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

Science.gov (United States)

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.

Market design for rapid demand response

DEFF Research Database (Denmark)

Nielsen, Kurt; Tamirat, Tseganesh Wubale

We suggest a market design for rapid demand response in electricity markets. The solution consists of remotely controlled switches, meters, forecasting models as well as a flexible auction market to set prices and select endusers job by job. The auction market motivates truth-telling and makes...... it simple to involve the endusers in advance and to activate demand response immediately. The collective solution is analyzed and economic simulations are conducted for the case of Kenya. Kenya has been su ering from unreliable electricity supply for many years and companies and households have learned...... to adjust by investments in backup generators. We focus on turning the many private backup generators into a demand response system. The economic simulation focuses on possible distortion introduced by various ways of splitting the generated surplus from the demand response system. An auction run instantly...

The elasticity of drugs demand in Colombia’s pharmaceutical market

Directory of Open Access Journals (Sweden)

Johanna Vásquez Velásquez

2013-06-01

Full Text Available Based on a dynamic specification of the AIDS model arisen from cointegration techniques, this research estimated the elasticity of the intra-molecular, brand and generic demand for three tracer conditions: essential hypertension, diabetes and hyperlipidemia both in the non-profit and private Colombian market. The estimate of the intra-molecular demand elasticity allows us to conclude that both brand-name and generic drugs are inelastic to price changes, they are luxury goods according to expenditure elasticity and intra-molecular replacement seems to exist due to the elasticity of substitution.

Architecture design of reconfigurable accelerators for demanding apllications.

NARCIS (Netherlands)

Jozwiak, L.; Jan, Y.

2010-01-01

This paper focuses on mastering the architecture development of reconfigurable hardware accelerators for highly demanding applications. It presents the results of our analysis of the main issues that have to be addressed when designing accelerators for demanding applications, when using as an

Design of hardware accelerators for demanding applications.

NARCIS (Netherlands)

Jozwiak, L.; Jan, Y.

2010-01-01

This paper focuses on mastering the architecture development of hardware accelerators. It presents the results of our analysis of the main issues that have to be addressed when designing accelerators for modern demanding applications, when using as an example the accelerator design for LDPC decoding

Repetitive on-demand drug release from polymeric matrices containing a macroscopic spherical iron core.

Science.gov (United States)

Rovers, Stefan A; Kemmere, Maartje F; Keurentjes, Jos T F; Hoogenboom, Richard

2017-09-15

A system for multiple on-demand drug release has been prepared that can be activated with an alternating magnetic field as external trigger. The core/shell samples have been developed based on a macroscopic spherical iron core coated with a thermoresponsive polymer, poly(styrene-stat-butyl methacrylate), containing ibuprofen as a model drug. During exposure of the samples to the magnetic field (ON state), the release rate of ibuprofen is significantly increased, up to 35 times the release rate without the magnetic field (OFF state). Using one sample or two samples in line with the magnetic field does not influence the ON/OFF ratio of the system, showing the possibility of using multiple samples to increase and tune the drug dose. Increasing the concentration of ibuprofen in the polymer layer is shown to increase the release rate in both the ON and OFF states. Increasing the size of the iron core and, consequently, decreasing the polymer thickness, was found to only increase the release rate during exposure resulting in higher ON/OFF ratios. The developed on demand drug delivery systems represents a promising development towards on demand drug delivery implants. During my chemical engineering studies, it was only during my master thesis work that I decided to continue with PhD research as I really enjoyed doing original research. When coming to the end of my PhD research under supervision of Prof. Ulrich S. Schubert, I developed the ambition to pursue an academic career. Fortunately, I got the opportunity to stay with Prof. Schubert as project leader for the Dutch Polymer Institute (DPI). Within this position, I supervised ten researchers and was able to start developing my independent research lines. Despite that I now advise students to not stay in the same laboratory, this first position allowed me to gain some initial independence and to publish a large number of papers that has been a great benefit in my further career. After two and a half years I needed a new

Design and Implementation of Demand Response Information Interactive Service Platform Based on “Internet Plus” Smart Energy

Science.gov (United States)

Cui, Gaoying; Fan, Jie; Qin, Yuchen; Wang, Dong; Chen, Guangyan

2017-05-01

In order to promote the effective use of demand response load side resources, promote the interaction between supply and demand, enhance the level of customer service and achieve the overall utilization of energy, this paper briefly explain the background significance of design demand response information platform and current situation of domestic and foreign development; Analyse the new demand of electricity demand response combined with the application of Internet and big data technology; Design demand response information platform architecture, construct demand responsive system, analyse process of demand response strategy formulate and intelligent execution implement; study application which combined with the big data, Internet and demand response technology; Finally, from information interaction architecture, control architecture and function design perspective design implementation of demand response information platform, illustrate the feasibility of the proposed platform design scheme implemented in a certain extent.

The design of optimal electric power demand management contracts

Science.gov (United States)

Fahrioglu, Murat

1999-11-01

Our society derives a quantifiable benefit from electric power. In particular, forced outages or blackouts have enormous consequences on society, one of which is loss of economic surplus. Electric utilities try to provide reliable supply of electric power to their customers. Maximum customer benefit derives from minimum cost and sufficient supply availability. Customers willing to share in "availability risk" can derive further benefit by participating in controlled outage programs. Specifically, whenever utilities foresee dangerous loading patterns, there is a need for a rapid reduction in demand either system-wide or at specific locations. The utility needs to get relief in order to solve its problems quickly and efficiently. This relief can come from customers who agree to curtail their loads upon request in exchange for an incentive fee. This thesis shows how utilities can get efficient load relief while maximizing their economic benefit. This work also shows how estimated customer cost functions can be calibrated, using existing utility data, to help in designing efficient demand management contracts. In order to design such contracts, optimal mechanism design is adopted from "Game Theory" and applied to the interaction between a utility and its customers. The idea behind mechanism design is to design an incentive structure that encourages customers to sign up for the right contract and reveal their true value of power. If a utility has demand management contracts with customers at critical locations, most operational problems can be solved efficiently. This thesis illustrates how locational attributes of customers incorporated into demand management contract design can have a significant impact in solving system problems. This kind of demand management contracts can also be used by an Independent System Operator (ISO). During times of congestion a loss of economic surplus occurs. When the market is too slow or cannot help relieve congestion, demand management

A dawning demand for a new cannabis policy: A study of Swedish online drug discussions.

Science.gov (United States)

Månsson, Josefin

2014-07-01

This study examines how online discussions on drug policy are formulating an oppositional cannabis discourse in an otherwise prohibitionist country like Sweden. The focus of the paper is to identify demands for an alternative cannabis policy as well as analysing how these demands are linked to governance. The empirical material is 56 discussion-threads from the online message-board Flashback Forum that were active during the first eight months of 2012. Discourse theory was used to locate the discourse, and governmentality theory was used to locate the political belonging of the discourse. On Flashback Forum demands for a new cannabis policy are articulated in opposition to Swedish prohibitionist discourse. The oppositional discourse is constructed around the nodal points cannabis, harm, state and freedom that fill legalisation/decriminalisation/liberalisation with meaning. The nodal points are surrounded by policy demands that get their meaning through the particular nodal. These demands originate from neo-liberal and welfarist political rationalities. Neo-liberal and welfarist demands are mixed, and participants are simultaneously asking for state and individual approaches to handle the cannabis issue. Swedish online discourse on cannabis widens the scope beyond the confines of drug policy to broader demands such as social justice, individual choice and increased welfare. These demands are not essentially linked together and many are politically contradictory. This is also significant for the discourse; it is not hegemonised by a political ideology. The discourse is negotiated between the neo-liberal version of an alternative policy demanding individual freedom, and the welfarist version demanding social responsibility. This implies the influence of the heritage from the social-democratic discourse, centred on state responsibility, which have been dominating Swedish politics in modern times. Consequently, this study refutes that the demand for a new cannabis

Deep-Learning-Enabled On-Demand Design of Chiral Metamaterials.

Science.gov (United States)

Ma, Wei; Cheng, Feng; Liu, Yongmin

2018-06-11

Deep-learning framework has significantly impelled the development of modern machine learning technology by continuously pushing the limit of traditional recognition and processing of images, speech, and videos. In the meantime, it starts to penetrate other disciplines, such as biology, genetics, materials science, and physics. Here, we report a deep-learning-based model, comprising two bidirectional neural networks assembled by a partial stacking strategy, to automatically design and optimize three-dimensional chiral metamaterials with strong chiroptical responses at predesignated wavelengths. The model can help to discover the intricate, nonintuitive relationship between a metamaterial structure and its optical responses from a number of training examples, which circumvents the time-consuming, case-by-case numerical simulations in conventional metamaterial designs. This approach not only realizes the forward prediction of optical performance much more accurately and efficiently but also enables one to inversely retrieve designs from given requirements. Our results demonstrate that such a data-driven model can be applied as a very powerful tool in studying complicated light-matter interactions and accelerating the on-demand design of nanophotonic devices, systems, and architectures for real world applications.

