depends on authoring aids which enable personnel to translate IPISD procedures into instructional products, this project examined the feasibility of providing such "how to do it" guidance for the instructional design and development tasks identified…

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

    ERIC Educational Resources Information Center

    National Coalition for Advanced Manufacturing, Washington, DC.

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

  3. 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)

  4. 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.

  5. Computer-aided design of flight control systems

    NASA Technical Reports Server (NTRS)

    Stengel, Robert F.; Sircar, Subrata

    1991-01-01

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

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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.

  11. Thermodynamic Studies for Drug Design and Screening

    PubMed Central

    Garbett, Nichola C.; Chaires, Jonathan B.

    2012-01-01

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

  12. 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

  13. 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

  14. 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…

  15. 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.…

  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. Program Aids Design Of Fluid-Circulating Systems

    NASA Technical Reports Server (NTRS)

    Bacskay, Allen; Dalee, Robert

    1992-01-01

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

  18. Computer aided design of multi-phase switched reluctance motor

    NASA Astrophysics Data System (ADS)

    Sheth, N. K.; Rajagopal, K. R.

    2005-05-01

    In this paper, a comprehensive computer-aided design (CAD) procedure of multiphase switched reluctance motor (SRM) is presented. Better approach for calculation of the outer dimensions, phase inductance, flux linkage and losses, and also a different concept for calculating the average torque of the motor are incorporated in the CAD program. The average torque is calculated based on the most effective 15° (for 8/6 SRM) of the static torque profile of the motor. A sample design of a 5hp SRM is presented in detail and the design is validated by conducting a two-dimensional finite element analysis of the motor.

  19. 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.

  20. Collaborative prototyping approaches for ICU decision aid design.

    PubMed

    Ehrhart, L S; Hanson, C W; Marshall, B E; Marshall, C; Medsker, C

    1999-01-01

    When computer-based aids do not support the human users' decision-making strategies or anticipate the organizational impacts of technological change, advances in information technology may degrade rather than enhance decision-making performance. Such failures suggest the design of human-computer cooperation for problem solving and decision-making must be driven by human cognitive and organizational process requirements rather than computer technology. Decision- and user-centered development techniques involve domain experts and end-users in the earliest phases of design to evolve an understanding of requirements through iterative prototyping. This paper presents a collaborative approach to cognitive systems engineering applied to developing a clinical aid to assist respiratory care in the surgical ICU. PMID:10566460

  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. Demographic characteristics, drug use, and sexual behavior of i.v. drug user with AIDS in Bronx, New York.

    PubMed Central

    Schrager, L; Friedland, G; Feiner, C; Kahl, P

    1991-01-01

    Intravenous (i.v.) drug users are a key factor in the transmission of human immunodeficiency virus (HIV) infection, yet epidemiologic information about this population, especially those with acquired immunodeficiency syndrome, is scarce. The demographic characteristics, drug use behavior, and sexual practices of i.v. drug users who developed AIDS were prospectively studied at the Montefiore Medical Center from October 1984 to February 1988. The early wave of i.v. drug users with AIDS was characterized by poverty, minority overrepresentation (more than 80 percent were black or Hispanic), and initiation of i.v. drug use at an early age (median age 19 years). Injection of drugs and sharing of needles was frequent. Most had used so-called shooting galleries, but only for a minority of injection episodes. Heroin or cocaine use was almost universal, nearly always accompanied by abuse of another substance, usually alcohol or marijuana. Fewer than a third had ever participated in a methadone maintenance program, but more than 40 percent had been in prison since 1978. All patients had been sexually active, often with partners who were not i.v. drug users. The research suggests a complex interaction existing between high-risk demographic characteristics, drug use practice, and certain types of sexual behavior, all of which contributed to the early spread of HIV infection in this population. Efforts that are directed toward interrupting i.v. drug user-related transmission of HIV need to include consideration of these characteristics. PMID:1899944

  3. Computer-aided design of antenna structures and components

    NASA Technical Reports Server (NTRS)

    Levy, R.

    1976-01-01

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

  4. 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.

  5. HIV/AIDS and Drug Abuse: Intertwined Epidemics

    MedlinePlus

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

  6. A computer aided design procedure for generating gear teeth

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

    A procedure for computer aided design (CAD) of gear teeth is presented. It is developed for generated teeth fabricated by a hob cutter or a shaper. It provides a means for analytically and numerically determining the tooth profile, given the cutter profile. An illustrative example with involute tooth profiles is given. Application with non-standard profiles and with bevel, spiral bevel, and hypoid gears is discussed.

  7. Computer-Aided Design of a Sulfate Encapsulating Receptor

    SciTech Connect

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

    2009-01-01

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

  8. 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.

  9. 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

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

    PubMed

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

    2016-04-25

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

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

    PubMed

    Christakis, N A

    1988-01-01

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

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

    PubMed Central

    Zhao, Min; Ling, Walter

    2014-01-01

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

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

    PubMed Central

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

    1989-01-01

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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  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. 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

  20. 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.

  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. 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.

  3. 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

  4. 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.

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

    PubMed

    John, P A

    1988-03-01

    Many manufacturing companies have now awakened to the significance of computer aided design (CAD), although the majority of them have only been able to purchase computerised draughting systems of which only a subset produce direct manufacturing data. Such companies are moving steadily towards the concept of computer integrated manufacture (CIM), and this demands CAD to address more than draughting. CAD architects are thus having to rethink the basic specification of such systems, although they typically suffer from an insufficient understanding of the design task and have consequently been working with inadequate specifications. It is at this fundamental level that ergonomics has much to offer, making its contribution by encouraging user-centred design. The discussion considers the relationships between CAD and: the design task; the organisation and people; creativity; and artificial intelligence. It finishes with a summary of the contribution of ergonomics. PMID:15676646

  6. 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.

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

    PubMed

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

    2016-01-01

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

  8. 75 FR 53973 - Guidance for Industry; Small Entities Compliance Guide-Designation of New Animal Drugs for Minor...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ... requirements of the final rule published in the Federal Register of July 26, 2007 (72 FR 41010). FDA has...-- Designation of New Animal Drugs for Minor Uses or Minor Species; Availability AGENCY: Food and Drug... Animal Drugs for Minor Uses or Minor Species.'' This small entities compliance guide (SECG) aids...

  9. Evaluation of an AIDS education model for women drug users in jail.

    PubMed

    Magura, S; Kang, S Y; Shapiro, J L; O'Day, J

    1995-02-01

    This paper reports outcome evaluation results of an AIDS education program for drug-using women in jail, of whom the majority were current drug injectors, had high-risk sexual partners, and never used condoms for insertive sex. The women participated in four small-group health/HIV education sessions. Education participants and controls were followed-up 7 months after their release from jail; the two groups did not differ significantly on drug- or sex-related HIV risk behaviors at follow-up. However, being in drug dependency treatment (primarily methadone maintenance) at follow-up was associated with reduced heroin use, crack use, drug dealing, and criminal activity. Although improved HIV education in jail is important, better networks of community resources, including more accessible community drug dependency treatment, also must be developed to support drug-dependent women after their release from jail. PMID:7790127

  10. 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...

  11. 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  13. 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...

  14. Designer drugs 2015: assessment and management.

    PubMed

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

    2015-01-01

    Recent designer drugs, also known as "legal highs," include substituted cathinones (e.g., mephedrone, methylone, and methylenedioxypyrovalerone, often referred to as "bath salts"); synthetic cannabinoids (SCs; e.g., Spice); and synthetic hallucinogens (25I-NBOMe, or N-bomb). Compound availability has evolved rapidly to evade legal regulation and detection by routine drug testing. Young adults are the primary users, but trends are changing rapidly; use has become popular among members of the military. Acute toxicity is common and often manifests with a constellation of psychiatric and medical effects, which may be severe (e.g., anxiety, agitation, psychosis, and tachycardia), and multiple deaths have been reported with each of these types of designer drugs. Clinicians should keep designer drugs in mind when evaluating substance use in young adults or in anyone presenting with acute neuropsychiatric complaints. Treatment of acute intoxication involves supportive care targeting manifesting signs and symptoms. Long-term treatment of designer drug use disorder can be challenging and is complicated by a lack of evidence to guide treatment. PMID:25928069

  15. Defining Patient Centric Pharmaceutical Drug Product Design.

    PubMed

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

    2016-09-01

    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved. PMID:27317470

  16. 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. PMID:22287994

  17. 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

  18. 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)…

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

    PubMed

    Gupta, Umesh; Jain, Narendra K

    2010-03-18

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

  20. 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.

  1. 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.

  2. Computer aided design and analysis of gear tooth geometry

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

  3. 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.

  4. 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.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Shelate, Pragna; Dave, Divyang

    2016-01-01

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

  7. 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.

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

    PubMed

    Calamia, J R

    1996-01-01

    Although the development of computer-aided design (CAD) and computer-aided manufacture (CAM) technology and the benefits of increased productivity became obvious in the automobile and aerospace industries in the 1970s, investigations of this technology's application in the field of dentistry did not begin until the 1980s. Only now are we beginning to see the fruits of this work with the commercial availability of some systems; the potential for this technology seems boundless. This article reviews the recent literature with emphasis on the period from June 1992 to May 1993. This review should familiarize the reader with some of the latest developments in this technology, including a brief description of some systems currently available and the clinical and economical rationale for their acceptance into the dental mainstream. This article concentrates on a particular system, the Cerec (Siemens/Pelton and Crane, Charlotte, NC) system, for three reasons: First, this system has been available since 1985 and, as a result, has a track record of almost 7 years of data. Most of the data have just recently been released and consequently, much of this year's literature on CAD-CAM is monopolized by studies using this system. Second, this system was developed as a mobile, affordable, direct chairside CAD-CAM restorative method. As such, it is of special interest to the patient, providing a one-visit restoration. Third, the author is currently engaged in research using this particular system and has a working knowledge of this system's capabilities. PMID:9462062

  9. 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

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

    PubMed

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

    2015-01-01

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

  11. Computational Thermodynamics Aided High-Entropy Alloy Design

    NASA Astrophysics Data System (ADS)

    Zhang, Chuan; Zhang, Fan; Chen, Shuanglin; Cao, Weisheng

    2012-07-01

    Thermodynamic calculation is used to shed light on the design and development of high-entropy alloys (HEAs) in this article. A thermodynamic database for the Al-Co-Cr-Fe-Ni was developed, and phase diagrams of this system were calculated. The calculated results, such as primary solidified phases, which are fractions of stable phases at a given alloy composition, explain the published experimental observations fairly well for both as-cast and homogenized alloys. These calculations also confirm the effect of each element on the face-centered cubic (fcc)/body-centered cubic (bcc) structure transition as published in the literature. The role of thermodynamic calculation in aiding effective design of HEAs is clearly demonstrated by this work.

  12. An analysis of FDA-approved drugs for infectious disease: HIV/AIDS drugs.

    PubMed

    Kinch, Michael S; Patridge, Eric

    2014-10-01

    HIV/AIDS is one of the worst pandemics in history. According to the World Health Organization, 26 million people have died since 1981 - 1.6 million in 2012 alone. The dramatic rise in HIV/AIDS mobilized a swift and impressive coordination among governmental, academic and private sector organizations to identify the virus and develop new treatments. Herein, we assess the arsenal of 28 new molecular entities (NMEs) targeting HIV/AIDS. These data demonstrate that the first approval of zidovudine presaged an expansion of the antiviral repertoire over the following years. Whereas the rate of HIV/AIDS NMEs is rapidly declining, so is the number of organizations developing NMEs. We speculate that decisions to abandon further research reflect, in part, growing costs and time required for development. PMID:24880109

  13. Computer-aided auditing of prescription drug claims.

    PubMed

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

    2014-09-01

    We describe a methodology for identifying and ranking candidate audit targets from a database of prescription drug claims. The relevant audit targets may include various entities such as prescribers, patients and pharmacies, who exhibit certain statistical behavior indicative of potential fraud and abuse over the prescription claims during a specified period of interest. Our overall approach is consistent with related work in statistical methods for detection of fraud and abuse, but has a relative emphasis on three specific aspects: first, based on the assessment of domain experts, certain focus areas are selected and data elements pertinent to the audit analysis in each focus area are identified; second, specialized statistical models are developed to characterize the normalized baseline behavior in each focus area; and third, statistical hypothesis testing is used to identify entities that diverge significantly from their expected behavior according to the relevant baseline model. The application of this overall methodology to a prescription claims database from a large health plan is considered in detail. PMID:23821344

  14. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    1994-01-01

    This article describes the development of a videotape targeted at persons under supervision of the criminal justice system. The videotape seeks to encourage those who use illicit drugs to enter drug treatment and to motivate those at risk for exposure to human immunodeficiency virus (HIV) to alter behaviors that may transmit infection. The criminal justice system presents an important opportunity to deliver such messages, particularly to a large population of persons briefly detained in a jail or lockup and released without subsequent incarceration. Evidence suggests that, even in this audience, knowledge of how to prevent exposure to HIV is widespread, yet those at risk often fail to take appropriate precautions: motivating behavior change demands more than imparting information. In order to shape this videotape, we analyzed the target audience and developed a drama-based approach that applies the framework of social learning theory, the health belief model, and principles of social marketing. This article describes the integration of that theoretical framework into the production process, content, and strategy of the videotape. PMID:8046547

  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. PMID:24109658

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

    PubMed

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

    2015-11-01

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

  19. 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

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

    NASA Technical Reports Server (NTRS)

    Ramakrishnan, Jayant V.; Singh, Ramen P.

    1989-01-01

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

  1. 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.

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

    SciTech Connect

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

    2004-07-14

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

  3. 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

  4. 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. PMID:8032444

  5. Strategies in the rational drug design.

    PubMed

    Mavromoustakos, T; Durdagi, S; Koukoulitsa, C; Simcic, M; Papadopoulos, M G; Hodoscek, M; Grdadolnik, S Golic

    2011-01-01

    Rational design is applied in the discovery of novel lead drugs. Its rapid development is mainly attributed to the tremendous advancements in the computer science, statistics, molecular biology, biophysics, biochemistry, medicinal chemistry, pharmacokinetics and pharmacodynamics experienced in the last few decades. The promising feature that characterizes the application of rational drug design is that it uses for developing potential leads in drug discovery all known theoretical and experimental knowledge of the system under study. The utilization of the knowledge of the molecular basis of the system ultimately aims to reduce human power cost, time saving and laboratory expenses in the drug discovery. In this review paper various strategies applied for systems which include: (i) absence of knowledge of the receptor active site; (ii) the knowledge of a homology model of a receptor, (iii) the knowledge of the experimentally determined (i.e. X-ray crystallography, NMR spectroscopy) coordinates of the active site of the protein in absence and (iv) the presence of the ligand will be analyzed. PMID:21568895

  6. 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.

  7. 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.

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

    PubMed

    Golchert, D; Bines, E; Carmody, A

    2013-09-10

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

  9. 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

  10. Accessible haptic technology for drug design applications.

    PubMed

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

    2009-02-01

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

  11. 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

  12. From paper drawings to computer-aided design

    NASA Astrophysics Data System (ADS)

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

    1985-02-01

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

  13. Quicklist: The basis for a computer aided logic design system

    NASA Technical Reports Server (NTRS)

    Lushbaugh, W. A.