A Relook at the National Drug Control Strategy: Supply versus Demand

National Research Council Canada - National Science Library

Cook, Virgil

1998-01-01

.... By reviewing the ends, ways, and means of past drug control strategies, this paper suggests that it is time for the federal government to shift existing resources from supply reduction to demand reduction programs...

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

Directory of Open Access Journals (Sweden)

Apurv Patel

2016-01-01

Full Text Available 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.

Ion channel electrophysiology via integrated planar patch-clamp chip with on-demand drug exchange.

Science.gov (United States)

Chen, Chang-Yu; Tu, Ting-Yuan; Jong, De-Shien; Wo, Andrew M

2011-06-01

Planar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor-specific measurement and allowing rapid replacement of the cell-contacting aperture. Studies via endogenously expressed ion channels in HEK 293T cells were commenced to characterize the device. Results reveal the microfluidic concentration generator produces distinct solution/drug combination/concentrations on-demand. Volume-regulated chloride channel and voltage-gated potassium channels in HEK 293T cells immersed in generated solutions under various osmolarities or drug concentrations show unique channel signature under specific condition. Excitation and blockage of ion channels in a single cell was demonstrated via serial solution exchange. Robustness of the reversible bonding and ease of glass substrate replacement were proven via repeated usage of the integrated device. The present approach reveals the capability and flexibility of integrated microfluidic planar patch-clamp system for ion channel assays. Copyright © 2011 Wiley Periodicals, Inc.

Designer Drug Confusion: A Focus on MDMA.

Science.gov (United States)

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.…

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

Science.gov (United States)

2010-04-01

...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Timing of requests for orphan-drug designation..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan...

Sedative and Analgesic Drugs Online: A Content Analysis of the Supply and Demand Information Available in Thailand.

Science.gov (United States)

Pinyopornpanish, Kanokporn; Jiraporncharoen, Wichuda; Thaikla, Kanittha; Yoonut, Kulyapa; Angkurawaranon, Chaisiri

2018-03-21

Evidence from other countries has suggested that many controlled drugs are also offered online, even though it is illegal to sell these drugs without a license. To evaluate the current contents related to the supply and demand of sedatives and analgesic drugs available online in Thailand, with a particular focus on Facebook. A team of reviewers manually searched for data by entering keywords related to analgesic drugs and sedatives. The contents of the website were screened for supply and demand-related information. A total of 5,352 websites were found publicly available. The number of websites and Facebook pages containing the information potentially related to the supply and demand of analgesic drugs and sedatives was limited. Nine websites sold sedatives, and six websites sold analgesics directly. Fourteen Facebook pages were found, including 7 sedative pages and 7 analgesic pages. Within one year, the three remaining active pages multiplied in the number of followers by three- to nine-fold. The most popular Facebook page had over 2,900 followers. Both the internet and social media contain sites and pages where sedatives and analgesics are illegally advertised. These websites are searchable through common search engines. Although the number of websites is limited, the number of followers on these Facebook pages does suggest a growing number of people who are interested in such pages. Our study emphasized the importance of monitoring and developing potential plans relative to the online marketing of prescription drugs in Thailand.

A Masters Programme in Telecommunications Management--Demand-Based Curriculum Design

Science.gov (United States)

Gharaibeh, Khaled M.; Kaylani, Hazem; Murphy, Noel; Brennan, Conor; Itradat, Awni; Al-Bataineh, Mohammed; Aloqlah, Mohammed; Salhieh, Loay; Altarazi, Safwan; Rawashdeh, Nathir; del Carmen Bas Cerdá, María; Conchado Peiró, Andrea; Al-Zoubi, Asem; Harb, Bassam; Bany Salameh, Haythem

2015-01-01

This paper presents a curriculum design approach for a Masters Programme in Telecommunications Management based on demand data obtained from surveying the needs of potential students of the proposed programme. Through online surveys disseminated at telecom companies in Jordan, it was possible to measure the demand for such a programme and to…

Design of demand side response model in energy internet demonstration park

Science.gov (United States)

Zhang, Q.; Liu, D. N.

2017-08-01

The implementation of demand side response can bring a lot of benefits to the power system, users and society, but there are still many problems in the actual operation. Firstly, this paper analyses the current situation and problems of demand side response. On this basis, this paper analyses the advantages of implementing demand side response in the energy Internet demonstration park. Finally, the paper designs three kinds of feasible demand side response modes in the energy Internet demonstration park.

Opportunistic Wireless Charging System Design for an On-Demand Shuttle Service

Energy Technology Data Exchange (ETDEWEB)

Meintz, Andrew; Doubleday, Kate; Markel, Tony

2016-06-29

System right-sizing is critical to the implementation of in-motion wireless power transfer (WPT) for electric vehicles. This study evaluates potential system designs for an on-demand employee shuttle by determining the required battery size based on the rated power at a variable number of charging locations. Vehicle power and state of charge are simulated over the drive cycle, based on position and velocity data at every second from the existing shuttle. Adding just one WPT location can halve the battery size. Many configurations are capable of self-sustaining with WPT, while others benefit from supplemental stationary charging.

Information system design for demand-driven supply networks

OpenAIRE

Selk, Bernhard

2004-01-01

Information system design for demand-driven supply networks : integrating CRM & SCM / B. Selk, K. Turowski, C. Winnewisser. - In: EIS : Fourth International ICSC Symposium on Engineering of Intelligent Systems, EIS 2004. [Elektronische Ressource]. - Millet, Alberta : ICSC Interdisciplinary Research Canada, 2004. - 8 S. auf CD-ROM

Metabolism of designer drugs of abuse.

Science.gov (United States)

Staack, Roland F; Maurer, Hans H

2005-06-01

Abuse of designer drugs is widespread among young people, especially in the so-called "dance club scene" or "rave scene", worldwide. Severe and even fatal poisonings have been attributed to the consumption of such drugs of abuse. However, in contrast to new medicaments, which are extensively studied in controlled clinical studies concerning metabolism, including cytochrome P450 isoenzyme differentiation, and further pharmacokinetics, designer drugs are consumed without any safety testing. This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA) and 4-methylthioamphetamine (4-MTA), were taken into consideration as new "classical" amphetamine-derived designer drugs. Furthermore, N-benzylpiperazine (BZP), 1-(3, 4-methylenedioxybenzyl)piperazine (MDBP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP) were taken into consideration as derivatives of the class of piperazine-derived designer drugs, as well as alpha-pyr-rolidinopropiophenone (PPP), 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), 3', 4'-methylenedioxy-alpha-pyrrolidino-propiophenone (MDPPP), 4'-methyl-alpha-pyrrolidinopropiophenone (MPPP), and 4'-methyl-alpha-pyrrolidinoexanophenone (MPHP) as derivatives of the class of alpha-pyrrolidinophenone-derived designer drugs. Papers describing identification of in vivo or in vitro human or animal metabolites and cytochrome P450 isoenzyme dependent metabolism have been considered and summarized.

Versatile and on-demand biologics co-production in yeast.

Science.gov (United States)

Cao, Jicong; Perez-Pinera, Pablo; Lowenhaupt, Ky; Wu, Ming-Ru; Purcell, Oliver; de la Fuente-Nunez, Cesar; Lu, Timothy K

2018-01-08

Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment.

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality.

Science.gov (United States)

Içten, Elçin; Giridhar, Arun; Nagy, Zoltan K; Reklaitis, Gintaras V

2016-04-01

The features of a drop-on-demand-based system developed for the manufacture of melt-based pharmaceuticals have been previously reported. In this paper, a supervisory control system, which is designed to ensure reproducible production of high quality of melt-based solid oral dosages, is presented. This control system enables the production of individual dosage forms with the desired critical quality attributes: amount of active ingredient and drug morphology by monitoring and controlling critical process parameters, such as drop size and product and process temperatures. The effects of these process parameters on the final product quality are investigated, and the properties of the produced dosage forms characterized using various techniques, such as Raman spectroscopy, optical microscopy, and dissolution testing. A crystallization temperature control strategy, including controlled temperature cycles, is presented to tailor the crystallization behavior of drug deposits and to achieve consistent drug morphology. This control strategy can be used to achieve the desired bioavailability of the drug by mitigating variations in the dissolution profiles. The supervisor control strategy enables the application of the drop-on-demand system to the production of individualized dosage required for personalized drug regimens.

Exploring demand reduction through design, durability and 'usership' of fashion clothes.

Science.gov (United States)

Fletcher, Kate

2017-06-13

Global planetary boundaries confer limits to production and consumption of material goods. They also confer an obligation to experiment, as individuals and collectively as society, with less-materially-intensive, but no less exuberant, ways of living. This paper takes up this mantle and explores materials demand reduction through a focus on design, fashion garments and the universal, everyday activity of wearing clothes. It takes as its starting point the design of longer-lasting products, a widely favoured strategy for increasing materials efficiency and reducing materials demand in many sectors, including fashion. Drawing on scholarship in the field of design for sustainability and ethnographic research conducted in 16 locations in nine countries about already-existing practices of intensive use and maintenance of clothing, this paper critiques the effectiveness of durability strategies to reduce the amount of materials used. It argues for an update in the familiar preference within sustainability debates for the 'techno-fix' to explore instead resourceful use of materials as emerging from human actions and relationships with material goods. It suggests that, while facilitated by design, technology and engineering, opportunities to reduce materials demand begin in individual and collective practices, which, in turn, have dynamic implications for use of materials.This article is part of the themed issue 'Material demand reduction'. © 2017 The Author(s).

Drug plan design incentives among Medicare prescription drug plans.

Science.gov (United States)

Huskamp, Haiden A; Keating, Nancy L; Dalton, Jesse B; Chernew, Michael E; Newhouse, Joseph P

2014-07-01

Medicare Advantage prescription drug plans (MA-PDs) and standalone prescription drug plans (PDPs) face different incentives for plan design resulting from the scope of covered benefits (only outpatient drugs for PDPs versus all drug and nondrug services for Medicare Advantage [MA]/MA-PDs). The objective is to begin to explore how MA-PDs and PDPs may be responding to their different incentives related to benefit design. We compared 2012 PDP and MA-PD average formulary coverage, prior authorization (PA) or step therapy use, and copayment requirements for drugs in 6 classes used commonly among Medicare beneficiaries. We primarily used 2012 Prescription Drug Plan Formulary and Pharmacy Network Files and MA enrollment data. 2011 Truven Health MarketScan claims were used to estimate drug prices and to compute drug market share. Average coverage and PA/step rates, and average copayment requirements, were weighted by plan enrollment and drug market share. MA-PDs are generally more likely to cover and less likely to require PA/step for brand name drugs with generic alternatives than PDPs, and MA-PDs often have lower copayment requirements for these drugs. For brands without generics, we generally found no differences in average rates of coverage or PA/step, but MA-PDs were more likely to cover all brands without generics in a class. We found modest, confirmatory evidence suggesting that PDPs and MA-PDs respond to different incentives for plan design. Future research is needed to understand the factors that influence Medicare drug plan design decisions.

Nanocomposite Hydrogels: 3D Polymer-Nanoparticle Synergies for On-Demand Drug Delivery.

Science.gov (United States)

Merino, Sonia; Martín, Cristina; Kostarelos, Kostas; Prato, Maurizio; Vázquez, Ester

2015-05-26

Considerable progress in the synthesis and technology of hydrogels makes these materials attractive structures for designing controlled-release drug delivery systems. In particular, this review highlights the latest advances in nanocomposite hydrogels as drug delivery vehicles. The inclusion/incorporation of nanoparticles in three-dimensional polymeric structures is an innovative means for obtaining multicomponent systems with diverse functionality within a hybrid hydrogel network. Nanoparticle-hydrogel combinations add synergistic benefits to the new 3D structures. Nanogels as carriers for cancer therapy and injectable gels with improved self-healing properties have also been described as new nanocomposite systems.

Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

Science.gov (United States)

Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

2010-01-01

A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

Design and control of precision drop-on-demand herbicide application in agricultural robotics

OpenAIRE

Urdal, Frode; Utstumo, Trygve; Vatne, Jan Kåre; Ellingsen, Simen Andreas Ådnøy; Gravdahl, Jan Tommy

2014-01-01

This is the author’s final, accepted and refereed manuscript to the article. Drop-on-demand weed control is a field of research within Precision Agriculture, where the herbicide application is controlled down to individual droplets. This paper focuses on the fluid dynamics and electronics design of the droplet dispensing. The droplets are formed through an array of nozzles, controlled by two-way solenoid valves. A much used control circuit for opening and closing a soleno...

The role of water molecules in computational drug design.

Science.gov (United States)

de Beer, Stephanie B A; Vermeulen, Nico P E; Oostenbrink, Chris

2010-01-01

Although water molecules are small and only consist of two different atom types, they play various roles in cellular systems. This review discusses their influence on the binding process between biomacromolecular targets and small molecule ligands and how this influence can be modeled in computational drug design approaches. Both the structure and the thermodynamics of active site waters will be discussed as these influence the binding process significantly. Structurally conserved waters cannot always be determined experimentally and if observed, it is not clear if they will be replaced upon ligand binding, even if sufficient space is available. Methods to predict the presence of water in protein-ligand complexes will be reviewed. Subsequently, we will discuss methods to include water in computational drug research. Either as an additional factor in automated docking experiments, or explicitly in detailed molecular dynamics simulations, the effect of water on the quality of the simulations is significant, but not easily predicted. The most detailed calculations involve estimates of the free energy contribution of water molecules to protein-ligand complexes. These calculations are computationally demanding, but give insight in the versatility and importance of water in ligand binding.

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

Science.gov (United States)

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 PELE method within a few hours of simulation, positioning PELE as a tool applicable for rapid drug design cycles.

[Designer drugs in Jutland].

Science.gov (United States)

Simonsen, K W; Kaa, E

2001-04-16

The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs. All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined. MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly. MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

Core-shell designed scaffolds for drug delivery and tissue engineering.

Science.gov (United States)

Perez, Roman A; Kim, Hae-Won

2015-07-01

Scaffolds that secure and deliver therapeutic ingredients like signaling molecules and stem cells hold great promise for drug delivery and tissue engineering. Employing a core-shell design for scaffolds provides a promising solution. Some unique methods, such as co-concentric nozzle extrusion, microfluidics generation, and chemical confinement reactions, have been successful in producing core-shelled nano/microfibers and nano/microspheres. Signaling molecules and drugs, spatially allocated to the core and/or shell part, can be delivered in a controllable and sequential manner for optimal therapeutic effects. Stem cells can be loaded within the core part on-demand, safely protected from the environments, which ultimately affords ex vivo culture and in vivo tissue engineering. The encapsulated cells experience three-dimensional tissue-mimic microenvironments in which therapeutic molecules are secreted to the surrounding tissues through the semi-permeable shell. Tuning the material properties of the core and shell, changing the geometrical parameters, and shaping them into proper forms significantly influence the release behaviors of biomolecules and the fate of the cells. This topical issue highlights the immense usefulness of core-shell designs for the therapeutic actions of scaffolds in the delivery of signaling molecules and stem cells for tissue regeneration and disease treatment. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Homochiral drugs: a demanding tendency of the pharmaceutical industry.

Science.gov (United States)

Núñez, María C; García-Rubiño, M Eugenia; Conejo-García, Ana; Cruz-López, Olga; Kimatrai, María; Gallo, Miguel A; Espinosa, Antonio; Campos, Joaquín M

2009-01-01

The issue of drug chirality is now a major theme in the design and development of new drugs, underpinned by a new understanding of the role of molecular recognition in many pharmacologically relevant events. In general, three methods are utilized for the production of a chiral drug: the chiral pool, separation of racemates, and asymmetric synthesis. Although the use of chiral drugs predates modern medicine, only since the 1980's has there been a significant increase in the development of chiral pharmaceutical drugs. An important commercial reason is that as patents on racemic drugs expire, pharmaceutical companies have the opportunity to extend patent coverage through development of the chiral switch enantiomers with desired bioactivity. Stimulated by the new policy statements issued by the regulatory agencies, the pharmaceutical industry has systematically begun to develop chiral drugs in enantiometrically enriched pure forms. This new trend has caused a tremendous change in the industrial small- and large-scale production to enantiomerically pure drugs, leading to the revisiting and updating of old technologies, and to the development of new methodologies of their large-scale preparation (as the use of stereoselective syntheses and biocatalyzed reactions). The final decision whether a given chiral drug will be marketed in an enantiomerically pure form, or as a racemic mixture of both enantiomers, will be made weighing all the medical, financial and social proficiencies of one or other form. The kinetic, pharmacological and toxicological properties of individual enantiomers need to be characterized, independently of a final decision.

4D-QSAR: Perspectives in Drug Design

Directory of Open Access Journals (Sweden)

Carolina H. Andrade

2010-05-01

Full Text Available Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. The quantitative structure–activity relationship (QSAR formalisms are among the most important strategies that can be applied for the successful design new molecules. This review provides a comprehensive review on the evolution and current status of 4D-QSAR, highlighting present challenges and new opportunities in drug design.