    1980-01-01

    Quicklist, a preprocessor for an existing wire list program that cuts the description of the wire list by about 67 percent over previous methods, is described. Quicklist uses two different methods to shorten the input data. The first of these is the use of parentheses to allow a compact way of describing signal names which increment (or decrement) by one, i.e., typical signal names in a bus. The other method used is the equal sign. Using this symbol in a signal list says that the rest of the signals on that chip are the same as those on the previous chip described. Quicklist is intended to be the basis of a computer aided logic design system.

  14. 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.

  15. Computer aided microbial safety design of food processes.

    PubMed

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

    1994-12-01

    To reduce the time required for product development, to avoid expensive experimental tests, and to quantify safety risks for fresh products and the consequence of processing there is a growing interest in computer aided food process design. This paper discusses the application of hybrid object-oriented and rule-based expert system technology to represent the data and knowledge of microbial experts and food engineers. Finite element models for heat transfer calculation routines, microbial growth and inactivation models and texture kinetics are combined with food composition data, thermophysical properties, process steps and expert knowledge on type and quantity of microbial contamination. A prototype system has been developed to evaluate changes in food composition, process steps and process parameters on microbiological safety and textual quality of foods. PMID:7703003

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

    ERIC Educational Resources Information Center

    Santiago, Deborah A.

    2013-01-01

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

  17. A Design for a Model College Financial Aid Office.

    ERIC Educational Resources Information Center

    Van Dusen, William D.; O'Hearne, John J.

    This report discusses the current types of financial aid and the principles and practices that guide college financial aid programs. Although specific functions vary among institutions, the authors cite a common core of operational activities; counseling about student expenses and financial aid opportunities, general administration, student…

  18. 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. PMID:25492523

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

    NASA Technical Reports Server (NTRS)

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

    1981-01-01

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

  20. On our failure to face the link between drug use and AIDS.

    PubMed

    Blansfield, H N

    1996-01-01

    It is necessary that society accept the medical, neurological basis of compulsive drug/alcohol use in order for it to get on with finding and using pragmatic approaches to treatment, rather than punishment, as the rational way to deal with these issues. The increased availability of oral methadone must be promoted, not only because it eliminates the need for drug injection, but because it allows the opioid dependent to lead comfortable and functional lives. The emphasis on punishment and incarceration for illicit-drug users or purveyors must give way to alternatives bent on treatment and rehabilitation. More states should follow the example of Connecticut in dealing wisely with drug/AIDS issues. PMID:10915249

  1. Prevention, control and treatment of HIV-AIDS among injecting drug use in Bandung, Indonesia.

    PubMed

    Alisjahbana, Bachti; Susanto, Herman; Roesli, Rully; Yusuf, Hadi; Hinduan, Zahrotur; Mase, Johannes C; Surahman, Eri; van der Ven, Andre

    2009-07-01

    Indonesia is facing a growing HIV-epidemic that in many areas is driven by injecting drug use (IDU). IDUs underutilize health services, partly because of legal aspects which also cause that many are held in prison, where further HIV- transmission may take place. Most HIV-infected patients present with advanced HIV-AIDS and many deaths before starting antiretroviral treatment. The growing HIV-epidemic in Indonesia has socio-economical implications for individual patients as well as for the health system and for society. IMPACT, a multidisciplinary university-based program in Bandung, West-Java, integrates HIV-prevention and treatment, combining research and implementation. Biomedical, public health and sociobehavioral expertise is used for educational programs for adolescents; scaling-up HIV-testing, harm reduction strategies and care for HIV/AIDS in hospital, community and prison; and institutional as well as individual capacity building related to IDU and HIV/AIDS. It is expected that these activities can make a significant contribution to control of HIV-AIDS in the context of injecting drug use in West-Java and Indonesia as a whole. PMID:19920301

  2. AIDS in New York City: the role of intravenous drug users.

    PubMed Central

    Ron, A.; Rogers, D. E.

    1989-01-01

    The key to the future of the HIV epidemic is the intravenous drug user. In New York City the future has arrived--intravenous drug use is now the predominant risk factor among new cases of AIDS. Our limited knowledge of most facets of drug abuse prevention and treatment and the emotional polarity and politicalization of the issues surrounding AIDS have made control of its spread among intravenous drug users very difficult. Clearly new research efforts are needed better to decide how to reduce the further spread of HIV infection among this group. But efforts to stop the spread cannot await these results. Intense and immediate efforts should focus on five areas for potential control of the spread of HIV infection among drug users: education, treatment on demand, expanding support services, providing sterile equipment, and readjustment of some of society's moral judgments that currently block action. Let us hope that in 10 years we do not look back and realize that we did too little too late while it was still possible to make a difference. PMID:2695203

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

    SciTech Connect

    Hay, Benjamin

    2008-01-01

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

  4. USING ASHFORD'S GENERAL MODEL TO AID IN THE UNDERSTANDING OF A PESTICIDE'S NEUROTOXIC EFFECT THROUGH PESTICIDE-DRUG MIXTURE EXPERIMENTS

    EPA Science Inventory

    Ashford's 1981 paper in BIOMETRICS provides a framework for interpreting the joint action of mixtures of drugs. These concepts are applied to the situation in which the mechanism of three drugs are fairly well understood and mixtures of pesticides and drugs are studied to aid in ...

  5. 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

  6. 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

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

    PubMed

    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

  8. Volume of Distribution in Drug Design.

    PubMed

    Smith, Dennis A; Beaumont, Kevin; Maurer, Tristan S; Di, Li

    2015-08-13

    Volume of distribution is one of the most important pharmacokinetic properties of a drug candidate. It is a major determinant of half-life and dosing frequency of a drug. For a similar log P, a basic molecule will tend to exhibit higher volume of distribution than a neutral molecule. Acids often exhibit low volumes of distribution. Although a design strategy against volume of distribution can be advantageous in achieving desirable dosing regimen, it must be well-directed in order to avoid detrimental effects to other important properties. Strategies to increase volume of distribution include adding lipophilicity and introducing basic functional groups in a way that does not increase metabolic clearance. PMID:25799158

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

    PubMed Central

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

    2006-01-01

    Illicit drug abuse and HIV/AIDS have increased rapidly in the past 10 to 20 years in China. This paper reviews drug abuse in China, the HIV/AIDS epidemic and its association with injection drug use (IDU), and Chinese policies on illicit drug abuse and prevention of HIV/AIDS based on published literature and unpublished official data. As a major drug trans-shipment country with source drugs from the "Golden Triangle" and "Gold Crescent" areas in Asia, China has also become an increasingly important drug consuming market. About half of China's 1.14 million documented drug users inject, and many share needles. IDU has contributed to 42% of cumulatively reported HIV/AIDS cases thus far. Drug trafficking is illegal in China and can lead to the death penalty. The public security departments adopt "zero tolerance" approach to drug use, which conflict with harm reduction policies of the public health departments. Past experience in China suggests that cracking down on drug smuggling and prohibiting drug use alone can not prevent or solve all illicit drug related problems in the era of globalization. In recent years, the central government has outlined a series of pragmatic policies to encourage harm reduction programs; meanwhile, some local governments have not fully mobilized to deal with drug abuse and HIV/AIDS problems seriously. Strengthening government leadership at both central and local levels; scaling up methadone substitution and needle exchange programs; making HIV voluntary counseling and testing available and affordable to both urban and rural drug users; and increasing utilization of outreach and nongovernmental organizations are offered as additional strategies to help cope with China's HIV and drug abuse problem. PMID:16451717

  10. 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.

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

    PubMed Central

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

    2005-01-01

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

  12. 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…

  13. Designing Student Aid Policies for the 1980's.

    ERIC Educational Resources Information Center

    Johnson, Jane Louise

    1980-01-01

    The student financial aid mechanism has been considered the form of subsidy more likely to provide both access and choice since it can target aid to students most in need of it and lets student choose the college of their choice. The Tuition Assistance Program in New York is discussed. (MLW)

  14. 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.

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

    PubMed

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

    2016-01-01

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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Drug design for neglected disease in Brazil.

    PubMed

    Giarolla, Jeanine; Ferreira, Elizabeth Igne

    2015-01-01

    Neglected tropical diseases (NTD) are a group of 17 diseases transmitted by virus, protozoa, helminthes and bacteria. These illnesses are responsible for millions of deaths per year, affecting mainly the poorest populations in the world. The therapeutic drugs available are obsolete, toxic, have questionable efficacy and there are reports of resistance. Therefore, the discovery of new, safe, effective and affordable active molecules is urgently needed. Considering that, the main purpose of this mini-review is to show the current scenario concerning drug design for neglected disease in Brazil. NTD are a very broad topic. Thus, we selected four infections for discussion: Chagas disease, leishmaniasis, malaria and tuberculosis. According to CNPq (National Counsel of Technological and Scientific Development) directories, there are many Brazilian groups studying these respective diseases. The papers published possess high quality and some of them, the most recent, are briefly discussed here. Medicinal chemistry approaches such as synthesis of novel series of molecules and biological activity evaluation, studies of structure-activity relationships (qualitative and quantitative), molecular modeling calculations and electrochemistry are some of the tools applied in the design of the compounds. PMID:25769971

  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. The HIV/AIDS epidemic and changes in injecting drug use in Buenos Aires, Argentina.

    PubMed

    Rossi, Diana; Pawlowicz, María Pía; Rangugni, Victoria; Singh, Dhan Zunino; Goltzman, Paula; Cymerman, Pablo; Vila, Marcelo; Touzé, Graciela

    2006-04-01

    This article discusses the changes in injecting drug use from 1998 to 2003 in Buenos Aires, Argentina. The Rapid Situation Assessment and Response methodology was used to obtain the information. Quantitative and qualitative techniques were triangulated: 140 current IDUs and 35 sex partners of injection drug users (IDUs) were surveyed; 17 in-depth interviews with the surveyed IDUs and 2 focus groups were held, as well as ethnographic observations. The way in which risk and care practices among injecting drug users changed and the influence of the HIV/ AIDS epidemic on this process are described. In recent years, the frequency of injection practices and sharing of injecting equipment has decreased, while injecting drug use is a more hidden practice in a context of increasing impact of the disease in the injecting drug use social networks and changes in the price and quality of drugs. Knowledge about these changes helps build harm reduction activities oriented to IDUs in their particular social context. PMID:16612428

  3. 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

  4. 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...

  5. 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...

  6. 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,...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

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

    Code of Federal Regulations, 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,...

  9. 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...

  10. 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,...

  11. 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,...

  12. 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...

  13. 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,...

  14. 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…

  15. COMPUTER AIDED SOLVENT DESIGN FOR POLLUTION PREVENTION - PARIS II (SYSTEMS ANALYSIS BRANCH, SUSTAINABLE TECHNOLOGY DIVISION, NRMRL)

    EPA Science Inventory

    This method was designed to facilitate the replacement of environmentally objectionable industrial solvents by using computer aided methods to design benign replacement solvents or solvent mixtures. The method generates a short list of recommended replacement solvents or mixtures...

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

    NASA Technical Reports Server (NTRS)

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

    1971-01-01

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

  17. 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

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

    SciTech Connect

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

    1987-01-01

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

  19. Simulation-aided design and synthesis of hierarchically porous membranes.

    PubMed

    Li, Fan; Wilker, Molly B; Stein, Andreas

    2012-05-15

    Free-standing silica membranes with hierarchical porosity (ca. 300 nm macropores surrounded by 6-8 nm mesopores) and controllable mesopore architecture were prepared by a dual-templating method, with the structural design aided by mesoscale simulation. To create a two-dimensional, hexagonal macropore array, polymeric colloidal hemisphere arrays were synthesized by a two-step annealing process starting with non-close-packed polystyrene sphere arrays on silicon coated with a sacrificial alumina layer. A silica precursor containing a poly(ethylene) oxide-poly(propylene oxide)-poly(ethylene) oxide (PEO-PPO-PEO) triblock-copolymer surfactant as template for mesopore creation was spin-coated onto the support and aged and then converted into the free-standing membranes by dissolving both templates and the alumina layer. To test the hypothesis that the mesopore architecture may be influenced by confinement of the surfactant-containing precursor solution in the colloidal array and by its interactions with the polymeric colloids, the system was studied theoretically by dissipative particle dynamics (DPD) simulations and experimentally by examining the pore structures of silica membranes via electron microscopy. The DPD simulations demonstrated that, while only tilted columnar structure can be formed through tuning the interaction with the substrate, perfect alignment of 2D hexagonal micelles perpendicular to the plane of the membrane is achievable by confinement between parallel walls that interact preferentially with the hydrophilic components (PEO blocks, silicate, and solvent). The simulations predicted that this alignment could be maintained across a span of up to 10 columns of micelles, the same length scale defined by the colloidal array. In the actual membranes, we manipulated the mesopore alignment by tuning the solvent polarity relative to the polar surface characteristics of the colloidal hemispheres. With methanol as a solvent, columnar mesopores parallel to the

  20. Structure-based drug design and modern medicine.

    PubMed

    Vijayakrishnan, R

    2009-01-01

    Drug discovery has evolved through various stages into more rational and evidence-based drug designing. Compared to conventional methods which were time consuming and less logical, new drug designing based on structure is rational, evidence based, faster and more scientific in nature. In the era of modern medicine, where newer insights into molecular level of disease processes are available, it is very essential that drug designing be based on molecular mechanism of pathologic processes. Structure-based drug designing has made tremendous contributions in the field of cancer chemotherapy, drug resistant infections, neurological diseases, to mention a few. New drug discovery methods are furthered by developments in the technology especially computers, bioassay techniques and calibrated instruments. Computational structure-based drug designing opens the door to novel treatments in modern medicine. PMID:20083886

  1. 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. PMID:26631222

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

    ERIC Educational Resources Information Center

    Nimphius, Gail M.

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

  3. 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. PMID:25265389

  4. 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.

  5. [Strategy of molecular drug design: hits, leads and drug candidates].

    PubMed

    Guo, Zong-ru

    2008-09-01

    Hits, leads and drug candidates constitute three millstones in the course of drug discovery and development. The definition of drug candidates is a critical point in the value chain of drug innovation, which not only differentiates the research and development stages, but more importantly, determines the perspective and destiny of the pre-clinical and clinical studies. All outcomes from the development stage are actually attributed to the chemical structure of candidates. The quality of candidates, however, is restricted by the drug-likeness of lead compounds, which in turn is decided by the characteristics of hits. The hit-to-lead is to provide a promising and druggable structure for further development, whereas the optimization of lead compounds is a process to transform an active compound into a drug, which in essence is molecular manipulation in multi-dimensional space related to pharmacodynamic, pharmacokinetic, physico-chemical, and safety properties. This review discusses the strategic principles in hit discovery, lead identification and optimization, as well as drug candidate definition with practical examples. PMID:19048779

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

    ERIC Educational Resources Information Center

    Day, Dawn

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

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

    PubMed

    Moretti, Loris; Sartori, Luca

    2016-09-01

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

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

    PubMed Central

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

    2008-01-01

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

  9. A Design for a Model College Financial Aid Office.

    ERIC Educational Resources Information Center

    VanDusen, William D.; O'Hearne, John J.