Video-on-demand network design and maintenance using fuzzy optimization.

Science.gov (United States)

Abadpour, Arash; Alfa, Attahiru Sule; Diamond, Jeff

2008-04-01

Video-on-demand (VoD) is the entertainment source that, in the future, will likely overtake regular television in many aspects. Although many companies have deployed working VoD services, some aspects of the VoD should still undergo further improvement in order for it to reach to the foreseen potentials. An important aspect of a VoD system is the underlying network in which it operates. According to the huge number of customers in this network, it should be carefully designed to fulfill certain performance criteria. This process should be capable of finding optimal locations for the nodes of the network as well as determining the content that should be cached in each one. While this problem is categorized in the general group of network optimization problems, its specific characteristics demand a new solution to be sought for it. In this paper, which is inspired by the successful use of fuzzy optimization in similar problems in other fields, a fuzzy objective function that is heuristically shown to minimize the communication cost in a VoD network is derived while also controlling the storage cost. Then, an iterative algorithm is proposed to find a locally optimal solution to the proposed objective function. Capitalizing on the unrepeatable tendency of the proposed algorithm, a heuristic method for picking a good solution from a bundle of solutions produced by the proposed algorithm is also suggested. This paper includes a formal statement of the problem and its mathematical analysis. In addition, different scenarios in which the proposed algorithm can be utilized are discussed.

Designing cost effective water demand management programs in Australia.

Science.gov (United States)

White, S B; Fane, S A

2002-01-01

This paper describes recent experience with integrated resource planning (IRP) and the application of least cost planning (LCP) for the evaluation of demand management strategies in urban water. Two Australian case studies, Sydney and Northern New South Wales (NSW) are used in illustration. LCP can determine the most cost effective means of providing water services or alternatively the cheapest forms of water conservation. LCP contrasts to a traditional approach of evaluation which looks only at means of increasing supply. Detailed investigation of water usage, known as end-use analysis, is required for LCP. End-use analysis allows both rigorous demand forecasting, and the development and evaluation of conservation strategies. Strategies include education campaigns, increasing water use efficiency and promoting wastewater reuse or rainwater tanks. The optimal mix of conservation strategies and conventional capacity expansion is identified based on levelised unit cost. IRP uses LCP in the iterative process, evaluating and assessing options, investing in selected options, measuring the results, and then re-evaluating options. Key to this process is the design of cost effective demand management programs. IRP however includes a range of parameters beyond least economic cost in the planning process and program designs, including uncertainty, benefit partitioning and implementation considerations.

Computer Aided Drug Design: Success and Limitations.

Science.gov (United States)

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

2016-01-01

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

Pulse Check: Trends in Drug Abuse, Mid-Year 2000.

Science.gov (United States)

Meth, Marcia; Chalmers, Rebecca; Bassin, Gail

This report serves as a source of information on drug abuse and drug markets. It aims to describe drug-abusing populations; emerging drugs; new routes of administration; varying use patterns; changing demand for treatment; drug-related criminal activity; and shifts in supply and distribution patterns. It is not designed to be used as a law…

Smarter Drugs: How Protein Crystallography Revolutionizes Drug Design

International Nuclear Information System (INIS)

Smith, Clyde

2005-01-01

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.

Computer-Aided Drug Design in Epigenetics

Science.gov (United States)

Lu, Wenchao; Zhang, Rukang; Jiang, Hao; Zhang, Huimin; Luo, Cheng

2018-03-01

Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field.

Computer-Aided Drug Design in Epigenetics

Science.gov (United States)

Lu, Wenchao; Zhang, Rukang; Jiang, Hao; Zhang, Huimin; Luo, Cheng

2018-01-01

Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation, and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field. PMID:29594101

Individual and combined effects of cannabis and tobacco on drug reward processing in non-dependent users.

Science.gov (United States)

Hindocha, Chandni; Lawn, Will; Freeman, Tom P; Curran, H Valerie

2017-11-01

Cannabis and tobacco are often smoked simultaneously in joints, and this practice may increase the risks of developing tobacco and/or cannabis use disorders. Currently, there is no human experimental research on how these drugs interact on addiction-related measures. This study aimed to investigate how cannabis and tobacco, each alone and combined together in joints, affected individuals' demand for cannabis puffs and cigarettes, explicit liking of drug and non-drug-related stimuli and craving. A double-blind, 2 (active cannabis, placebo cannabis) × 2 (active tobacco, placebo tobacco) crossover design was used with 24 non-dependent cannabis and tobacco smokers. They completed a pleasantness rating task (PRT), a marijuana purchase task (MPT) and a cigarette purchase task (CPT) alongside measures of craving pre- and post-drug administration. Relative to placebo cannabis, active cannabis reduced liking of cannabis-associated stimuli and increased response time to all stimuli except cigarette-related stimuli. Relative to placebo cannabis, active cannabis decreased demand for cannabis puffs (trends for breakpoint and elasticity) and cigarettes (breakpoint, P max , O max ) on several characteristics of the purchase tasks. We found no evidence that active tobacco, both alone or combined with cannabis, had an effect on liking, demand or craving. Acutely, cannabis reduced liking of cannabis-related stimuli and demand for cannabis itself. Acute cannabis also reduced demand for cigarettes on the CPT. Acute tobacco administration did not affect demand or pleasantness ratings for cigarettes themselves or cannabis. In non-dependent cannabis and tobacco co-users, tobacco did not influence the rewarding effects of cannabis.

A very demanding spectrometer optical design for ExoMars Mission

Science.gov (United States)

Belenguer, T.; Fernandez-Rodriguez, M.; Colombo, M.; Diaz-Catalá, E.; Sanchez-Páramo, J.

2017-11-01

The objective of this report is to present the study performed for a specially demanding solution of a spectrometer [1] design based on a transmissive holographic grating especially designed to actuate as the dispersion element. The main driver of the design has been to obtain a device with a clear reduction in mass, power and mechanical envelope with respect to the previous configuration based on a prism and/or Echelle grating. This simplification is produced mainly at expense of the waveband range. This study has been carried out by Laboratorio de Instrumentación Espacial (LINES) optical designers from Instituto Nacional de Técnica Aeroespacial (INTA).

Computer-Aided Drug Design in Epigenetics

Directory of Open Access Journals (Sweden)

Wenchao Lu

2018-03-01

Full Text Available Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation, and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field.

Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

Science.gov (United States)

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.…

Design of an Implantable Device for Ocular Drug Delivery

Directory of Open Access Journals (Sweden)

Jae-Hwan Lee

2012-01-01

Full Text Available 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.

Knowledge acquisition and interface design for learning on demand systems

Science.gov (United States)

Nelson, Wayne A.

1993-01-01

The rapid changes in our world precipitated by technology have created new problems and new challenges for education and training. A knowledge 'explosion' is occurring as our society moves toward a service oriented economy that relies on information as the major resource. Complex computer systems are beginning to dominate the workplace, causing alarming growth and change in many fields. The rapidly changing nature of the workplace, especially in fields related to information technology, requires that our knowledge be updated constantly. This characteristic of modern society poses seemingly unsolvable instructional problems involving coverage and obsolescence. The sheer amount of information to be learned is rapidly increasing, while at the same time some information becomes obsolete in light of new information. Education, therefore, must become a lifelong process that features learning of new material and skills as needed in relation to the job to be done. Because of the problems cited above, the current model of learning in advance may no longer be feasible in our high-technology world. In many cases, learning in advance is impossible because there are simply too many things to learn. In addition, learning in advance can be time consuming, and often results in decontextualized knowledge that does not readily transfer to the work environment. The large and growing discrepancy between the amount of potentially relevant knowledge available and the amount a person can know and remember makes learning on demand an important alternative to current instructional practices. Learning on demand takes place whenever an individual must learn something new in order to perform a task or make a decision. Learning on demand is a promising approach for addressing the problems of coverage and obsolescence because learning is contextualized and integrated into the task environment rather than being relegated to a separate phase that precedes work. Learning on demand allows learners

Multiscale Modeling in the Clinic: Drug Design and Development

Energy Technology Data Exchange (ETDEWEB)

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

2016-02-17

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

Editorial: in silico drug design and medicinal chemistry).

Science.gov (United States)

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.

Drug design: Insights from atomistic simulations

International Nuclear Information System (INIS)

Collu, F.; Spiga, E.; Kumar, A.; Hajjar, E.; Vargiu, A.V.; Ceccarelli, M.; Ruggerone, P.

2009-01-01

Computer simulations have become a widely used and powerful tool to study the behaviour of many-particle and many-interaction systems and processes such as nucleic acid dynamics, drug-DNA interactions, enzymatic processes, membrane, antibiotics. The increased reliability of computational techniques has made possible to plane a bottom-up approach in drug design, i.e. designing molecules with improved properties starting from the knowledge of the molecular mechanisms. However, the in silico techniques have to face the fact that the number of degrees of freedom involved in biological systems is very large while the time scale of several biological processes is not accessible to standard simulations. Algorithms and methods have been developed and are still under construction to bridge these gaps. Here we review the activities of our group focussed on the time-scale bottleneck and, in particular, on the use of the meta dynamics scheme that allows the investigation of rare events in reasonable computer time without reducing the accuracy of the calculation. In particular, we have devoted particular attention to the characterization at microscopic level of translocation of antibiotics through membrane pores, aiming at the identification of structural and dynamical features helpful for a rational drug design.

Defining Patient Centric Pharmaceutical Drug Product Design.

Science.gov (United States)

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.

Thermodynamic Studies for Drug Design and Screening

Science.gov (United States)

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

Thermodynamic studies for drug design and screening.

Science.gov (United States)

Garbett, Nichola C; Chaires, Jonathan B

2012-04-01

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. 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. 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 toward 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 the design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. © 2012 Informa UK, Ltd.

Protein Crystallography: A 'Must' Technology for Drug Design

International Nuclear Information System (INIS)

Matsuzaki, Takao

2004-01-01

The history of drug-related protein crystallography and drug design is reviewed to show that 'Lead Generation' is high-lighted in the pharmaceutical industry nowadays. A new drug design method has been developed. The method gave very high success rate; 10-60 % gave < 100 μM, 90 % gave < 10 mM. The crystal structures of drug-protein complexes have become even more important to give solid experimental bases for e.g. 1,000 designed structures and to find the new mechanisms of drug action

Fabricate-On-Demand Vacuum Insulating Glazings

Energy Technology Data Exchange (ETDEWEB)

McCamy, James W. [PPG Industries, Inc., Pittsburgh, PA (United States)

2017-09-19

PPG proposed to design a fabricate-on-demand manufacturing process to overcome the cost and supply chain issues preventing widespread adoption of vacuum insulated glazing (VIG) units. To do so, we focused on improving three areas of VIG manufacturing that drive high costs and limit the ability for smaller manufacturers to enter the market: edge sealing, pillar design/placement, and evacuating the VIG.

The Design of Passive Optical Networking+Ethernet over Coaxial Cable Access Networking and Video-on-Demand Services Carrying

Science.gov (United States)

Ji, Wei

2013-07-01

Video on demand is a very attractive service used for entertainment, education, and other purposes. The design of passive optical networking+Ethernet over coaxial cable accessing and a home gateway system is proposed. The network integrates the passive optical networking and Ethernet over coaxial cable to provide high dedicated bandwidth for the metropolitan video-on-demand services. Using digital video broadcasting, IP television protocol, unicasting, and broadcasting mechanisms maximizes the system throughput. The home gateway finishes radio frequency signal receiving and provides three kinds of interfaces for high-definition video, voice, and data, which achieves triple-play and wire/wireless access synchronously.

An Opportunistic Wireless Charging System Design for an On-Demand Shuttle Service: Preprint

Energy Technology Data Exchange (ETDEWEB)

Doubleday, Kate; Meintz, Andrew; Markel, Tony

2016-08-01

System right-sizing is critical to implementation of in-motion wireless power transfer (WPT) for electric vehicles. This study introduces a modeling tool, WPTSim, which uses one-second speed, location, and road grade data from an on-demand employee shuttle in operation to simulate the incorporation of WPT at fine granularity. Vehicle power and state of charge are simulated over the drive cycle to evaluate potential system designs. The required battery capacity is determined based on the rated power at a variable number of charging locations. Adding just one WPT location can more than halve the battery capacity needed. Many configurations are capable of being self sustaining with WPT, while others benefit from supplemental stationary charging.

Drug delivery across length scales.

Science.gov (United States)

Delcassian, Derfogail; Patel, Asha K; Cortinas, Abel B; Langer, Robert

2018-02-20

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

In silico fragment-based drug design.

Science.gov (United States)

Konteatis, Zenon D

2010-11-01

In silico fragment-based drug design (FBDD) is a relatively new approach inspired by the success of the biophysical fragment-based drug discovery field. Here, we review the progress made by this approach in the last decade and showcase how it complements and expands the capabilities of biophysical FBDD and structure-based drug design to generate diverse, efficient drug candidates. Advancements in several areas of research that have enabled the development of in silico FBDD and some applications in drug discovery projects are reviewed. The reader is introduced to various computational methods that are used for in silico FBDD, the fragment library composition for this technique, special applications used to identify binding sites on the surface of proteins and how to assess the druggability of these sites. In addition, the reader will gain insight into the proper application of this approach from examples of successful programs. In silico FBDD captures a much larger chemical space than high-throughput screening and biophysical FBDD increasing the probability of developing more diverse, patentable and efficient molecules that can become oral drugs. The application of in silico FBDD holds great promise for historically challenging targets such as protein-protein interactions. Future advances in force fields, scoring functions and automated methods for determining synthetic accessibility will all aid in delivering more successes with in silico FBDD.

Drug Design and Emotion

Science.gov (United States)

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.

Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

Science.gov (United States)

Stegemann, Sven

2018-06-01

The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

21 CFR 516.29 - Termination of MUMS-drug designation.

Science.gov (United States)

2010-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.29 Termination of MUMS-drug designation. (a... exclusive marketing rights under this subpart. (d) FDA may terminate designation if it independently...

Market Design for Rapid Demand Response - The Case of Kenya

OpenAIRE

Kurt Nielsen; Tseganesh Wubale Tamirat

2014-01-01

We suggest a market design for rapid demand response in electricity markets. The solution consists of remotely controlled switches, meters, forecasting models as well as a flexible auction market to set prices and select endusers job by job. The auction market motivates truth-telling and makes it simple to involve the endusers in advance and to activate demand response immediately. The collective solution is analyzed and economic simulations are conducted for the case of Kenya. Kenya has been...

Demand-Based Optimal Design of Storage Tank with Inerter System

Directory of Open Access Journals (Sweden)

Shiming Zhang

2017-01-01

Full Text Available A parameter optimal design method for a tank with an inerter system is proposed in this study based on the requirements of tank vibration control to improve the effectiveness and efficiency of vibration control. Moreover, a response indicator and a cost control indicator are selected based on the control targets for liquid storage tanks for simultaneously minimizing the dynamic response and controlling costs. These indicators are reformulated through a random vibration analysis under virtual excitation. The problem is then transformed from a multiobjective optimization problem to a single-objective nonlinear problem using the ε-constraint method, which is consistent with the demand-based method. White noise excitation can be used to design the tank with the inerter system under seismic excitation to simplify the calculation. Subsequently, a MATLAB-based calculation program is compiled, and several optimization cases are examined under different excitation conditions. The effectiveness of the demand-based method is proven through a time history analysis. The results show that specific vibration control requirements can be met at the lowest cost with a simultaneous reduction in base shears and overturning base moments.

Designer Drugs: A Review of Literature Abdulsallam Bakdash

Directory of Open Access Journals (Sweden)

Abdulsallam Bakdash

2015-05-01

Full Text Available A new phenomenon in the drug market has appeared in recent years: there has been an increase in the number and types of designer drugs. A massive influx of these structural and/or functional analogs of controlled substances has resulted in an increase in their marketing and abuse. At present, these drugs are significantly more widely available compared to previous years because they are relatively inexpensive and marketed as being safer than classic drugs of abuse. The most important factor in the spread of designer drugs is that the majority of these substances are undetectable as drugs or illegal drugs in standard drug testing procedures. The biological effects of these substances are largely unknown to both users and medical scientists. However, most known cases of abuse have shown serious and dangerous physical and psychological reactions in users. The manufacturing and marketing of designer drugs presents a major challenge for specialist sectors, especially laboratories that have to test these substances. This highlights the important role of drugcontrol institutions and regulatory and legislative bodies to determine the legal status of these drugs, which are designed and marketed - mostly through the internet - as being legal. All of these factors make it incumbent upon these sectors to form a unified goal and strategy to control these substances and prevent their spread. This review provides fundamental information about designer drugs. This will provide an accurate overview of their status, and will aid future work to develop a regulatory and legislative strategy to combat their manufacture, marketing, and use.

Demand curves for hypothetical cocaine in cocaine-dependent individuals.

Science.gov (United States)

Bruner, Natalie R; Johnson, Matthew W

2014-03-01

Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

Optimal transport on supply-demand networks.