    Much of the information used in this report on a model college financial aid office prepared for the Coordinating Board, Texas College and University System, was obtained from a survey conducted in 1965-66 by the Bureau of Applied Social Research of Columbia University. As part of the survey, questionnaires were sent to directors of financial aid…

  10. AIDS: caused by development of resistance to drugs in a non-target intracellular parasite.

    PubMed

    Parris, George E

    2007-01-01

    The origin of acquired immune disorder syndrome (AIDS) has been the subject of substantial controversy both in the scientific community and in the popular press. The debate involves the mode of transmission of a simian virus (SIV) to humans. Both major camps in the argument presume that humans are normally free of such viruses and assume that once the simian virus was transmitted, it immediately infected some T-cells and caused the release of toxic agents that killed off bystander (uninfected) T-cells resulting in AIDS. The evolution of the Simian virus (SIV) into a human virus (HIV) is regarded as an artifact. In contrast, a fundamentally different hypothesis has been proposed [Parris GE. Med Hypotheses 2004;62(3):354-7] in which it is presumed that in hyper-endemic areas of malaria (central Africa), all primates (humans and non-human primates) have shared a retrovirus that augments their T-cell response to the malaria parasite. The virus can be called "primate T-cell retrovirus" (PTRV). Over thousands of years the virus has crossed species lines many times (with little effect) and typically adapts to the host quickly. In this model, AIDS is seen to be the result of the development of resistance of the virus (PTRV) to continuous exposure to pro-apoptotic (schizonticidal) aminoquinoline drugs used to prevent malaria. The hypothesis was originally proposed based on biochemical activities of the aminoquinolines (e.g., pamaquine (plasmoquine(TM)), primaquine and chloroquine), but recent publications demonstrated that some of these drugs definitely adversely affect HIV and other viruses and logically would cause them to evolve resistance. Review of the timeline that has been created for the evolution of HIV in humans is also shown to be qualitatively and quantitatively consistent with this hypothesis (and not with either version of the conventional hypothesis). SARS and Ebola also fit this pattern. PMID:16893612

  11. The vehicle design evaluation program - A computer-aided design procedure for transport aircraft

    NASA Technical Reports Server (NTRS)

    Oman, B. H.; Kruse, G. S.; Schrader, O. E.

    1977-01-01

    The vehicle design evaluation program is described. This program is a computer-aided design procedure that provides a vehicle synthesis capability for vehicle sizing, external load analysis, structural analysis, and cost evaluation. The vehicle sizing subprogram provides geometry, weight, and balance data for aircraft using JP, hydrogen, or methane fuels. The structural synthesis subprogram uses a multistation analysis for aerodynamic surfaces and fuselages to develop theoretical weights and geometric dimensions. The parts definition subprogram uses the geometric data from the structural analysis and develops the predicted fabrication dimensions, parts material raw stock buy requirements, and predicted actual weights. The cost analysis subprogram uses detail part data in conjunction with standard hours, realization factors, labor rates, and material data to develop the manufacturing costs. The program is used to evaluate overall design effects on subsonic commercial type aircraft due to parameter variations.

  12. 21 CFR 316.29 - Revocation of orphan-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Revocation of orphan-drug designation. 316.29... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.29 Revocation of orphan-drug designation. (a) FDA may revoke orphan-drug designation for any drug if the agency finds that: (1) The...

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

    ERIC Educational Resources Information Center

    McGrann, Roy T. R.

    2006-01-01

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

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

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

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

  15. 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)

  16. Stigmatization of patients with AIDS: understanding the interrelationships between Thai nurses' attitudes toward HIV/AIDS, drug use, and commercial sex.

    PubMed

    Chan, Kit Yee; Reidpath, Daniel D

    2007-10-01

    There is currently a scarcity of research on the nature of HIV/AIDS stigma within the Thai health context. This is problematic given the negative role of stigma in hindering the provision of patient care and treatment. This study used a mixed-method approach to investigate the interrelationships between the stigma of HIV/AIDS and the stigmas relating to its various modes of disease transmission including injection drug use (IDU). Twenty interviews were conducted with trainees and qualified nurses from a Bangkok college. Participants were presented with vignettes describing a hypothetical person varying in disease diagnoses (AIDS, leukemia, no disease) and co-characteristics (IDU, commercial sex (CS), blood transfusion, no co-characteristic). Using a Q-sort task, participants arranged the vignettes along a bipolar scale according to their willingness to interact with the persons, and were asked to explain their decisions. Univariate and multivariate regression analyses showed that IDU, AIDS, and CS were all individually stigmatizing. Strong interactions were found between the stigmas of HIV/AIDS, IDU, and CS. Interview data also showed clear biases toward patients according to their IDU and CS habits. The findings suggest that addressing these co-stigmas could be vital to the success of efforts aimed at reducing the disease stigma of HIV/AIDS. PMID:17949275

  17. Molecular Rift: Virtual Reality for Drug Designers.

    PubMed

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

    2015-11-23

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

  18. 23 CFR 636.104 - Does this part apply to all Federal-aid design-build projects?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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 2011-04-01 2011-04-01 false Does this part apply to all Federal-aid...

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

    SciTech Connect

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

    2012-02-01

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

  20. 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.

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

    PubMed

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

    2015-02-01

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

  2. 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

  3. Expediting drug development--the FDA's new "breakthrough therapy" designation.

    PubMed

    Sherman, Rachel E; Li, Jun; Shapley, Stephanie; Robb, Melissa; Woodcock, Janet

    2013-11-14

    The FDA's new "breakthrough therapy" designation for investigational drugs adds to the agency's portfolio of expedited programs for serious conditions. The designation requires preliminary clinical evidence demonstrating substantial improvement over existing therapies. PMID:24224621

  4. 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.

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

    PubMed

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

    2015-01-01

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

  6. 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.

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

    PubMed Central

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

    2014-01-01

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

  8. 21 CFR 316.26 - Amendment to orphan-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Amendment to orphan-drug designation. 316.26... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.26 Amendment to orphan-drug designation. (a) At any time prior to approval of a marketing application for a designated orphan drug,...

  9. 21 CFR 316.28 - Publication of orphan-drug designations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Publication of orphan-drug designations. 316.28... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.28 Publication of orphan-drug designations. Each month FDA will update a publically available list of drugs designated as...

  10. 21 CFR 316.25 - Refusal to grant orphan-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Refusal to grant orphan-drug designation. 316.25... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.25 Refusal to grant orphan-drug designation. (a) FDA will refuse to grant a request for orphan-drug designation if any of...

  11. 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.

  12. Anti-HIV drug development: structural features and limitations of present day drugs and future challenges in the successful HIV/AIDS treatment.

    PubMed

    Kumari, Garima; Singh, Ramendra K

    2013-01-01

    Acquired Immune Deficiency Syndrome (AIDS), an immuno-compromized condition, a sequel to untreated human immunodeficiency virus (HIV) infection, inviting several life-threatening diseases, has become one of the most fatal disorders in the recent past because of HIV strain variance due to mutations, passive latency and reservoirs helping in replenishing and reviving the HIV-1 proviral DNA. Scientific efforts have led to the discovery of several effective drugs against HIV and lowered the morbidity and mortality all over the world. However, despite availability of a good number of anti-HIV drugs, the problem, for the foreseeable reasons, stands out as the most chronic disease due to the less tolerability and low accessibility of drugs, life-long expensive treatment, and above all, the emergence of drug resistant viral strains. This review dwells upon HIV infection and its proliferation inside the host system, drug targets, different types of drugs, their structural features and mode of interaction with viral targets and drug regimens. It further focuses on topics of latest interest regarding drug development, fixed dose combinations (FDCs), the limitations of present day drugs with their structural features along with their pharmacodynamics, pharmacokinetics and pharmacogenomics and the challenges in finding a permanent cure for HIV/AIDS. PMID:23092282

  13. 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.

  14. Design and Application of Rolling Circle Amplification for a Tumor-Specific Drug Carrier.

    PubMed

    Kim, Jong Hwan; Jang, Mihue; Kim, Young-Je; Ahn, Hyung Jun

    2015-10-01

    It is challenging to design rolling circle amplification (RCA) for tumor-selective delivery of drugs. Here, we devise a doxorubicin nanocarrier composed of RCA products, cholesterol-DNA, and folate-DNA conjugates. RCA products, designed to contain tandem repeats of short hairpin DNA, employ the repeated sequences complementary to both DNA conjugates, and thus RCA products/cholesterol-DNA/folate-DNA complexes, generated via sequential base pairing processes, acquire the amphiphilic properties that facilitate self-assembly into the highly condensed nanoparticles (RCA nanoparticles). Doxorubicin-loaded RCA nanoparticles, especially with high cargo capacity, release drugs to the environment with the aid of acidity and show selective cytotoxicity to cancer cells. Particularly, the condensed structures enable RCA nanoparticles to be resistant to nucleases in the blood. These results show that RCA nanoparticles have great potential as a doxorubicin carrier for targeted cancer therapy, and furthermore, our strategy provides an alternative tool to exploit RCA techniques on drug delivery systems. PMID:26361253

  15. 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.

  16. CFD Aided Design and Optimization of Francis Turbine Runners

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  17. Association between U.S. State AIDS Drug Assistance Program (ADAP) Features and HIV Antiretroviral Therapy Initiation, 2001–2009

    PubMed Central

    Hanna, David B.; Buchacz, Kate; Gebo, Kelly A.; Hessol, Nancy A.; Horberg, Michael A.; Jacobson, Lisa P.; Kirk, Gregory D.; Kitahata, Mari M.; Korthuis, P. Todd; Moore, Richard D.; Napravnik, Sonia; Patel, Pragna; Silverberg, Michael J.; Sterling, Timothy R.; Willig, James H.; Collier, Ann; Samji, Hasina; Thorne, Jennifer E.; Althoff, Keri N.; Martin, Jeffrey N.; Rodriguez, Benigno; Stuart, Elizabeth A.; Gange, Stephen J.

    2013-01-01

    Background U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes. Methods We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+ <350 cells/uL or AIDS-defining illness) from 14 U.S. cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Using propensity score matching and Cox regression, we assessed ART initiation (within 6 months following eligibility) and virologic suppression (within 1 year) based on differences in two state ADAP features: the amount of state funding in annual ADAP budgets and the implementation of waiting lists. We performed an a priori subgroup analysis in persons with a history of injection drug use (IDU). Results Among 8,874 persons, 56% initiated ART within six months following eligibility. Persons living in states with no additional state contribution to the ADAP budget initiated ART on a less timely basis (hazard ratio [HR] 0.73, 95% CI 0.60–0.88). Living in a state with an ADAP waiting list was not associated with less timely initiation (HR 1.12, 95% CI 0.87–1.45). Neither additional state contributions nor waiting lists were significantly associated with virologic suppression. Persons with an IDU history initiated ART on a less timely basis (HR 0.67, 95% CI 0.47–0.95). Conclusions We found that living in states that did not contribute additionally to the ADAP budget was associated with delayed ART initiation when treatment was clinically indicated. Given the changing healthcare environment, continued assessment of the role of ADAPs and their features that facilitate prompt treatment is needed. PMID:24260137

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

    NASA Astrophysics Data System (ADS)

    Grohn, Matti T.; Nyronen, Tommi N.

    2003-05-01

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

  19. 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. PMID:24974571

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. The B cell mutator AID promotes B lymphoid blast crisis and drug-resistance in chronic myeloid leukemia

    PubMed Central

    Klemm, Lars; Duy, Cihangir; Iacobucci, Ilaria; Kuchen, Stefan; von Levetzow, Gregor; Feldhahn, Niklas; Henke, Nadine; Li, Zhiyu; Hoffmann, Thomas K.; Kim, Yong-mi; Hofmann, Wolf-Karsten; Jumaa, Hassan; Groffen, John; Heisterkamp, Nora; Martinelli, Giovanni; Lieber, Michael R; Casellas, Rafael; Müschen, Markus

    2009-01-01

    Summary Chronic myeloid leukemia (CML) is induced by BCR-ABL1 and can be effectively treated for many years with Imatinib until leukemia cells acquire drug resistance through BCR-ABL1 mutations and progress into fatal B lymphoid blast crisis (LBC). Despite its clinical significance, the mechanism of progression into LBC is unknown. Here we show that LBC but not CML cells express the B cell-specific mutator enzyme AID. We demonstrate that AID expression in CML cells promotes overall genetic instability by hypermutation of tumor suppressor and DNA repair genes. Importantly, our data uncover a causative role of AID activity in the acquisition of BCR-ABL1 mutations leading to Imatinib-resistance, thus providing a rationale for the rapid development of drug resistance and blast crisis progression. PMID:19732723

  5. 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

  6. 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.

  7. Application of fuzzy logic in computer-aided design of digital systems

    NASA Astrophysics Data System (ADS)

    Shragowitz, Eugene B.; Lee, Jun-Yong; Kang, Eric Q.

    1996-06-01

    Application of fuzzy logic structures in computer-aided design (CAD) of electronic systems substantially improves quality of design solutions by providing designers with flexibility in formulating goals and selecting trade-offs. In addition, the following aspects of a design process are positively impacted by application of fuzzy logic: utilization of domain knowledge, interpretation of uncertainties in design data, and adaptation of design algorithms. We successfully applied fuzzy logic structures in conjunction with constructive and iterative algorithms for selecting of design solutions for different stages of the design process. We also introduced a fuzzy logic software development tool to be used in CAD applications.

  8. Computer aided design of a bipolar lead/acid battery

    NASA Astrophysics Data System (ADS)

    Kao, Wen-Hong

    Statistical design of experiments, coupled with the proprietary mathematical lead/acid model of Johnson Controls, Inc., were used to derive the design of a very high power bipolar lead/acid battery for the Jet Propulsion Laboratory. The effects of some battery component factors and discharge rate on the battery performance, predicted by the lead/acid model, were evaluated. The strategy to derive the optimum battery design, the roles of each battery component, limitations of the system, and the directions to improve the battery performance are discussed.

  9. Computer aids for the design of subdivisions for solar access

    SciTech Connect

    Clark, M.M.

    1985-01-01

    Two analytical tools were developed to aid surveyors, architects, and planners in siting solar devices. The tools are in the form of computer programs that produce numerical and graphic data. One program plots the shadows in an area for a given date, time and place. If a composite shadow for an entire day is required, the user can request shadow plots for more than one time. A second program computes the solar envelope for a parcel of land. These are useful for modification of zoning and buildable volume requirements for a parcel. If a dwelling is situated entirely within the envelope, owners of neighboring parcels can be guaranteed that their solar access will be preserved. Output is in the form of elevation differences between the terrain and the envelope and a perspective view of the envelope. Stochastic analysis of the mathematical models is discussed. This includes propagation of random error in the measuring system and comparison of computer generated data with actual ground measurements. Some legal concerns of solar access and the problem of blocking sunlight are also discussed.

  10. Computer-aided designing of automatic process control systems for thermal power stations

    NASA Astrophysics Data System (ADS)

    Trofimov, A. V.

    2009-10-01

    The structure of modern microprocessor systems for automated control of technological processes at cogeneration stations is considered. Methods for computer-aided designing of the lower (sensors and actuators) and upper (cabinets of computerized automation equipment) levels of an automated process control system are proposed. The composition of project documents, the structures of a project database and database of a computer-aided design system, and the way they interact with one another in the course of developing the project of an automated process control system are described. Elements of the interface between a design engineer and computer program are shown.