Science.gov (United States)

Chen, Yu-Han; Wang, Bing-Hong; Zhao, Li-Chao; Zhou, Changsong; Zhou, Tao

2010-06-01

In the literature, transport networks are usually treated as homogeneous networks, that is, every node has the same function, simultaneously providing and requiring resources. However, some real networks, such as power grids and supply chain networks, show a far different scenario in which nodes are classified into two categories: supply nodes provide some kinds of services, while demand nodes require them. In this paper, we propose a general transport model for these supply-demand networks, associated with a criterion to quantify their transport capacities. In a supply-demand network with heterogeneous degree distribution, its transport capacity strongly depends on the locations of supply nodes. We therefore design a simulated annealing algorithm to find the near optimal configuration of supply nodes, which remarkably enhances the transport capacity compared with a random configuration and outperforms the degree target algorithm, the betweenness target algorithm, and the greedy method. This work provides a start point for systematically analyzing and optimizing transport dynamics on supply-demand networks.

Evaluate the interactive and reusable service in adaptive on demand applications

OpenAIRE

Hwang , Chyi-Wen

2007-01-01

In this paper, the researcher based on the open platforms and tools for personalized learning idea, with the “ Interactive & reusable” function in UI design model, directly dealing with Knowledge on demand (KOD) service from the aspect-oriented and object-oriented issue. Moreover, to propose the KOD combine with VOD (Video on Demand); AOD (Audio on Demand); COD (Course on Demand) and IOD (Information on Demand in Global index searching) in diversity of hypermedia metadata.

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

Science.gov (United States)

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.

A Nondominated Genetic Algorithm Procedure for Multiobjective Discrete Network Design under Demand Uncertainty

Directory of Open Access Journals (Sweden)

Bian Changzhi

2015-01-01

Full Text Available This paper addresses the multiobjective discrete network design problem under demand uncertainty. The OD travel demands are supposed to be random variables with the given probability distribution. The problem is formulated as a bilevel stochastic optimization model where the decision maker’s objective is to minimize the construction cost, the expectation, and the standard deviation of total travel time simultaneously and the user’s route choice is described using user equilibrium model on the improved network under all scenarios of uncertain demand. The proposed model generates globally near-optimal Pareto solutions for network configurations based on the Monte Carlo simulation and nondominated sorting genetic algorithms II. Numerical experiments implemented on Nguyen-Dupuis test network show trade-offs among construction cost, the expectation, and standard deviation of total travel time under uncertainty are obvious. Investment on transportation facilities is an efficient method to improve the network performance and reduce risk under demand uncertainty, but it has an obvious marginal decreasing effect.

A Nondominated Genetic Algorithm Procedure for Multiobjective Discrete Network Design under Demand Uncertainty

OpenAIRE

Changzhi, Bian

2015-01-01

This paper addresses the multiobjective discrete network design problem under demand uncertainty. The OD travel demands are supposed to be random variables with the given probability distribution. The problem is formulated as a bilevel stochastic optimization model where the decision maker’s objective is to minimize the construction cost, the expectation, and the standard deviation of total travel time simultaneously and the user’s route choice is described using user equilibrium model on the...

Smart Demand Response Based on Smart Homes

Directory of Open Access Journals (Sweden)

Jingang Lai

2015-01-01

Full Text Available Smart homes (SHs are crucial parts for demand response management (DRM of smart grid (SG. The aim of SHs based demand response (DR is to provide a flexible two-way energy feedback whilst (or shortly after the consumption occurs. It can potentially persuade end-users to achieve energy saving and cooperate with the electricity producer or supplier to maintain balance between the electricity supply and demand through the method of peak shaving and valley filling. However, existing solutions are challenged by the lack of consideration between the wide application of fiber power cable to the home (FPCTTH and related users’ behaviors. Based on the new network infrastructure, the design and development of smart DR systems based on SHs are related with not only functionalities as security, convenience, and comfort, but also energy savings. A new multirouting protocol based on Kruskal’s algorithm is designed for the reliability and safety of the SHs distribution network. The benefits of FPCTTH-based SHs are summarized at the end of the paper.

Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

Directory of Open Access Journals (Sweden)

Martina Nardoni

2018-03-01

Full Text Available Recently, magnetic nanoparticles (MNPs have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF, which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs, they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

Science.gov (United States)

Nardoni, Martina; Della Valle, Elena; Liberti, Micaela; Relucenti, Michela; Casadei, Maria Antonietta; Paolicelli, Patrizia; Apollonio, Francesca; Petralito, Stefania

2018-03-27

Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

Efficacy of a Targeted Drug Delivery on-Demand Bolus Option for Chronic Pain.

Science.gov (United States)

Bolash, Robert B; Niazi, Tariq; Kumari, Meera; Azer, Gerges; Mekhail, Nagy

2018-03-01

Intrathecal targeted drug delivery systems historically required physician office visits for dose adjustment to manage fluctuating pain. A wireless device now enables patients to supplement their basal intrathecal infusion with a programmed on-demand bolus dose. We sought to quantify the change in oral breakthrough opioid need associated with the use of an intrathecal bolus in comparison to those treated with the basal infusion alone. Demographic, dosage, bolus usage and longevity data were extracted from the historical medical record of 69 patients (18/51 bolus/nonbolus) followed continuously at our center. Medication consumption and Pain Disability Index measures were obtained at baseline and most recent follow-up. Among patients with the bolus option, only 2 (11%; confidence interval [CI] 0% to 26%) continued to require oral opiates to manage breakthrough pain compared to 29 (57%; CI 43% to 71%) without the bolus option. The Pain Disability Index score decreased by 19% in patients with the bolus option and by 25% in those with the basal infusion. Total daily intrathecal opioid intake was 34% lower in the group with the bolus device. Utilizing an intrathecal bolus to treat incident pain was a safe way to manage unpredictable breakthrough pain and may represent a cost-saving opportunity by eliminating the need for oral analgesic medications. © 2017 World Institute of Pain.

75 FR 8968 - Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability

Science.gov (United States)

2010-02-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0090] Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability... familiar and less familiar approaches. As more experience is obtained with the less familiar designs...

Design of limited-stop service based on the degree of unbalance of passenger demand

Science.gov (United States)

2018-01-01

This paper presents a limited-stop service for a bus fleet to meet the unbalanced demand of passengers on a bus route and to improve the transit service of the bus route. This strategy includes two parts: a degree assessment of unbalanced passenger demand and an optimization of the limited-stop service. The degree assessment of unbalanced passenger demand, which is based on the different passenger demand between stations and the unbalance of passengers within the station, is used to judge whether implementing the limited-stop service is necessary for a bus route. The optimization of limited-stop service considers the influence of stop skipping action and bus capacity on the left-over passengers to determine the proper skipping stations for the bus fleet serving the entire route by minimizing both the waiting time and in-vehicle time of passengers and the running time of vehicles. A solution algorithm based on genetic algorithm is also presented to evaluate the degree of unbalanced passenger demand and optimize the limited-stop scheme. Then, the proper strategy is tested on a bus route in Changchun city of China. The threshold of degree assessment of unbalanced passenger demand can be calibrated and adapted to different passenger demands. PMID:29505585

Design of limited-stop service based on the degree of unbalance of passenger demand.

Science.gov (United States)

Zhang, Hu; Zhao, Shuzhi; Liu, Huasheng; Liang, Shidong

2018-01-01

This paper presents a limited-stop service for a bus fleet to meet the unbalanced demand of passengers on a bus route and to improve the transit service of the bus route. This strategy includes two parts: a degree assessment of unbalanced passenger demand and an optimization of the limited-stop service. The degree assessment of unbalanced passenger demand, which is based on the different passenger demand between stations and the unbalance of passengers within the station, is used to judge whether implementing the limited-stop service is necessary for a bus route. The optimization of limited-stop service considers the influence of stop skipping action and bus capacity on the left-over passengers to determine the proper skipping stations for the bus fleet serving the entire route by minimizing both the waiting time and in-vehicle time of passengers and the running time of vehicles. A solution algorithm based on genetic algorithm is also presented to evaluate the degree of unbalanced passenger demand and optimize the limited-stop scheme. Then, the proper strategy is tested on a bus route in Changchun city of China. The threshold of degree assessment of unbalanced passenger demand can be calibrated and adapted to different passenger demands.

Study on optimization design of superconducting magnet for magnetic force assisted drug delivery system

International Nuclear Information System (INIS)

Fukui, S.; Abe, R.; Ogawa, J.; Oka, T.; Yamaguchi, M.; Sato, T.; Imaizumi, H.

2007-01-01

Analytical study on the design of the superconducting magnet for the magnetic force assisted drug delivery system is presented in this paper. The necessary magnetic field condition to reside the magnetic drug particle in the blood vessels is determined by analyzing the particle motion in the blood vessel. The design procedure of the superconducting magnet for the M-DDS is presented and some case studies are conducted. The analytical results show that the superconducting magnet to satisfy the magnetic field conduction for the M-DDS is practically feasible

[Therapeutic drug monitoring of three antiepileptic drugs - Back on twenty years of experience].

Science.gov (United States)

Serragui, Samira; Zalagh, Fatima; Tanani, Driss Soussi; Ouammi, Lahcen; Moussa, Latifa Ait; Badrane, Narjis; Bencheikh, Rachida Soulaymani

2016-01-01

The therapeutic drug monitoring (TDM) of antiepileptic drugs is a tool widely used in the management of epilepsy. In Morocco, this monitoring is carried out by the Centre Anti Poison et Pharmacovigilance (CAPM) since April 1995. This is a retrospective study spanning 20 years. It concerns the therapeutic drug monitoring of Phenobarbital (PB) of carbamazepine (CBZ) and valproic acid (VPA). Therapeutic drug monitoring of the 3 antiepileptic drugs represent 58.85% of all applications received by the CAPM. The dosage of PB was ranked first followed by that of CBZ and finally by the VPA. Weak demand for therapeutic drug monitoring in Morocco could be explained by the low number of neurologists in addition to social factors. With its affordable price by patients, PB is the most prescribed antiepileptic drug in our country, which explains the high demand for its dosage. As for the therapeutic drug monitoring of the antiepileptic drug, they were mainly related to age, the occurrence of adverse effects, the association antiepileptic drugs or in the case of verification of patient compliance. Efforts are required for promoting the interests of therapeutic drug monitoring of antiepileptic drug in the management of epilepsy in Morocco.

Near-infrared induced release for localized on-demand drug delivery

NARCIS (Netherlands)

Vertommen, M.A.M.E.

2009-01-01

By non-invasive external triggering of drug release from an implant, pulsewise administration can be realized according to the patient’s needs and at specific locations in the human body. In comparison to more traditional delivery forms (e.g. oral or by injection), externally triggered drug release

On-Demand Special Use Airspace, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — We design and develope a Decision Support Tool (DST) that supports On-Demand Special Use Airspace (SUA) scheduling and flight plan optimization around SUA between...

On-Demand Special Use Airspace, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — We design and develop a Decision Support Tool (DST) that supports On-Demand Special Use Airspace (SUA) scheduling and flight plan optimization around SUA between...

[The use of saliva for exposure assessments on designer drugs among adolescents].

Science.gov (United States)

Napierała, Marta; Tezyk, Artur; Piznal, Małgorzata; Bogusiewicz, Joanna; Florek, Ewa

2015-01-01

Drug use is one of the fundamental problems of the contemporary world. Due to the debilitating effects on physical and mental health and the possibility of impaired social functions, it is extremely important to assess exposure to psychoactive substances among high-risk groups. Taking into account characteristics of adolescence, one of them includes young people. To assess the exposure of young people to drugs, survey research is the most commonly use. To establish reliability of the information indicated by the students, toxicological studies could be a good manner. High-performance liquid chromatography coupled with mass spectrometry (LC-MS) is currently one of the most common techniques use for the detection and determination of psychoactive substances in biological material. In practice, an important issue in toxicological studies is the selection of a suitable biological material. Taking into account economic considerations and the method of sampling, the saliva is an increasingly used alternative material. The aim of this study was to assess the exposure of junior high school students on psychoactive substances--designer drugs, through the analysis of surveys and qualitative analysis of saliva taken from teenagers. It has been shown that surveys are a relatively quick and easy form of assessing the exposure of young people to psychoactive substances, but require verification through toxicological analysis of biological material for the presence of psychoactive substances for their reliability. Poznan secondary school students experimented with designer drugs at a similar level as respondents of nationwide survey from 2013.

Computer aided drug design

Science.gov (United States)

Jain, A.

2017-08-01

Computer based method can help in discovery of leads and can potentially eliminate chemical synthesis and screening of many irrelevant compounds, and in this way, it save time as well as cost. Molecular modeling systems are powerful tools for building, visualizing, analyzing and storing models of complex molecular structure that can help to interpretate structure activity relationship. The use of various techniques of molecular mechanics and dynamics and software in Computer aided drug design along with statistics analysis is powerful tool for the medicinal chemistry to synthesis therapeutic and effective drugs with minimum side effect.

Modeling chemical reactions for drug design.

Science.gov (United States)

Gasteiger, Johann

2007-01-01

Chemical reactions are involved at many stages of the drug design process. This starts with the analysis of biochemical pathways that are controlled by enzymes that might be downregulated in certain diseases. In the lead discovery and lead optimization process compounds have to be synthesized in order to test them for their biological activity. And finally, the metabolism of a drug has to be established. A better understanding of chemical reactions could strongly help in making the drug design process more efficient. We have developed methods for quantifying the concepts an organic chemist is using in rationalizing reaction mechanisms. These methods allow a comprehensive modeling of chemical reactivity and thus are applicable to a wide variety of chemical reactions, from gas phase reactions to biochemical pathways. They are empirical in nature and therefore allow the rapid processing of large sets of structures and reactions. We will show here how methods have been developed for the prediction of acidity values and of the regioselectivity in organic reactions, for designing the synthesis of organic molecules and of combinatorial libraries, and for furthering our understanding of enzyme-catalyzed reactions and of the metabolism of drugs.

Demand Elasticity on the Transport Market

OpenAIRE

Teodor Perić; Nada Štrumberger

2002-01-01

The elasticity of demand for traffic se1vices is the adaptationof traffic supply to traffic demand. The elasticity of suchdemand is low which is specific of the transport market, especiallyfrom the aspect of designing traffic demand.The essence of the problem of low elasticity can be noticedin three basic properties:First, in the change of place which determines the traffic demandor traffic relation.Second is the continuity of the need to transport goods andpassengers.Third, the needs for tra...

A multifunctional multimaterial system for on-demand protein release.

Science.gov (United States)

Tuncaboylu, Deniz Ceylan; Friess, Fabian; Wischke, Christian; Lendlein, Andreas

2018-06-15

In order to provide best control of the regeneration process for each individual patient, the release of protein drugs administered during surgery may need to be timely adapted and/or delayed according to the progress of healing/regeneration. This study aims to establish a multifunctional implant system for a local on-demand release, which is applicable for various types of proteins. It was hypothesized that a tubular multimaterial container kit, which hosts the protein of interest as a solution or gel formulation, would enable on-demand release if equipped with the capacity of diameter reduction upon external stimulation. Using devices from poly(ɛ-caprolactone) networks, it could be demonstrated that a shape-memory effect activated by heat or NIR light enabled on-demand tube shrinkage. The decrease of diameter of these shape-memory tubes (SMT) allowed expelling the payload as demonstrated for several proteins including SDF-1α, a therapeutically relevant chemotactic protein, to achieve e.g. continuous release with a triggered add-on dosing (open tube) or an on-demand onset of bolus or sustained release (sealed tube). Considering the clinical relevance of protein factors in (stem) cell attraction to lesions and the progress in monitoring biomarkers in body fluids, such on-demand release systems may be further explored e.g. in heart, nerve, or bone regeneration in the future. Copyright © 2018. Published by Elsevier B.V.

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

Science.gov (United States)

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.

Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

Directory of Open Access Journals (Sweden)

Avinaba Mukherjee

2016-03-01

Full Text Available 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

Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.

Science.gov (United States)

Bian, Yuemin; Xie, Xiang-Qun Sean

2018-04-09

Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

Target based drug design - a reality in virtual sphere.

Science.gov (United States)

Verma, Saroj; Prabhakar, Yenamandra S

2015-01-01

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

Demand Response Within Current Electricity Wholesale Market Design

OpenAIRE

Ramos Gutierrez, Ariana Isabel; De Jonghe, Cedric; Six, Daan; Belmans, Ronnie

2013-01-01

The introduction of intermittent energy resources calls for the ability to modulate consumption patterns according to electricity availability. This paper provides a brief overview of the main electricity market design characteristics and places demand response within the framework of the existing timeline of market operation. The main differences between electricity markets lie in the price formation mechanisms where some markets pay-as- cleared and some pay- as- bid for the electricity tran...

[Designer drugs and caffeine - characteristics of psychoactive substances and their impact on the organism].