  11. 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)

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

    SciTech Connect

    Wordin, J.J.

    1990-02-01

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

  13. 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...

  14. Optical design with the aid of a genetic algorithm.

    PubMed

    van Leijenhorst, D C; Lucasius, C B; Thijssen, J M

    1996-01-01

    Natural evolution is widely accepted as being the process underlying the design and optimization of the sensory functions of biological organisms. Using a genetic algorithm, this process is extended to the automatic optimization and design of optical systems, e.g. as used in astronomical telescopes. The results of this feasibility study indicate that various types of aberrations can be corrected quickly and simultaneously, even on small computers. PMID:8924643

  15. 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.

  16. 21 CFR 316.28 - Publication of orphan-drug designations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-drug designations. Each month FDA will update a publically available list of drugs designated as orphan drugs. A cumulative, updated list of all designated drugs will be provided annually. These will be... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Publication of orphan-drug designations....

  17. Optimal experimental design and therapeutic drug monitoring.

    PubMed

    Kulcsár, C; Pronzato, L; Walter, E

    1994-06-01

    A simple example of intravenous theophylline therapy is used to present and compare various drug administration policies based on stochastic control theory. The simplest approach (Heuristic-Certainty-Equivalence (HCE) control) assumes that the model parameters are known. Prior uncertainty on these parameters can be taken into account by using average optimal (AO) control. The available knowledge about the system can be improved by measuring the drug concentration some time after the beginning of the treatment. This corresponds to the notion of feedback and leads to the HCE feedback (HCEF) and AO feedback (AOF) policies. A further step towards optimality consists in choosing the optimal measurement time given that the final purpose is the control of the system and not the estimation of its parameters. Finally, closed-loop optimal (CLO) control optimally chooses both the dosage regimen and measurement time. PMID:7927864

  18. 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.

  19. Computer-aided design of optimal infrared detector preamplifiers

    NASA Astrophysics Data System (ADS)

    Frodsham, D. G.; Baker, D. J.

    1980-01-01

    The paper presents a mathematical model for a frequency-compensated detector-preamplifier suitable for cryogenically cooled IR sensors operating under low background conditions. By the use of a digital computer, this model can rapidly select the optimal combination of design values. These parameters include load resistance, compensation resistance, compensation capacitance, chopping frequency, and detector area to meet desired specifications of noise equivalent power, frequency response, dynamic range, and level of output noise. This computer-assisted optimal design approach is demonstrated using a contemporary spaceborne infrared sensor application, i.e., a cryogenically cooled dual-channel radiometer.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2008-01-01

    Drug discovery is a highly complex and costly process, which demands integrated efforts in several relevant aspects involving innovation, knowledge, information, technologies, expertise, R&D investments and management skills. The shift from traditional to genomics- and proteomics-based drug research has fundamentally transformed key R&D strategies in the pharmaceutical industry addressed to the design of new chemical entities as drug candidates against a variety of biological targets. Therefore, drug discovery has moved toward more rational strategies based on our increasing understanding of the fundamental principles of protein-ligand interactions. The combination of available knowledge of several 3D protein structures with hundreds of thousands of small-molecules have attracted the attention of scientists from all over the world for the application of structure- and ligand-based drug design approaches. In this context, virtual screening technologies have largely enhanced the impact of computational methods applied to chemistry and biology and the goal of applying such methods is to reduce large compound databases and to select a limited number of promising candidates for drug design. This review provides a perspective of the utility of virtual screening in drug design and its integration with other important drug discovery technologies such as high-throughput screening (HTS) and QSAR, highlighting the present challenges, limitations, and future perspectives in medicinal chemistry. PMID:18220761

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

    PubMed

    Spaeth, John P

    2006-02-01

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

  3. Computer-aided design and analysis of mechanisms

    NASA Technical Reports Server (NTRS)

    Knight, F. L.

    1982-01-01

    An introduction to the computer programs developed to assist in the design and analysis of mechanisms is presented. A survey of the various types of programs which are available is given, and the most widely used programs are compared. The way in which the programs are used is discussed, and demonstrated with an example.

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

    ERIC Educational Resources Information Center

    Thompson, M. E.

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

  5. 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

  6. 21 CFR 516.26 - Amendment to MUMS-drug designation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) 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 § 516.26 Amendment to MUMS-drug designation. (a) At...

  7. 21 CFR 516.26 - Amendment to MUMS-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) 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 § 516.26 Amendment to MUMS-drug designation. (a) At...

  8. 21 CFR 516.26 - Amendment to MUMS-drug designation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) 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 § 516.26 Amendment to MUMS-drug designation. (a) At...

  9. Organic Carbamates in Drug Design and Medicinal Chemistry

    PubMed Central

    2016-01-01

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

  10. A common pharmacophoric footprint for AIDS vaccine design.

    PubMed

    Pisterer, Christoph; Mihailescu, Dan; Smith, Jeremy C; Reed, Jennifer

    2004-07-15

    The most promising target antigen for an HIV vaccine designed using the classic antibody strategy has been the viral coat protein gp120. Unfortunately, its high variability has prevented this approach. We examine here a 15-residue peptide derived from the CD4-binding domain of gp120. By use of molecular dynamics computer simulation, it is shown that despite considerable sequence variation, the three-dimensional structure of the peptide is preserved over the full range of clade-specific sequences. Furthermore, sequences threaded onto the structure exhibit common three-dimensional electrostatic and hydrophobic properties. These common physicochemical characteristics constitute a pharmacophoric footprint that promises to be useful in the design of a synthetic antigen for vaccine development. PMID:15239651

  11. The concentration of substance use, criminal justice involvement, and HIV/AIDS in the families of drug offenders.

    PubMed

    Barreras, Ricardo E; Drucker, Ernest M; Rosenthal, David

    2005-03-01

    Substance use (SU), criminal justice involvement (CJI), and HIV/AIDS co-occur in many urban families, but little is known about their intergenerational prevalence and the impact of their conjunction on these families. We determined lifetime prevalence of SU, CJI, and HIV/AIDS in 62 families with a member (the index case) on parole or probation for a drug offense and enrolled in the direct service arm of Family Justice, La Bodega de La Familia--a community support program in New York City's Lower East Side. Among these families, index cases are 94% male, and 97% Latino, with a median age of 37. Records of 80% of open cases, in months March through May, in 2003 (N = 62) were reviewed, and the family maps or "genograms," were analyzed and coded (by age, sex, and relationship to the index) to identify all significant members with histories of SU, CJI, and HIV/AIDS. Of the 62 families (with a total of 592 individuals) 82% had at least one other member besides the index case with a history of SU, 62% had two or more, and 40% had three or more; 72% had one other member with a history of CJI, 45% had two or more, and 24% had three or more. At least one member had HIV/AIDS in 49% of the families, 16% had two or more, and 10% had three or more. Of the 105 family members who reported a history of CJI, 88% had a history of substance use. These data demonstrate the extent to which many families in communities such as this are struggling with the burdens associated with having multiple relatives involved in the criminal justice system, largely related to drug use and frequently with HIV and AIDS. These data point to an important role for family-focused interventions to ameliorate the consequences of high rates of familial drug use, incarceration and other forms of CJI, and HIV/AIDS. PMID:15738327

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

    PubMed

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

    2016-01-01

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

  13. 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

  14. 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

  15. 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. PMID:25459375

  16. 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. PMID:25683749

  17. Modeling the HIV/AIDS epidemic among injecting drug users and sex workers in Kunming, China.

    PubMed

    Bacaër, Nicolas; Abdurahman, Xamxinur; Ye, Jianli

    2006-04-01

    This paper presents a mathematical model of the HIV/AIDS epidemic in Kunming, the provincial capital of Yunnan, China. The population is divided into several groups, with individuals possibly changing group. Two transmission routes of HIV are considered: needle sharing between injecting drug users (IDUs) and commercial sex between female sex worker (FSWs) and clients. The model includes male IDUs who are also clients and female IDUs who are also FSWs. Groups are split in two--risky and safe--according to condom use and needle sharing. A system of partial differential equations is derived to describe the spread of the disease. For the simulation, parameters are chosen to fit as much as possible data publicly available for Kunming. Some mathematical properties of the model--in particular the epidemic threshold R0 which determines the goal of public health interventions--are also presented. Though the model couples two transmission routes of HIV, the approximation R0 approximately = max[R0(IDU), R0(sex)], with closed formulas for R0(IDU) and R0(sex), appears to be quite good. The critical levels of condom use and clean needle use necessary to stop both the sexual transmission and the transmission among IDUs can therefore be determined independently. PMID:16794944

  18. PARP1 Inhibitors: antitumor drug design

    PubMed Central

    Malyuchenko, N. V.; Kotova, E. Yu.; Kulaeva, O. I.; Kirpichnikov, M. P.; Studitskiy, V. M.

    2015-01-01

    The poly (ADP-ribose) polymerase 1 (PARP1) enzyme is one of the promising molecular targets for the discovery of antitumor drugs. PARP1 is a common nuclear protein (1–2 million molecules per cell) serving as a “sensor” for DNA strand breaks. Increased PARP1 expression is sometimes observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. The PARP1 expression level is a prognostic indicator and is associated with a poor survival prognosis. There is evidence that high PARP1 expression and treatment-resistance of tumors are correlated. PARP1 inhibitors are promising antitumor agents, since they act as chemo- and radiosensitizers in the conventional therapy of malignant tumors. Furthermore, PARP1 inhibitors can be used as independent, effective drugs against tumors with broken DNA repair mechanisms. Currently, third-generation PARP1 inhibitors are being developed, many of which are undergoing Phase II clinical trials. In this review, we focus on the properties and features of the PARP1 inhibitors identified in preclinical and clinical trials. We also describe some problems associated with the application of PARP1 inhibitors. The possibility of developing new PARP1 inhibitors aimed at DNA binding and transcriptional activity rather than the catalytic domain of the protein is discussed. PMID:26483957

  19. 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.

  20. Computer aided design of computer generated holograms for electron beam fabrication.

    PubMed

    Urquhart, K S; Lee, S H; Guest, C C; Feldman, M R; Farhoosh, H

    1989-08-15

    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. PMID:20555710

  1. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1983-02-01

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

  3. 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.

  4. 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.

  5. Design and optimization of floating drug delivery system of acyclovir.

    PubMed

    Kharia, A A; Hiremath, S N; Singhai, A K; Omray, L K; Jain, S K

    2010-09-01

    The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992

  6. 21 CFR 316.20 - Content and format of a request for orphan-drug designation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Content and format of a request for orphan-drug designation. 316.20 Section 316.20 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 § 316.20 Content...

  7. 21 CFR 316.28 - Publication of orphan-drug designations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Publication of orphan-drug designations. 316.28 Section 316.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.28 Publication of...

  8. 21 CFR 316.28 - Publication of orphan-drug designations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Publication of orphan-drug designations. 316.28 Section 316.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.28 Publication of...

  9. 21 CFR 316.28 - Publication of orphan-drug designations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Publication of orphan-drug designations. 316.28 Section 316.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.28 Publication of...

  10. 21 CFR 316.30 - Annual reports of holder of orphan-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Annual reports of holder of orphan-drug... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.30 Annual reports of holder of orphan-drug designation. Within 14 months after the date on which a drug was...

  11. Thermo-responsive polymer aided spheroid culture in cryogel based platform for high throughput drug screening.

    PubMed

    Sarkar, J; Kumar, A

    2016-04-21

    In high throughput cell culture, the paradigm is now shifting from 2D to 3D systems. However, in 3D cell culture systems, it is important that the cells form spheroids with robust cell-cell interactions. We fabricated poly(N-isopropylacrylamide-co-gelatin) cryogel scaffolds for cell culture and inserted them into open-ended 96-well plates that formed a drainage and leakage protected, easy to handle high throughput platform. This platform was used to screen for the optimal concentration of poly(N-isopropylacrylamide) (pNIPAAm) as an external aid to the formation of cellular spheroids. It was found that hepatic cells (Hep G2) seeded in the presence of 0.03% pNIPAAm formed better hepatic spheroids in terms of morphology (as assessed by microscopic analysis and formation of bile canaliculi-like structures) and functionality by day 5 of culture. An increase of 44.22%, 15.75%, 36.44%, 32.05% and 27.02% was observed in glucose consumption (1.925 mM per day per 10(4) cells), albumin synthesis (164.18 ng per day per 10(4) cells), CYP1A1 (304.92 pg per min per 10(4) cells), CYP2A6 (441.23 nM per min per 10(4) cells) and phase II metabolic activity (386.18 nM per min(-1) per 10(4) cells), respectively, upon using 0.03% pNIPAAm, as compared to the 3D control. The platform was tested with other cells such as breast and lung cancer cells and found to be compatible. The cell spheroids were subjected to drug toxicity screening in cryogel based open-ended platforms. It was observed that the spheroids were more resistant to anticancer drugs, as compared to 2D and 3D controls, with approximately 11%-67% increase in the IC50 values of tamoxifen and paclitaxel. The platform also showed dose dependent and reproducible responses to drugs. PMID:27027476

  12. 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.

  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. Drug-eluting stents: role of stent design, delivery vehicle, and drug selection.

    PubMed

    Rodgers, Campbell D K

    2002-01-01

    Increasing focus has recently been directed toward the different parameters of drug-eluting stents-stent design, delivery-vehicle materials, and drug properties-and the manner in which each of these elements may affect the function of the stents. Several specific characteristics of design may affect restenosis, although design optimization often presents a choice between acute procedural success and long-term biological stability. The influence of design parameters such as strut thickness and cell configuration is described. Polymer material has frequently been used to coat drug-eluting stents, although some agents, such as paclitaxel, can be attached directly to the stent's surface, obviating the need for a polymer layer. The properties of agents used in drug-eluting stents and how those properties affect delivery and long-term outcome are discussed, as is the influence of the disease state of the target vessel on stent safety and efficacy. PMID:12478230

  15. 21 CFR 516.23 - Timing of requests for MUMS-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.23 Timing of requests for MUMS-drug designation. A sponsor may request MUMS-drug designation at any time in the drug...

  16. 21 CFR 516.23 - Timing of requests for MUMS-drug designation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.23 Timing of requests for MUMS-drug designation. A sponsor may request MUMS-drug designation at any time in the drug...

  17. 21 CFR 516.23 - Timing of requests for MUMS-drug designation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.23 Timing of requests for MUMS-drug designation. A sponsor may request MUMS-drug designation at any time in the drug...

  18. 21 CFR 316.27 - Change in ownership of orphan-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  19. 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.

  20. Application of SMILES Notation Based Optimal Descriptors in Drug Discovery and Design.

    PubMed

    Veselinović, Aleksandar M; Veselinović, Jovana B; Živković, Jelena V; Nikolić, Goran M

    2015-01-01

    SMILES notation based optimal descriptors as a universal tool for the QSAR analysis with further application in drug discovery and design is presented. The basis of this QSAR modeling is Monte Carlo method which has important advantages over other methods, like the possibility of analysis of a QSAR as a random event, is discussed. The advantages of SMILES notation based optimal descriptors in comparison to commonly used descriptors are defined. The published results of QSAR modeling with SMILES notation based optimal descriptors applied for various pharmacologically important endpoints are listed. The presented QSAR modeling approach obeys OECD principles and has mechanistic interpretation with possibility to identify molecular fragments that contribute in positive and negative way to studied biological activity, what is of big importance in computer aided drug design of new compounds with desired activity. PMID:25961525

  1. 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.

  2. Wireless Hearing Aid System Simulations using Advanced Design System™: A Behavioral Modeling Approach.

    PubMed

    Singh Rana, Ram; Bin, Tang; Liang, Zhang; Hari Krishna, Garg; De Yun, Wang

    2005-01-01

    The stringent requirements on size and power consumption constrain the conventional hearing aid devices from providing the patients an economic and user friendly solution, specifically for better noise cancellation. With the advancements in technologies such as integrated circuits design, wireless communications and digital signal processing techniques, the wireless hearing aids having multi-microphones, analog, digital and mixed signals and radio frequency signals processing circuits, DSP and programmable units seem to be promising to provide enhanced performance. The focus of this paper is about the system simulation of a typical wireless hearing aid using Agilent Advanced Design System™. The behavioral modeling features are exploited to enable the whole system simulations including electro-acoustic transducers. A few system level simulation results are included. PMID:17282359

  3. 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

  4. Design of a multiple drug delivery system directed at periodontitis.

    PubMed

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

    2013-11-01

    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

  5. 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.

  6. [Computer-aided design of polyketides with the required properties].

    PubMed

    Sergeĭko, A P; Stepanchikova, A V; Sobolev, B N; Zotchev, S B; Lagunin, A A; Filimonov, D A; Poroĭkov, V V

    2007-01-01

    We propose an approach to rational design of new polyketides with the required spectrum of biological activity. We developed BioGenPharm software for generation of polyketide combinatorial libraries, prediction of activity spectra for the generated structures and selection of molecules with the required properties on the basis of user defined input parameters and selection criteria. For prediction of polyketide activity spectra we used PASS algorithm (http://www.ibmc.msk.ru/PASS). Validation of PASS prediction ability for polyketides was performed vs. the evaluation set containing 242 natural macrolides from the Dictionary of Natural Products. The mean prediction accuracy was 75,5%. The problem of choice of cutting points for probability of the presence of activity (Pa), which provide optimal combination of such parameters as sensitivity, specificity, concordance was considered. Applicability of the described method has been illustrated by generation of a virtual library of the erythromycin analogues and selection substances for which the probability of hepatotoxic action is low. PMID:18078066

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

    PubMed

    Caposecco, Andrea; Hickson, Louise; Meyer, Carly

    2011-12-01

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

  8. 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.

  9. Design of an implantable device for ocular drug delivery.

    PubMed

    Lee, Jae-Hwan; Pidaparti, Ramana M; Atkinson, Gary M; Moorthy, Ramana S

    2012-01-01

    Ocular diseases, such as, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa require drug management in order to prevent blindness and affecting million of adults in USA and worldwide. There is an increasing need to develop devices for drug delivery to address ocular diseases. This study focuses on the design, simulation, and development of an implantable ocular drug delivery device consisting of micro-/nanochannels embedded between top and bottom covers with a drug reservoir made from polydimethylsiloxane (PDMS) which is silicon-based organic and biodegradable polymer. Several simulations were carried out with six different micro-channel configurations in order to see the feasibility for ocular drug delivery applications. Based on the results obtained, channel design of osmotic I and osmotic II satisfied the diffusion rates required for ocular drug delivery. Finally, a prototype illustrating the three components of the drug delivery design is presented. In the future, the device will be tested for its functionality and diffusion characteristics. PMID:22919500

  10. 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.

  11. 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

  12. Designer drugs: pipe-dreams or realities?

    PubMed

    Gutteridge, W E

    1997-01-01

    New chemotherapies are urgently needed for the parasitic infections of animals and for the tropical diseases of man. Rational molecular design approaches to attempt to discover such products require a massive investment of resources upfront of actual chemical synthesis. However, such investment is justified, since chemical synthesis itself is highly resource-consuming. The fact that few targets have yet been validated to justify a rational approach is an argument only to get on and validate more. Not all the components of molecular design can yet be done totally rationally, but this is not an argument against applying this approach where it is possible. Absence of a successful track record is inevitable for any newly emerging technology. It is too early to draw conclusions about the relative costs of rational design versus empirical synthesis, since the former is only now beginning to become reality and the latter is in the middle of a (combinatorial) revolution. Similarly, it is too soon to predict with certainty which of these two approaches will prevail in the long run. However, they lend themselves to parallel tracks, so both may well continue for the foreseeable future. Current concerns about who would develop successful discoveries are not reasons for stopping discovery research. Indeed, a string of putative products held at the discovery/development interface would be useful ammunition to those trying to develop partnerships such as a Tropical Diseases R & D Alliance aimed at carrying out such work and sharing costs. PMID:9309776

  13. 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

  14. 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

  15. 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

  16. De Novo Fragment Design for Drug Discovery and Chemical Biology.

    PubMed

    Rodrigues, Tiago; Reker, Daniel; Welin, Martin; Caldera, Michael; Brunner, Cyrill; Gabernet, Gisela; Schneider, Petra; Walse, Björn; Schneider, Gisbert

    2015-12-01

    Automated molecular de novo design led to the discovery of an innovative inhibitor of death-associated protein kinase 3 (DAPK3). An unprecedented crystal structure of the inactive DAPK3 homodimer shows the fragment-like hit bound to the ATP pocket. Target prediction software based on machine learning models correctly identified additional macromolecular targets of the computationally designed compound and the structurally related marketed drug azosemide. The study validates computational de novo design as a prime method for generating chemical probes and starting points for drug discovery. PMID:26486226

  17. 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…

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

    SciTech Connect

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

    1988-07-11

    This report provides an overview of the state of the art of personal computer (PC)-based computer-aided design and drafting (CADD) systems for mechanical engineering applications. It presents the results of an evaluation performed on seven systems during October 1987 to March 1988 and summarizes the strengths and weaknesses of the systems.

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

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    The purpose and direction of the Office of Student Financial Aid (OSFA) quality improvement program are described. The background and context for the Pell Grant quality control (QC) design study and the meaning of QC are reviewed. The general approach to quality improvement consists of the following elements: a strategic approach that enables OSFA…

  20. 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…

  1. 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…

  2. Improving a Student's Reading Comprehension Skills by Teaching Computer Aided Design.

    ERIC Educational Resources Information Center

    Bentivolio, Kerry

    A serendipitous observation resulted in an examination of the effectiveness of using a computer aided design course to improve high school student's strategic reading skills. Conducted in a 3 month semester period, the study relied on teacher observations, student questionnaires, and personal interviews. More than 75% of the students in the…

  3. 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…

  4. 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…

  5. New Spaces for Learning: Designing College Facilities to Utilize Instructional Aids and Media. Revised.

    ERIC Educational Resources Information Center

    Hauf, Harold D.; And Others

    Colleges need appropriate large group instructional facilities for effective and efficient use of instructional aids and media. A well planned system of facilities must provide space for learning; production, origination, and support; storage and retrieval. Design begins with a building plan--a statement, made jointly by the administrator and…

  6. 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…

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

    PubMed

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

    2016-01-01

    Decision support systems for alert drug-drug interactions have been shown as valid strategy to reduce medical error. Even so the use of these systems has not been as expected, probably due to the lack of a suitable design. This study compares two interfaces, one of them developed using participatory design techniques (based on user centered design processes). This work showed that the use of these techniques improves satisfaction, effectiveness and efficiency in an alert system for drug-drug interactions, a fact that was evident in specific situations such as the decrease of errors to meet the specified task, the time, the workload optimization and users overall satisfaction with the system. PMID:27577343

  8. 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. PMID:22317485

  9. 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

  10. Modeling And Simulation Of Bar Code Scanners Using Computer Aided Design Software

    NASA Astrophysics Data System (ADS)

    Hellekson, Ron; Campbell, Scott

    1988-06-01

    Many optical systems have demanding requirements to package the system in a small 3 dimensional space. The use of computer graphic tools can be a tremendous aid to the designer in analyzing the optical problems created by smaller and less costly systems. The Spectra Physics grocery store bar code scanner employs an especially complex 3 dimensional scan pattern to read bar code labels. By using a specially written program which interfaces with a computer aided design system, we have simulated many of the functions of this complex optical system. In this paper we will illustrate how a recent version of the scanner has been designed. We will discuss the use of computer graphics in the design process including interactive tweaking of the scan pattern, analysis of collected light, analysis of the scan pattern density, and analysis of the manufacturing tolerances used to build the scanner.

  11. Integration of computer-aided design and manufacturing through artificial-intelligence-based process planning

    SciTech Connect

    Arunthavanathan, V.

    1988-01-01

    The research effort reported in this thesis is directed towards the integration of design, process planning, and manufacturing. The principal notion used in system integration through information integration. The main outcome of this research effort is an artificial-intelligence-based computer-aided generative process planning system, which would use a feature-based symbolic geometry as its input. The feature-based symbolic data structure is used as the common data between design, process planning, and manufacturing. As the commercial computer-aided design systems would not generate a feature-based data base, special interfaces are designed and used. As part of the solution strategy, a module to analyze the symbolic geometry from a global perspective is developed. This module imitates a human process planner and derives some overall assertions. The enhanced geometry data is then used by a rule-based expert system to develop the process plan.

  12. 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.

  13. 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.

  14. Design and implementation of an electronic investigational drug accountability system.

    PubMed

    Grilley, B J; Trissel, L A; Bluml, B M

    1991-12-01

    A software system designed to maintain protocol-specific investigational drug accountability records is described. The University of Texas M. D. Anderson Cancer Center and Cygnus Systems Development, Inc., worked together to create an electronic investigational drug accountability system (IDRx), which meets the requirements of the National Cancer Institute. This system performs record keeping, stores information on drugs and protocols, and generates standard and customized reports. On-screen assistance makes it easy to use. Security is achieved by granting access only to authorized users, and an audit trail is automatically generated. Systematic implementation at M. D. Anderson, initially in the investigational drug control area and subsequently in the satellite pharmacies, has resulted in increased accuracy and efficiency, and few problems have been encountered. The IDRx software package is useful for keeping records, generating reports, and tracking and evaluating data associated with an investigational drug accountability system. PMID:1814202

  15. 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

  16. Advancing lighting and daylighting simulation: The transition from analysis to design aid tools

    SciTech Connect

    Hitchcock, R.J.

    1995-05-01

    This paper explores three significant software development requirements for making the transition from stand-alone lighting simulation/analysis tools to simulation-based design aid tools. These requirements include specialized lighting simulation engines, facilitated methods for creating detailed simulatable building descriptions, an automated techniques for providing lighting design guidance. Initial computer implementations meant to address each of these requirements are discussed to further elaborate these requirements and to illustrate work-in-progress.

  17. 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.

  18. 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. PMID:26059362

  19. Computational drug design targeting protein-protein interactions.

    PubMed

    Bienstock, Rachelle J

    2012-01-01

    Novel discoveries in molecular disease pathways within the cell, combined with increasing information regarding protein binding partners has lead to a new approach in drug discovery. There is interest in designing drugs to modulate protein-protein interactions as opposed to solely targeting the catalytic active site within a single enzyme or protein. There are many challenges in this new approach to drug discovery, particularly since the protein-protein interface has a larger surface area, can comprise a discontinuous epitope, and is more amorphous and less well defined than the typical drug design target, a small contained enzyme-binding pocket. Computational methods to predict modes of protein-protein interaction, as well as protein interface hot spots, have garnered significant interest, in order to facilitate the development of drugs to successfully disrupt and inhibit protein-protein interactions. This review summarizes some current methods available for computational protein-protein docking, as well as tabulating some examples of the successful design of antagonists and small molecule inhibitors for protein-protein interactions. Several of these drugs are now beginning to appear in the clinic. PMID:22316151

  20. Viral proteases as targets for drug design.

    PubMed

    Skoreński, Marcin; Sieńczyk, Marcin

    2013-01-01

    In order to productively infect a host, viruses must enter the cell and force host cell replication mechanisms to produce new infectious virus particles. The success of this process unfortunately results in disease progression and, in the case of infection with many viral species, may cause mortality. The discoveries of Louis Pasteur and Edward Jenner led to one of the greatest advances in modern medicine - the development of vaccines that generate long-lasting memory immune responses to combat viral infection. Widespread use of vaccines has reduced mortality and morbidity associated with viral infection and, in some cases, has completely eradicated virus from the human population. Unfortunately, several viral species maintain a significant ability to mutate and "escape" vaccine-induced immune responses. Thus, novel anti-viral agents are required for treatment and prevention of viral disease. Targeting proteases that are crucial in the viral life cycle has proven to be an effective method to control viral infection, and this avenue of investigation continues to generate anti-viral treatments. Herein, we provide the reader with a brief history as well as a comprehensive review of the most recent advances in the design and synthesis of viral protease inhibitors. PMID:23016690

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Content and format of a request for orphan-drug... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.20 Content and format of a request for orphan-drug designation. (a) A sponsor that submits a request for...

  2. From addiction to infection: managing drug abuse in the context of HIV/AIDS in Africa.

    PubMed

    Akindipe, Taiwo; Abiodun, Lolade; Adebajo, Sylvia; Lawal, Rahman; Rataemane, Solomon

    2014-09-01

    People who use drugs are at higher risk of HIV: directly through the sharing of injecting equipment, indirectly through associated risk behavior, and physiologically through the substances' impact on the immune system. Drug users, especially people who inject drugs (PWID) are a bridge to the general population. The treatment of drug addiction and provision of harm reduction interventions have impact on HIV transmission and incidence. Addiction treatment reduces the frequency of drug-related risky behaviors and enhances access and adherence to HIV treatment, resulting in fewer new infections. However, the drug policies of many African countries are punitive and hostile to harm reduction programs. These fuel criminalization of drug use and discrimination against the drug user thereby preventing individuals with drug addiction from accessing treatment programs. There is need to formulate policies aimed at protecting the rights of people with drug addiction and address the ethical aspects of treatment. PMID:26050376

  3. 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

  4. A Successful Model and Visual Design for Creating Context-Aware Drug-Drug Interaction Alerts

    PubMed Central

    Duke, Jon D.; Bolchini, Davide

    2011-01-01

    Evaluating the potential harm of a drug-drug interaction (DDI) requires knowledge of a patient’s relevant co-morbidities and risk factors. Current DDI alerts lack such patient-specific contextual data. In this paper, we present an efficient model for integrating pertinent patient data into DDI alerts. This framework is designed to be interoperable across multiple drug knowledge bases and clinical information systems. To evaluate the model, we generated a set of contextual DDI data using our local drug knowledge base then conducted an evaluation study of a prototype contextual alert design. The alert received favorable ratings from study subjects, who agreed it was an improvement over traditional alerts and was likely to support clinical management and save physician time. This framework may ultimately help reduce alert fatigue through the dynamic display of DDI alerts based on patient risk. PMID:22195086

  5. Enhancements to the Design Manager's Aide for Intelligent Decomposition (DeMaid)

    NASA Technical Reports Server (NTRS)

    Rogers, James L.; Barthelemy, Jean-Francois M.

    1992-01-01

    This paper discusses the addition of two new enhancements to the program Design Manager's Aide for Intelligent Decomposition (DeMAID). DeMAID is a knowledge-based tool used to aid a design manager in understanding the interactions among the tasks of a complex design problem. This is done by ordering the tasks to minimize feedback, determining the participating subsystems, and displaying them in an easily understood format. The two new enhancements include (1) rules for ordering a complex assembly process and (2) rules for determining which analysis tasks must be re-executed to compute the output of one task based on a change in input to that or another task.

  6. Enhancements to the Design Manager's Aide for Intelligent Decomposition (DeMAID)

    NASA Technical Reports Server (NTRS)

    Rogers, James L.; Barthelemy, Jean-Francois M.

    1992-01-01

    This paper discusses the addition of two new enhancements to the program Design Manager's Aide for Intelligent Decomposition (DeMAID). DeMAID is a knowledge-based tool used to aid a design manager in understanding the interactions among the tasks of a complex design problem. This is done by ordering the tasks to minimize feedback, determining the participating subsystems, and displaying them in an easily understood format. The two new enhancements include (1) rules for ordering a complex assembly process and (2) rules for determining which analysis tasks must be re-executed to compute the output of one task based on a change in input to that or another task.

  7. 21 CFR 316.40 - Treatment use of a designated orphan drug.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Treatment use of a designated orphan drug. 316.40... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Open Protocols for Investigations § 316.40 Treatment use of a designated orphan drug. Prospective investigators seeking to obtain treatment use of designated orphan...

  8. Nanobiological studies on drug design using molecular mechanic method

    PubMed Central

    Ghaheh, Hooria Seyedhosseini; Mousavi, Maryam; Araghi, Mahmood; Rasoolzadeh, Reza; Hosseini, Zahra

    2015-01-01

    Background: Influenza H1N1 is very important worldwide and point mutations that occur in the virus gene are a threat for the World Health Organization (WHO) and druggists, since they could make this virus resistant to the existing antibiotics. Influenza epidemics cause severe respiratory illness in 30 to 50 million people and kill 250,000 to 500,000 people worldwide every year. Nowadays, drug design is not done through trial and error because of its cost and waste of time; therefore bioinformatics studies is essential for designing drugs. Materials and Methods: This paper, infolds a study on binding site of Neuraminidase (NA) enzyme, (that is very important in drug design) in 310K temperature and different dielectrics, for the best drug design. Information of NA enzyme was extracted from Protein Data Bank (PDB) and National Center for Biotechnology Information (NCBI) websites. The new sequences of N1 were downloaded from the NCBI influenza virus sequence database. Drug binding sites were assimilated and homologized modeling using Argus lab 4.0, HyperChem 6.0 and Chem. D3 softwares. Their stability was assessed in different dielectrics and temperatures. Result: Measurements of potential energy (Kcal/mol) of binding sites of NA in different dielectrics and 310K temperature revealed that at time step size = 0 pSec drug binding sites have maximum energy level and at time step size = 100 pSec have maximum stability and minimum energy. Conclusions: Drug binding sites are more dependent on dielectric constants rather than on temperature and the optimum dielectric constant is 39/78. PMID:26605248

  9. [Design of the novel dipeptide neuropsychotropic drug preparations].

    PubMed

    Gudasheva, T A; Skoldinov, A P

    2003-01-01

    The paper considers a new strategy in the field of neuropsychotropic dipeptide drug design, the main points being as follows: (i) determination of the structural elements of dipeptides, such as fragments of amino acid side radicals and peptide bonds, in nonpeptide drugs; (ii) design of peptide analogs topologically close to the drug; (iii) synthesis and activity testing of these analogs; (iv) determination of the corresponding endogenous neuropeptide among the known neuropeptides or identification of the new neuropeptides in the brain of experimental animals. Using this approach, new pyroglutamyl- and prolyl-containing dipeptides were obtained based on the structure of the well-known classical nootropic drug piracetam. The new drugs exhibit nootropic activity in doses 100-10,000 times lower than those of piracetam. The structure of most active pyroglutamyl dipeptide pGlu-Asn-NH2 coincides with that of the N-end fragment of the endogenous memory peptide AVP(4-9). Noopept (N-phenylacetylprolylglycine ethyl ester), patented in Russia and USA as a new nootropic drug, is currently under stage 2 of successful clinical trials. The main metabolite of noopept, cyclo-Pro-Gly, is identical to the endogenous dipeptide designed in this work and is most close analog of piracetam with respect to pharmacological activity. The universal character of the proposed strategy is demonstrated by the design of active dipeptide analogs of an atypical neuroleptic drug sulpiride. As a result, a potential dipeptide neuroleptic dilept was obtained, which has been patented in Russia and now passes broad preclinical trials. PMID:12962042

  10. Designing drug regimens for special intensive care unit populations

    PubMed Central

    Erstad, Brian L

    2015-01-01

    This review is intended to help clinicians design drug regimens for special populations of critically ill patients with extremes of body size, habitus and composition that make drug choice or dosing particularly challenging due to the lack of high-level evidence on which to make well-informed clinical decisions. The data sources included a literature search of MEDLINE and EMBASE with reviews of reference lists of retrieved articles. Abstracts of original research investigations and review papers were reviewed for their relevance to drug choice or dosing in the following special critically ill populations: patients with more severe forms of bodyweight or height, patients with amputations or missing limbs, pregnant patients, and patients undergoing extracorporeal membrane oxygenation or plasma exchange. Relevant papers were retrieved and evaluated, and their associated reference lists were reviewed for citations that may have been missed through the electronic search strategy. Relevant original research investigations and review papers that could be used to formulate general principles for drug choice or dosing in special populations of critically ill patients were extracted. Randomized studies with clinically relevant endpoints were not available for performing quantitative analyses. Critically ill patients with changes in body size, habitus and composition require special consideration when designing medication regimens, but there is a paucity of literature on which to make drug-specific, high-level evidence-based recommendations. Based on the evidence that is available, general recommendations are provided for drug choice or dosing in special critically ill populations. PMID:25938029

  11. Design Features of Drug-Drug Interaction Trials Between Antivirals and Oral Contraceptives.

    PubMed

    Ayala, Ruben C; Arya, Vikram; Younis, Islam R

    2016-05-01

    The aim of this work was to explore the major design features of drug-drug interaction trials between antiviral medications (AVs) and oral contraceptives (OCs). Information on these trials (n = 27) was collected from approved drug labels and clinical pharmacology reviews conducted by the U.S. Food and Drug Administration. The primary objective of all trials was to evaluate changes in OC exposure following the coadministration of AVs. In addition, an evaluation of potential pharmacodynamic interaction was performed in 10 of these trials. Twenty-two trials were open label with a fixed-sequence design, and 5 trials used a double-blind crossover design. The trials were conducted using one, two, or three 28-day ovulatory cycles in 10, 8, and 9 trials, respectively. Only 1 trial enrolled HIV-infected women. The median number of women in a trial was 20 (range, 12 to 52). Norethindrone/ethinyl estradiol (EE) combination was the most commonly used OC (n = 16, 59%) followed by norgestimate/EE (n = 9, 33%). Labeling recommendations were based on exposure changes in 25 cases and on safety observations in the trial in 2 cases. In conclusion, a wide variety of trial designs was used, and there is no preferred design. The answer to the exposure question can be achieved using multiple designs. PMID:26384089

  12. Design of Microbubbles for Gene/Drug Delivery.

    PubMed

    Bettinger, Thierry; Tranquart, François

    2016-01-01

    The role of ultrasound contrast agents (UCA) initially designed for diagnosis has evolved towards a therapeutic use. Ultrasound (US) for triggered drug delivery has many advantages. In particular, it enables a high spatial control of drug release, thus potentially allowing activation of drug delivery only in the targeted region, and not in surrounding healthy tissue. Moreover, UCA imaging can also be used firstly to precisely locate the target region to, and then used to monitor the drug delivery process by tracking the location of release occurrence. All these features make UCA and ultrasound attractive means to mediate drug delivery. The three main potential clinical indications for drug/gene US delivery are (i) the cardiovascular system, (ii) the central nervous system for small molecule delivery, and (iii) tumor therapy using cytotoxic drugs. Although promising results have been achieved in preclinical studies in various animal models, still very few examples of clinical use have been reported. In this chapter will be addressed the aspects pertaining to UCA formulation (chemical composition, mode of preparation, analytical methods…) and the requirement for a potential translation into the clinic following approval by regulatory authorities. PMID:26486339

  13. 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.

  14. Learning to design resistance proof drugs from folding

    NASA Astrophysics Data System (ADS)

    Broglia, R. A.

    2009-01-01

    Learning how proteins fold will hardly have any impact on the way conventional — active site centered — drugs are designed. On the other hand, this knowledge is proving instrumental in defining a new paradigm for the identification of drugs against any target protein: folding inhibition. Targeting folding renders drugs less susceptible to spontaneous genetic mutations that in many cases, notably in connection with retroviruses like the Human Immunodeficiency Virus (HIV), can abrogate drug effect. The progress which has taken place during the last years to understand which are the sequences of amino acids which code for a protein, and how to read from these sequences the associated three-dimensional, biologically active, native structure, constitutes the main subject of the present paper. From this narrative the idea of folding inhibitors emerges both naturally and, to some extent, inescapably.

  15. Computer-aided optimization of grid design for high-power lead-acid batteries

    NASA Astrophysics Data System (ADS)

    Yamada, Keizo; Maeda, Ken-ichi; Sasaki, Kazuya; Hirasawa, Tokiyoshi

    Several high-power lead-acid batteries have been developed for automotive applications. A computer-aided optimization (CAO) technique has been used to obtain a low-resistance grid design. Unlike conventional computer simulation, the CAO technique does not require an unduly large number of designs to yield a good result. After introducing a pair of differential equations that are expected to be valid for the optimized design, the grid thickness is optimized by solving the boundary value problem of coupled differential equations. When applied for the grids of JIS B-size batteries, this technique reduces the potential drop of electrical resistance in a electrode by 11-14%.

  16. Computer-Aided Designed, 3-Dimensionally Printed Porous Tissue Bioscaffolds For Craniofacial Soft Tissue Reconstruction

    PubMed Central

    Zopf, David A.; Mitsak, Anna G.; Flanagan, Colleen L.; Wheeler, Matthew; Green, Glenn E.; Hollister, Scott J.

    2016-01-01

    Objectives To determine the potential of integrated image-based Computer Aided Design (CAD) and 3D printing approach to engineer scaffolds for head and neck cartilaginous reconstruction for auricular and nasal reconstruction. Study Design Proof of concept revealing novel methods for bioscaffold production with in vitro and in vivo animal data. Setting Multidisciplinary effort encompassing two academic institutions. Subjects and Methods DICOM CT images are segmented and utilized in image-based computer aided design to create porous, anatomic structures. Bioresorbable, polycaprolactone scaffolds with spherical and random porous architecture are produced using a laser-based 3D printing process. Subcutaneous in vivo implantation of auricular and nasal scaffolds was performed in a porcine model. Auricular scaffolds were seeded with chondrogenic growth factors in a hyaluronic acid/collagen hydrogel and cultured in vitro over 2 months duration. Results Auricular and nasal constructs with several microporous architectures were rapidly manufactured with high fidelity to human patient anatomy. Subcutaneous in vivo implantation of auricular and nasal scaffolds resulted in excellent appearance and complete soft tissue ingrowth. Histologic analysis of in vitro scaffolds demonstrated native appearing cartilaginous growth respecting the boundaries of the scaffold. Conclusions Integrated image-based computer-aided design (CAD) and 3D printing processes generated patient-specific nasal and auricular scaffolds that supported cartilage regeneration. PMID:25281749

  17. 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.

  18. The significance of chirality in drug design and development.

    PubMed

    Brooks, W H; Guida, W C; Daniel, K G

    2011-01-01

    Proteins are often enantioselective towards their binding partners. When designing small molecules to interact with these targets, one should consider stereoselectivity. As considerations for exploring structure space evolve, chirality is increasingly important. Binding affinity for a chiral drug can differ for diastereomers and between enantiomers. For the virtual screening and computational design stage of drug development, this problem can be compounded by incomplete stereochemical information in structure libraries leading to a "coin toss" as to whether or not the "ideal" chiral structure is present. Creating every stereoisomer for each chiral compound in a structure library leads to an exponential increase in the number of structures resulting in potentially unmanageable file sizes and screening times. Therefore, only key chiral structures, enantiomeric pairs based on relative stereochemistry need be included, and lead to a compromise between exploration of chemical space and maintaining manageable libraries. In clinical environments, enantiomers of chiral drugs can have reduced, no, or even deleterious effects. This underscores the need to avoid mixtures of compounds and focus on chiral synthesis. Governmental regulations emphasizing the need to monitor chirality in drug development have increased. The United States Food and Drug Administration issued guidelines and policies in 1992 concerning the development of chiral compounds. These guidelines require that absolute stereochemistry be known for compounds with chiral centers and that this information should be established early in drug development in order that the analysis can be considered valid. From exploration of structure space to governmental regulations it is clear that the question of chirality in drug design is of vital importance. PMID:21291399

  19. 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.…

  20. 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)…

  1. 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.

  2. 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.

  3. Computer-Aided Design/Manufacturing (CAD/M) for high-speed interconnect

    NASA Astrophysics Data System (ADS)

    Santoski, N. F.

    1981-10-01

    The objective of the Computer-Aided Design/Manufacturing (CAD/M) for High-Speed Interconnect Program study was to assess techniques for design, analysis and fabrication of interconnect structures between high-speed logic ICs that are clocked in the 200 MHz to 5 GHz range. Interconnect structure models were investigated and integrated with existing device models. Design rules for interconnects were developed in terms of parameters that can be installed in software that is used for the design, analysis and fabrication of circuits. To implement these design rules in future software development, algorithms and software development techniques were defined. Major emphasis was on Printed Wiring Board and hybrid level circuits as opposed to monolithic chips. Various packaging schemes were considered, including controlled impedance lines in the 50 to 200 ohms range where needed. The design rules developed are generic in nature, in that various architecture classes and device technologies were considered.

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

    PubMed

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

    2015-12-01

    Recently, the abuse of designer drugs has become a social problem. Designer drugs are created by modifying part of the chemical structure of drugs that have already been categorized as illegal, thereby creating a different chemical compound in order to evade Pharmaceutical Affairs Law regulations. The new comprehensive system for designating illegal drug components has been in effect since March 2013, and many designer drugs can now be regulated. We conducted an online questionnaire survey of people with a history of designer drug use to elucidate the effects of the new system on the abuse of designer drugs and to identify potential future problems. Over half the subjects obtained designer drugs only before the new system was implemented. Awareness of the system was significantly lower among subjects who obtained designer drugs for the first time after its introduction than those who obtained the drugs only before its implementation. Due to the new system, all methods of acquiring designer drugs saw decreases in activity. However, the ratio of the acquisition of designer drugs via the Internet increased. Since over 50% of the subjects never obtained designer drugs after the new system was introduced, goals that aimed to make drug procurement more difficult were achieved. However, awareness of the new system among subjects who obtained designer drugs after the new system was introduced was significantly low. Therefore, fostering greater public awareness of the new system is necessary. The results of the questionnaire also suggested that acquiring designer drugs through the Internet has hardly been affected by the new system. We strongly hope that there will be a greater push to restrict the sale of designer drugs on the Internet in the near future. PMID:26975077

  5. Mandibular Reconstruction Using a Custom-Made Titanium Prosthesis: A Case Report on the Use of Virtual Surgical Planning and Computer-Aided Design/Computer-Aided Manufacturing.

    PubMed

    Ow, Andrew; Tan, Winston; Pienkowski, Lukasz

    2016-09-01

    The use of virtual surgical planning and computer-aided design/computer-aided manufacturing has been reported to enhance the planning for the reconstruction of mandibular continuity defects. This case report illustrates the use of this technology in the fabrication of a custom-made titanium prosthesis to restore a segmental mandibular defect. The design specifications and sequence of the custom-made titanium prosthesis are discussed. Although successful in this case, there are limitations in its application and case selection is of vital importance. PMID:27516841

  6. Computer-aided design and drafting visualization of anatomical structure of the human eye and orbit

    NASA Astrophysics Data System (ADS)

    Parshall, Robert F.; Sadler, Lewis L.

    1991-04-01

    A generalized " anatomically standard" eyeball was geometrically modeled on a Computer-Aided Design and Drafting (CADD) workstation based on published conceptual norms of dimension radii of curvature alignments etc. An orbital environment for this model was concurrently prepared by serial section reconstruction of a cadaver specimen. Issues addressed include orienting unregistered sections the utility of interactive CADDsupported visual logic in interpretive decision making and the value of geometric models.

  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. Glycoscience -- a new frontier in rational drug design.

    PubMed

    Gornik, Olga; Dumić, Jerka; Flogel, Mirna; Lauc, Gordan

    2006-03-01

    Glycans are the most abundant and most diverse biopolymers in nature. Because of their highly specific interactions with physiological receptors, they participate in many crucial biological processes. All these processes are potential targets for therapeutic intervention, and carbohydrate-based drugs are rapidly being taken up by the modern biotechnology and pharmaceutical industry. Recent developments in the field of glycobiology have overcome the problem of glycan analysis and synthesis; and many compounds based on carbohydrates are now in various stages of clinical trials. This article presents glycoproteins in a new light, as an important biopharmaceutical target, giving an overview of their potential use as therapeutic glycoproteins and proteoglycans, inflammation blockers, cancer therapeutics and vaccines, inhibitors of pathogenic microbes, viral inhibitors and potential aids in the treatment of lysosomal diseases, neurological diseases and transplantation rejection. PMID:16613732

  10. Drug treatments for schizophrenia: pragmatism in trial design shows lack of progress in drug design.

    PubMed

    Cheng, F; Jones, P B

    2013-09-01

    Aims. The introduction of second generation antipsychotic (SGA) medication over a decade ago led to changes in prescribing practices; these drugs have eclipsed their predecessors as treatments for schizophrenia. However, the metabolic side effects of these newer antipsychotics have been marked and there are increasing concerns as to whether these novel drugs really are superior to their predecessors in terms of the balance between risks and benefits. In this article, we review the literature regarding comparisons between first generation antipsychotic (FGA) and SGA in terms of clinical effectiveness. Methods. Large (n > 150) randomized-controlled trials (RCTs) comparing the effectiveness (efficacy and side effects) of FGA and SGA medications other than clozapine were reviewed, as were meta-analyses that included smaller studies. Results. The superiority in efficacy and reduced extrapyramidal side effects (EPSE) of SGAs is modest, especially when compared with low-dose FGAs. However, the high risk of weight gain and other metabolic disturbances associated with certain SGAs such as olanzapine is markedly higher than the risk with FGAs at the doses used in the trials. Conclusions. The efficacy profiles of various FGAs and SGAs are relatively similar, but their side effects vary between and within classes. Overall, large pragmatic trials of clinical effectiveness indicate that the care used in prescribing and managing drug treatments to ensure tolerability may be more important than the class of drug used. PMID:23388168

  11. Semantic Web Ontology and Data Integration: a Case Study in Aiding Psychiatric Drug Repurposing.

    PubMed

    Liang, Chen; Sun, Jingchun; Tao, Cui

    2016-01-01

    Despite ongoing progress towards treating mental illness, there remain significant difficulties in selecting probable candidate drugs from the existing database. We describe an ontology - oriented approach aims to represent the nexus between genes, drugs, phenotypes, symptoms, and diseases from multiple information sources. Along with this approach, we report a case study in which we attempted to explore the candidate drugs that effective for both bipolar disorder and epilepsy. We constructed an ontology that incorporates the knowledge between the two diseases and performed semantic reasoning task on the ontology. The reasoning results suggested 48 candidate drugs that hold promise for a further breakthrough. The evaluation was performed and demonstrated the validity of the proposed ontology. The overarching goal of this research is to build a framework of ontology - based data integration underpinning psychiatric drug repurposing. This approach prioritizes the candidate drugs that have potential associations among genes, phenotypes and symptoms, and thus facilitates the data integration and drug repurposing in psychiatric disorders. PMID:27570661

  12. 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.

  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. Nanoassembly of surfactants with interfacial drug-interactive motifs as tailor-designed drug carriers.

    PubMed

    Gao, Xiang; Huang, Yixian; Makhov, Alexander M; Epperly, Michael; Lu, Jianqin; Grab, Sheila; Zhang, Peijun; Rohan, Lisa; Xie, Xiang-Qun; Wipf, Peter; Greenberger, Joel; Li, Song

    2013-01-01

    PEGylated lipopeptide surfactants carrying drug-interactive motifs specific for a peptide-nitroxide antioxidant, JP4-039, were designed and constructed to facilitate the solubilization of this drug candidate as micelles and emulsion nanoparticles. A simple screening process based on the ability that prevents the formation of crystals of JP4-039 in aqueous solution was used to identify agents that have potential drug-interactive activities. Several protected lysine derivatives possessing this activity were identified, of which α-Fmoc-ε-t-Boc lysine is the most potent, followed by α-Cbz- and α-iso-butyloxycarbonyl-ε-t-Boc-lysine. Using a polymer-supported liquid-phase synthesis approach, a series of synthetic lipopeptide surfactants with PEG headgroup, varied numbers and geometries of α-Fmoc or α-Cbz-lysyl groups located at interfacial region as the drug-interactive domains, and oleoyl chains as the hydrophobic tails were synthesized. All α-Fmoc-lysyl-containing lipopeptide surfactants were able to solubilize JP4-039 as micelles, with enhanced solubilizing activity for surfactants with increased numbers of α-Fmoc groups. The PEGylated lipopeptide surfactants with α-Fmoc-lysyl groups alone tend to form filamentous or wormlike micelles. The presence of JP4-039 transformed α-Fmoc-containing filamentous micelles into dots and barlike mixed micelles with substantially reduced sizes. Fluorescence quenching and NMR studies revealed that the drug and surfactant molecules were in close proximity in the complex. JP4-039-loaded emulsion carrying α-Cbz-containing surfactants demonstrated enhanced stability over drug-loaded emulsion without lipopeptide surfactants. JP4-039 emulsion showed a significant mitigation effect on mice exposed to a lethal dose of radiation. PEGylated lipopeptides with an interfacially located drug-interactive domain are therefore tailor-designed formulation materials potentially useful for drug development. PMID:23244299

  15. Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir – insights for drug design

    PubMed Central

    Weber, Irene T.; Waltman, Mary Jo; Mustyakimov, Marat; Blakeley, Matthew P.; Keen, David A.; Ghosh, Arun K.; Langan, Paul; Kovalevsky, Andrey Y.

    2013-01-01

    HIV-1 protease is an important target for the development of antiviral inhibitors to treat AIDS. A room-temperature joint X-ray/neutron structure of the protease in complex with clinical drug amprenavir has been determined at 2.0 Å resolution. The structure provides direct determination of hydrogen atom positions in the enzyme active site. Analysis of the enzyme-drug interactions suggests that some hydrogen bonds may be weaker than deduced from the non-hydrogen interatomic distances. This information may be valuable for the design of improved protease inhibitors. PMID:23772563

  16. 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. PMID:23217358

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

    PubMed

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

    2011-02-01

    The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse. PMID:21441120

  18. Computer-aided ergonomics: a case study of incorporating ergonomics analyses into workplace design.

    PubMed

    Feyen, R; Liu, Y; Chaffin, D; Jimmerson, G; Joseph, B

    2000-06-01

    One of the primary goals of computer-aided ergonomics is to develop software tools that allow ergonomics information to be accessed at the earliest stages of design. This case study discusses a PC-based software program that allows a designer to quantify a worker's biomechanical risk for injury based on a proposed workplace design. The program couples an established software tool for biomechanical analysis, the Three-Dimensional Static Strength Prediction Program (3DSSPP), with a widely used computer-aided design software package, AutoCAD. The use of this "3DSSPP/AutoCAD interface" in the proactive analysis of an automotive assembly task is described and the results compared with an independent assessment using observations of workers performing the same task. Both studies yield similar conclusions, suggesting that proactive use of software such as the 3DSSPP/AutoCAD interface may be a valid tool in evaluating proposed workplace designs. In this context, issues in the analysis of workplace designs regarding the use of supporting ergonomic tools, assumptions, and posture selection are discussed. PMID:10855452

  19. Design and Focus Test of a Preconsultation Decision Aid for Breast Cancer Reconstruction Patients: A Quality Improvement Initiative

    PubMed Central

    Hui, Kenneth J.; Liu, Xiang X.; Luan, Anna

    2015-01-01

    Objective: To design, develop, and evaluate via focus group a preconsultation decision aid to improve patient satisfaction for breast reconstruction. Methods: The design of the decision aid was based on perceived patient needs, literature, existing decision aids, and current standard of breast cancer reconstruction treatment and consultation at Stanford. Our decision aid was designed to (1) reducing fear of the unknown in patients via providing a knowledge base that they can rely on, (2) helping patients identify their key breast reconstruction concerns, (3) addressing common patient concerns, (4) providing a framework to help patients identify the treatment option that may be right for them, and (5) promoting shared decision making. Physicians were consulted on the decision aid, following which a focus group was conducted for patient feedback. Results: Interviewed patients (n = 12) were supportive of the decision aid initiative. Participants were especially pleased with the side-by-side comparison of surgical options and the parsimonious way information was represented. All patients before undergoing reconstruction (n = 3) requested the decision guide to reference at home. All interviewed patients believed information level was “about right.” Conclusions: Decision aid was well received by patients in the focus group. As the initiative is for quality improvement, we saw no need to further delay the distribution of the decision aid. A pilot study will be conducted to evaluate whether our decision aid has an effect on patients’ decision regret, stress, and anxiety. PMID:26171096

  20. Improving drug retention in liposomes by aging with the aid of glucose.

    PubMed

    Zhang, Wenli; Falconer, James R; Baguley, Bruce C; Shaw, John P; Kanamala, Manju; Xu, Hongtao; Wang, Guangji; Liu, Jianping; Wu, Zimei

    2016-05-30

    This paper describes a novel method to improve drug retention in liposomes for the poorly water-soluble (lipophilic) model drug asulacrine (ASL). ASL was loaded in the aqueous phase of liposomes and the effects of aging conditions and drug loading levels on drug retention were investigated using an in vitro bio-relevant drug release test established in this study. The status of intra-liposomal drug was investigated using differential scanning calorimetry (DSC) and cryo-transmission electron microscopy (cryo-TEM). Pharmacokinetics and venous tolerance of the formulations were simultaneously studied in rabbits following one-hour intravenous infusion via the ear vein. The presence of glucose during aging was found to be crucial to accelerate drug precipitation and to stabilize the liposomal membrane with high drug loading (8.9% over 4.5% w/w) as a prerequisite. Although no drug crystals were detected, DSC showed a lower phase-transition peak in the glucose-assisted aged ASL-liposomes, indicating interaction of phospholipids with the sugar. Cryo-TEM revealed more 'coffee bean' like drug precipitate in the ASL-liposomes aged in the glucose solution. In rabbits, these liposomes gave rise to a 1.9 times longer half-life than the fresh liposomes, with no venous irritation observed. Inducing and stabilizing drug precipitation in the liposome cores by aging in the presence of sugar provided an easy approach to improve drug retention in liposomes. The study also highlighted the importance of bio-relevance of in vitro release methods to predict in vivo drug release. PMID:27021465

  1. 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...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species...

  3. 21 CFR 516.30 - Annual reports for a MUMS-designated drug.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (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...

  4. 21 CFR 516.28 - Publication of MUMS-drug designations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... FDA will periodically update a publicly available list of MUMS-designated drugs. This list will be... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Publication of MUMS-drug designations. 516.28 Section 516.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  5. 21 CFR 516.28 - Publication of MUMS-drug designations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... FDA will periodically update a publicly available list of MUMS-designated drugs. This list will be... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Publication of MUMS-drug designations. 516.28 Section 516.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  6. Update and Overview of Practical Epidemiologic Aspects of HIV/AIDS among Injection Drug Users in the United States

    PubMed Central

    Garfein, Richard S.; Swartzendruber, Andrea; Purcell, David W.; Paxton, Lynn A.; Greenberg, Alan E.

    2006-01-01

    In a changing public health landscape in which local, state, and federal agencies must confront threats of bioterrorism, emerging infections, and numerous chronic diseases, transmission of HIV among injection drug users (IDUs) continues to be an important public health issue and one of the driving forces behind the HIV epidemic. Using a computerized MEDLINE search of published articles from January 1981 through October 2005, we conducted a literature review of practical epidemiologic aspects of HIV/AIDS among IDUs in the United States. Although recent trends indicate a decline in the proportion of newly diagnosed HIV infections associated with injection drug use, drug-use behaviors overall still account for 32% of new HIV diagnoses. Factors in addition to syringe sharing contribute to HIV transmission among IDUs: risky sexual behaviors, sharing of drug preparation equipment and drug solutions, and contextual and social factors. Promising approaches for HIV prevention include rapid HIV testing, office-based substance abuse treatment, behavioral interventions, improved communication about syringe exchange programs, and case management. HIV among IDUs continues to be an important public health problem in the 21st century. It is imperative that public health agencies continue to monitor and combat the HIV epidemic among IDUs to ensure that hard-won gains will not be eroded. PMID:16736357

  7. 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.

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

    PubMed Central

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

    2015-01-01

    The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. PMID:25765758

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

    PubMed

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

    2015-04-13

    The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. PMID:25765758

  10. 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.

  11. 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. PMID:26262350

  12. Chemogenomic profiling of Plasmodium falciparum as a tool to aid antimalarial drug discovery

    PubMed Central

    Pradhan, Anupam; Siwo, Geoffrey H.; Singh, Naresh; Martens, Brian; Balu, Bharath; Button-Simons, Katrina A.; Tan, Asako; Zhang, Min; Udenze, Kenneth O.; Jiang, Rays H.Y.; Ferdig, Michael T.; Adams, John H.; Kyle, Dennis E.

    2015-01-01

    The spread of Plasmodium falciparum multidrug resistance highlights the urgency to discover new targets and chemical scaffolds. Unfortunately, lack of experimentally validated functional information about most P. falciparum genes remains a strategic hurdle. Chemogenomic profiling is an established tool for classification of drugs with similar mechanisms of action by comparing drug fitness profiles in a collection of mutants. Inferences of drug mechanisms of action and targets can be obtained by associations between shifts in drug fitness and specific genetic changes in the mutants. In this screen, P. falciparum, piggyBac single insertion mutants were profiled for altered responses to antimalarial drugs and metabolic inhibitors to create chemogenomic profiles. Drugs targeting the same pathway shared similar response profiles and multiple pairwise correlations of the chemogenomic profiles revealed novel insights into drugs’ mechanisms of action. A mutant of the artemisinin resistance candidate gene - “K13-propeller” gene (PF3D7_1343700) exhibited increased susceptibility to artemisinin drugs and identified a cluster of 7 mutants based on similar enhanced responses to the drugs tested. Our approach of chemogenomic profiling reveals artemisinin functional activity, linked by the unexpected drug-gene relationships of these mutants, to signal transduction and cell cycle regulation pathways. PMID:26541648

  13. 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.

  14. 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.

  15. Analysis of Drug Design for a Selection of G Protein-Coupled Neuro- Receptors Using Neural Network Techniques.

    PubMed

    Agerskov, Claus; Mortensen, Rasmus M; Bohr, Henrik G

    2015-01-01

    A study is presented on how well possible drug-molecules can be predicted with respect to their function and binding to a selection of neuro-receptors by the use of artificial neural networks. The ligands investigated in this study are chosen to be corresponding to the G protein-coupled receptors µ-opioid, serotonin 2B (5-HT2B) and metabotropic glutamate D5. They are selected due to the availability of pharmacological drug-molecule binding data for these receptors. Feedback and deep belief artificial neural network architectures (NNs) were chosen to perform the task of aiding drugdesign. This is done by training on structural features, selected using a "minimum redundancy, maximum relevance"-test, and testing for successful prediction of categorized binding strength. An extensive comparison of the neural network performances was made in order to select the optimal architecture. Deep belief networks, trained with greedy learning algorithms, showed superior performance in prediction over the simple feedback NNs. The best networks obtained scores of more than 90 % accuracy in predicting the degree of binding drug molecules to the mentioned receptors and with a maximal Matthew`s coefficient of 0.925. The performance of 8 category networks (8 output classes for binding strength) obtained a prediction accuracy of above 60 %. After training the networks, tests were done on how well the systems could be used as an aid in designing candidate drug molecules. Specifically, it was shown how a selection of chemical characteristics could give the lowest observed IC50 values, meaning largest bio-effect pr. nM substance, around 0.03-0.06 nM. These ligand characteristics could be total number of atoms, their types etc. In conclusion, deep belief networks trained on drug-molecule structures were demonstrated as powerful computational tools, able to aid in drug-design in a fast and cheap fashion, compared to conventional pharmacological techniques. PMID:26463104

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

    PubMed

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

    2016-04-25

    Computer-aided drug design plays an important role in medicinal chemistry to obtain insights into molecular mechanisms and to prioritize design strategies. Although significant improvement has been made in structure based design, it still remains a key challenge to accurately model and predict induced fit mechanisms. Most of the current available techniques either do not provide sufficient protein conformational sampling or are too computationally demanding to fit an industrial setting. The current study presents a systematic and exhaustive investigation of predicting binding modes for a range of systems using PELE (Protein Energy Landscape Exploration), an efficient and fast protein-ligand sampling algorithm. The systems analyzed (cytochrome P, kinase, protease, and nuclear hormone receptor) exhibit different complexities of ligand induced fit mechanisms and protein dynamics. The results are compared with results from classical molecular dynamics simulations and (induced fit) docking. This study shows that ligand induced side chain rearrangements and smaller to medium backbone movements are captured well in PELE. Large secondary structure rearrangements, however, remain challenging for all employed techniques. Relevant binding modes (ligand heavy atom RMSD < 1.0 Å) can be obtained by the PELE method within a few hours of simulation, positioning PELE as a tool applicable for rapid drug design cycles. PMID:26974351

  17. Informal Caregiver Characteristics Associated with Viral Load Suppression Among Current or Former Injection Drug Users Living with HIV/AIDS.

    PubMed

    Mitchell, Mary M; Robinson, Allysha C; Nguyen, Trang Q; Knowlton, Amy R

    2015-11-01

    Few studies have examined the association between having an informal (unpaid) caregiver and viral suppression among persons living with HIV/AIDS (PLHIV) who are on antiretroviral therapy. The current study examined relationships between caregivers' individual and social network characteristics and care recipient viral suppression. Baseline data were from the BEACON study caregivers and their HIV seropositive former or current drug using care recipients, of whom 89 % were African American (N = 258 dyads). Using adjusted logistic regression, care recipient's undetectable viral load was positively associated with caregiver's limited physical functioning and negatively associated with caregivers having few family members to turn to for problem solving, a greater number of current drug users in their network, and poorer perceptions of the care recipient's mental health. Results further understandings of interpersonal relationship factors important to PLHIV's health outcomes, and the need for caregiving relationship-focused intervention to promote viral suppression among PLHIV. PMID:25969180

  18. 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

  19. 21 CFR 516.20 - Content and format of a request for MUMS-drug designation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.20 Content and format of a request for MUMS-drug designation. (a) A sponsor that submits a request for designation of a new...

  20. 21 CFR 516.20 - Content and format of a request for MUMS-drug designation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.20 Content and format of a request for MUMS-drug designation. (a) A sponsor that submits a request for designation of a new...

  1. 21 CFR 516.20 - Content and format of a request for MUMS-drug designation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.20 Content and format of a request for MUMS-drug designation. (a) A sponsor that submits a request for designation of a new...

  2. Design principles of chemical penetration enhancers for transdermal drug delivery

    PubMed Central

    Karande, Pankaj; Jain, Amit; Ergun, Kaitlin; Kispersky, Vincent; Mitragotri, Samir

    2005-01-01

    Chemical penetration enhancers (CPEs) are present in a large number of transdermal, dermatological, and cosmetic products to aid dermal absorption of curatives and aesthetics. This wide spectrum of use is based on only a handful of molecules, the majority of which belong to three to four typical chemical functionalities, sporadically introduced as CPEs in the last 50 years. Using >100 CPEs representing several chemical functionalities, we report on the fundamental mechanisms that determine the barrier disruption potential of CPEs and skin safety in their presence. Fourier transform infrared spectroscopy studies revealed that regardless of their chemical make-up, CPEs perturb the skin barrier via extraction or fluidization of lipid bilayers. Irritation response of CPEs, on the other hand, correlated with the denaturation of stratum corneum proteins, making it feasible to use protein conformation changes to map CPE safety in vitro. Most interestingly, the understanding of underlying molecular forces responsible for CPE safety and potency reveals inherent constraints that limit CPE performance. Reengineering this knowledge back into molecular structure, we designed >300 potential CPEs. These molecules were screened in silico and subsequently tested in vitro for molecular delivery. These molecules significantly broaden the repertoire of CPEs that can aid the design of optimized transdermal, dermatological, and cosmetic formulations in the future. PMID:15774584

  3. 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…

  4. Evaluation of computer-aided design and drafting for the electric power industry. Final report

    SciTech Connect

    Anuskiewicz, T.; Barduhn, G.; Lowther, B.; Osman, I.

    1984-01-01

    This report reviews current and future computer-aided design and drafting (CADD) technology relative to utility needs and to identify useful development projects that may be undertaken by EPRI. The principal conclusions are that computer aids offer substantial cost and time savings and that computer systems are being developed to take advantage of the savings. Data bases are not available for direct communication between computers used by the power industry and will limit benefits to the industry. Recommendations are made for EPRI to take the initiative to develop the data bases for direct communication between power industry computers and to research, develop, and demonstrate new applications within the industry. Key components of a CADD system are described. The state of the art of two- and three-dimensional CADD systems to perform graphics and project management control functions are assessed. Comparison is made of three-dimensional electronic models and plastic models.

  5. 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.

  6. Hearing Aid

    MedlinePlus

    ... and Food and Drug Administration Staff FDA permits marketing of new laser-based hearing aid with potential ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  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. 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.

  9. Design-based approach to ethics in computer-aided diagnosis

    NASA Astrophysics Data System (ADS)

    Collmann, Jeff R.; Lin, Jyh-Shyan; Freedman, Matthew T.; Wu, Chris Y.; Hayes, Wendelin S.; Mun, Seong K.

    1996-04-01

    A design-based approach to ethical analysis examines how computer scientists, physicians and patients make and justify choices in designing, using and reacting to computer-aided diagnosis (CADx) systems. The basic hypothesis of this research is that values are embedded in CADx systems during all phases of their development, not just retrospectively imposed on them. This paper concentrates on the work of computer scientists and physicians as they attempt to resolve central technical questions in designing clinically functional CADx systems for lung cancer and breast cancer diagnosis. The work of Lo, Chan, Freedman, Lin, Wu and their colleagues provides the initial data on which this study is based. As these researchers seek to increase the rate of true positive classifications of detected abnormalities in chest radiographs and mammograms, they explore dimensions of the fundamental ethical principal of beneficence. The training of CADx systems demonstrates the key ethical dilemmas inherent in their current design.

  10. The Impact of State AIDS Drug Assistance Policies on Clinical and Economic Outcomes of People With HIV.

    PubMed

    Snider, Julia Thornton; Goldman, Dana P; Rosenblatt, Lisa; Seekins, Daniel; Juday, Timothy; Sanchez, Yuri; Wu, Yanyu; Peneva, Desi; Romley, John A

    2016-06-01

    We investigated the effect of changes to state AIDS Drug Assistance Programs (ADAP) policies, which govern access to antiretroviral therapy (ART), on clinical and economic outcomes among low-income people living with HIV/AIDS. Retrospective analyses of ART access were conducted on state ADAP policies, using data from ADAP Monitoring Reports and Kaiser Family Foundation from 2006 to 2010. We found stricter eligibility requirements reduce the number of HIV-positive individuals with ART access through ADAP, and decreased ART use increases mortality by 2.67 quality-adjusted life years (QALYs) per beneficiary. If the ADAP income eligibility cutoff were decreased by 50 percentage points in each state, 4,626 individuals would lose ART access nationwide. Based on a $22,143 cost/QALY, this policy would save $274 million in health care expenditures (2012 dollars), but result in 12,352 QALYs lost, valued at $1.2 billion. Therefore, states should exercise caution in restricting programs that increase ART access for low-income people living with HIV/AIDS. PMID:26537525

  11. 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. PMID:25256222

  12. Cyclotides: macrocyclic peptides with applications in drug design and agriculture.

    PubMed

    Craik, David J; Mylne, Joshua S; Daly, Norelle L

    2010-01-01

    Cyclotides are disulfide-rich peptides from plants that are exceptionally stable as a result of their unique cyclic cystine knot structural motif. Their natural role is thought to be as plant defence agents, most notably against insect pests, but they also have potential applications in drug design and agriculture. This article identifies gaps in current knowledge on cyclotides and suggests future directions for research into this fascinating family of ultra-stable mini-proteins. PMID:19795188

  13. 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.

  14. Emerging paradigms in anti-infective drug design.

    PubMed

    Barrett, Michael P; Croft, Simon L

    2014-01-01

    The need for new drugs to treat microbial infections is pressing. The great progress made in the middle part of the twentieth Century was followed by a period of relative inactivity as the medical needs relating to infectious disease in the wealthier nations receded. Growing realisation that anti-infectives are needed in many parts of the world, to treat neglected diseases as well as to combat the burgeoning risk of resistance to existing drugs, has galvanised a new wave of research into anti-microbial drugs. The transfer of knowledge from the Pharmaceutical industry relating to the importance of understanding how to target drugs successfully within the body, and improved understanding of how pathogens interact with their hosts, is driving a series of new paradigms in anti-infective drug design. Here we provide an overview of those processes as an introduction to a series of articles from experts in this area that emerged from a meeting entitled "Emerging Paradigms in Anti-Infective Drug Design" held in London on the 17th and 18th September 2012. The symposium was organised jointly by British Society for Parasitology (BSP) and the Biological & Medicinal Chemistry sector of the Royal Society of Chemistry (RSC) and held at the London School of Hygiene & Tropical Medicine. The symposium set out to cover all aspects of the identification of new therapeutic modalities for the treatment of neglected and tropical diseases. We aimed to bring together leading scientists from all the disciplines working in this field and cover the pharmacology, medicinal chemistry and drug delivery of potential new medicines. Sessions were held on: "Target diseases and targets for drugs", "Target based medicinal chemistry", "Bioavailability and chemistry", "Targeting intracellular microbes", "Alternative approaches and models", and "New anti-infectives - how do we get there?" This symposium was organised by Simon Croft (LSHTM) and Mike Barrett (University of Glasgow) for the BSP, and David

  15. 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

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

    PubMed

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

    2015-01-01

    Fragment-based drug discovery (FBDD) has caused a revolution in the process of drug discovery and design, with many FBDD leads being developed into clinical trials or approved in the past few years. Compared with traditional high-throughput screening, it displays obvious advantages such as efficiently covering chemical space, achieving higher hit rates, and so forth. In this review, we focus on the most recent developments of FBDD for improving drug discovery, illustrating the process and the importance of FBDD. In particular, the computational strategies applied in the process of FBDD and molecular-docking programs are highlighted elaborately. In most cases, docking is used for predicting the ligand-receptor interaction modes and hit identification by structurebased virtual screening. The successful cases of typical significance and the hits identified most recently are discussed. PMID:25420726

  17. Leadless chip carrier packaging and CAD/CAM (Computer-Aided Design/Computer-Aided Manufacturing) supported wire wrap interconnect technology for subnanosecond ECL (Emitter Coupled Logic)

    NASA Astrophysics Data System (ADS)

    Gilbert, B. K.

    1982-12-01

    This document is the third year interim report for a four-year program to refine and develop Computer-Aided Design protocols for implementation of subnanosceond Emitter Coupled Logic in High-Speed Computer Modules using a wire wrap interconnection medium. The software and user manual for implementation guides are not part of the actual report. This report describes the results of work conducted in the third year of a four year program to develop rapid methods for designing and prototyping high-speed digital processor systems using subnanosecond emitter coupled logic (ECL). The third year effort was divided into two separate sets of tasks. In Task 1, described in Sections 3 - 7 of this report, we have nearly completed development of new sets of design rules, interconnection protocols, special components, and logic panels, for a technology based upon specially designed leadless ceramic chip carriers developed at Mayo Foundation. Task 2, described in Sections 8 and IX of this report, continued the development of a comprehensive computer-aided design/computer-aided manufacturing (CAD/CAM) software package which is specifically tailored to support the peculiar design requirements of processors operating in a high clock rate, transmission line environment, either with subnanosecond ECL components or with any other families of subnanosecond devices.

  18. Identification of levothyroxine antichagasic activity through computer-aided drug repurposing.

    PubMed

    Bellera, Carolina L; Balcazar, Darío E; Alberca, Lucas; Labriola, Carlos A; Talevi, Alan; Carrillo, Carolina

    2014-01-01

    Cruzipain (Cz) is the major cysteine protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. A conformation-independent classifier capable of identifying Cz inhibitors was derived from a 163-compound dataset and later applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 3 of which were acquired and tested on Cz and T. cruzi epimastigotes proliferation. Among them, levothyroxine, traditionally used in hormone replacement therapy in patients with hypothyroidism, showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite. PMID:24592161

  19. 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

  20. Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

    NASA Astrophysics Data System (ADS)

    Kurtoglu, Yunus Emre

    The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.