Science.gov (United States)

Wierzejska, Regina

2014-01-01

For many teenagers the time of growing up is a period of trying prohibited substances. Nowadays apart from alcohol and tobacco new designed, psychoactive substances known as "smart drugs" or "legal highs" are available. Intensive development of their market is taking place in the last few years which is difficult to overcome by regulations only. Toxicological tests used now are not able to detect the presence of many such substances in the body. Designer drugs cause the interest of young people even from small towns and many times taking them give effects requiring medical help. Caffeine is also a psychoactive substance but depending on the dose it can have positive or detrimental effect. Recently there are more and more products with caffeine, especially drinks and dietary supplements, what can cause the increase of consumption of caffeine. Children are particularly exposed to the adverse effect of high consumption of caffeine because of their small body weight and development of the central nervous system. This article presents actual data about the market of designer drugs, frequency of using them, consumption of caffeine by children and teenagers and about the impact of these substances on the organism.

Physics and Its Interfaces with Medicinal Chemistry and Drug Design

Science.gov (United States)

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.

Effects of mental demands during dispensing on perceived medication safety and employee well-being: a study of workload in pediatric hospital pharmacies.

Science.gov (United States)

Holden, Richard J; Patel, Neal R; Scanlon, Matthew C; Shalaby, Theresa M; Arnold, Judi M; Karsh, Ben-Tzion

2010-12-01

Pharmacy workload is a modifiable work system factor believed to affect both medication safety outcomes and employee outcomes, such as job satisfaction. This study sought to measure the effect of workload on safety and employee outcomes in 2 pediatric hospitals and to do so using a novel approach to pharmacy workload measurement. Rather than measuring prescription volume or other similar indicators, this study measured the type and intensity of mental demands experienced during the medication dispensing tasks. The effects of external (interruptions, divided attention, and rushing) and internal (concentration and effort) task demands on perceived medication error likelihood, adverse drug event likelihood, job dissatisfaction, and burnout were statistically estimated using multiple linear and logistic regression. Pharmacists and pharmacy technicians reported high levels of external and internal mental demands during dispensing. The study supported the hypothesis that external demands (interruptions, divided attention, and rushing) negatively impacted medication safety and employee well-being outcomes. However, as hypothesized, increasing levels of internal demands (concentration and effort) were not associated with greater perceived likelihood of error, adverse drug events, or burnout and even had a positive effect on job satisfaction. Replicating a prior study in nursing, this study shows that new conceptualizations and measures of workload can generate important new findings about both detrimental and beneficial effects of workload on patient safety and employee well-being. This study discusses what those findings imply for policy, management, and design concerning automation, cognition, and staffing. Copyright © 2010 Elsevier Inc. All rights reserved.

Effects of mental demands during dispensing on perceived medication safety and employee well being: A study of workload in pediatric hospital pharmacies

Science.gov (United States)

Holden, Richard J.; Patel, Neal R.; Scanlon, Matthew C.; Shalaby, Theresa M.; Arnold, Judi M.; Karsh, Ben-Tzion

2009-01-01

Background Pharmacy workload is a modifiable work system factor believed to affect both medication safety outcomes and employee outcomes such as job satisfaction. Objectives This study sought to measure the effect of workload on safety and employee outcomes in two pediatric hospitals and to do so using a novel approach to pharmacy workload measurement. Methods Rather than measuring prescription volume or other similar indicators, this study measured the type and intensity of mental demands experienced during the medication dispensing tasks. The effects of external (interruptions, divided attention, rushing) and internal (concentration, effort) task demands on perceived medication error likelihood, adverse drug event likelihood, job dissatisfaction, and burnout were statistically estimated using multiple linear and logistic regression. Results Pharmacists and pharmacy technicians reported high levels of external and internal mental demands during dispensing. The study supported the hypothesis that external demands (interruptions, divided attention, rushing) negatively impacted medication safety and employee well being outcomes. However, as hypothesized, increasing levels of internal demands (concentration and effort) were not associated with greater perceived likelihood of error, adverse drug events, or burnout, and even had a positive effect on job satisfaction. Conclusion Replicating a prior study in nursing, this study shows that new conceptualizations and measures of workload can generate important new findings about both detrimental and beneficial effects of workload on patient safety and employee well being. This study discusses what those findings imply for policy, management, and design concerning automation, cognition, and staffing. PMID:21111387

Generative Recurrent Networks for De Novo Drug Design.

Science.gov (United States)

Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

2018-01-01

Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Targeted proteins for diabetes drug design

Science.gov (United States)

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.

Targeted proteins for diabetes drug design

International Nuclear Information System (INIS)

Trang Nguyen, Ngoc Doan; Le, Ly Thi

2012-01-01

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. (review)

Flexible work designs and employee well-being: examining the effects of resources and demands

OpenAIRE

ter Hoeven, C.L.; van Zoonen, W.

2015-01-01

Advances in communication technology continue to expand the possibilities for redesigning work environments to allow for temporal and spatial flexibility. Although flexible work designs (FWDs) are typically launched with high expectations, recent research shows that FWDs also pose challenges to employees and can even impede employee well-being. Based on the Job Demands-Resources model, we argue that FWDs offer both advantages (FWD-related resources) and challenges (FWD-related demands) to emp...

Computer-aided drug design at Boehringer Ingelheim

Science.gov (United States)

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

2017-03-01

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

The Impact of Breakthrough Therapy Designation on Development Strategies and Timelines for Nononcology Drugs and Vaccines.

Science.gov (United States)

Poirier, A F; Murphy, W R

2016-12-01

The US Food and Drug Administration (FDA) Safety and Innovation Act (FDASIA, 2012) introduced the Breakthrough Therapy Designation (BTD), a new tool to expedite development of medicines to treat serious or life-threatening diseases. The majority of BTDs have gone to oncology drugs, and a recent publication by Shea et al. 1 reviewed the impact of BTD on oncology drug development. This article reviews the impact of BTD on development strategies and timelines for nononcology drugs. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Organic carbamates in drug design and medicinal chemistry.

Science.gov (United States)

Ghosh, Arun K; Brindisi, Margherita

2015-04-09

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

Drug design based on x-ray diffraction and steered molecular dynamics

Czech Academy of Sciences Publication Activity Database

Hašek, Jindřich; Skálová, Tereza; Dohnálek, Jan; Dušková, Jarmila; Petroková, Hana; Vondráčková, Eva; Zimmermann, K.

2005-01-01

Roč. 12, č. 3 (2005), s. 208-210 ISSN 1211-5894. [VUFB Conference on Modern Methods in Synthesis and Analysis of Active Pharmaceutical Substances /5./. Praha, 23.11.2005-24.11.2005] R&D Projects: GA AV ČR KJB4050312 Institutional research plan: CEZ:AV0Z40500505 Keywords : drug design * X-ray diffraction * steered molecular dynamics Subject RIV: CF - Physical ; Theoretical Chemistry

Design implications of incorporating employee profiles and workplace activity levels in travel demand management led parking demand assessments

CSIR Research Space (South Africa)

Letebele, MO

2008-07-01

Full Text Available spaces when the demand for parking is ever increasing. A more fundamental question, however, is how to better understand travel behaviour to enable the design of sustainable transport services, of which parking form part, in line with policy instruments...

Intratumor heterogeneity alters most effective drugs in designed combinations.

Science.gov (United States)

Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A

2014-07-22

The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.

e-Drug3D: 3D structure collections dedicated to drug repurposing and fragment-based drug design.

Science.gov (United States)

Pihan, Emilie; Colliandre, Lionel; Guichou, Jean-François; Douguet, Dominique

2012-06-01

In the drug discovery field, new uses for old drugs, selective optimization of side activities and fragment-based drug design (FBDD) have proved to be successful alternatives to high-throughput screening. e-Drug3D is a database of 3D chemical structures of drugs that provides several collections of ready-to-screen SD files of drugs and commercial drug fragments. They are natural inputs in studies dedicated to drug repurposing and FBDD. e-Drug3D collections are freely available at http://chemoinfo.ipmc.cnrs.fr/e-drug3d.html either for download or for direct in silico web-based screenings.

Demand Elasticity on the Transport Market

Directory of Open Access Journals (Sweden)

Teodor Perić

2002-09-01

Full Text Available The elasticity of demand for traffic se1vices is the adaptationof traffic supply to traffic demand. The elasticity of suchdemand is low which is specific of the transport market, especiallyfrom the aspect of designing traffic demand.The essence of the problem of low elasticity can be noticedin three basic properties:First, in the change of place which determines the traffic demandor traffic relation.Second is the continuity of the need to transport goods andpassengers.Third, the needs for transport may vmy according to thechanges in society and economy, and they also change thesources of traffic demand. Therefore, the elasticity of demandfor traffic se1vices is relatively low.

A Simulation of Rainwater Harvesting Design and Demand-Side Controls for Large Hospitals

Directory of Open Access Journals (Sweden)

Lawrence V. Fulton

2018-05-01

Full Text Available Inpatient health buildings in the United States are the most intensive users of water among large commercial buildings. Large facilities (greater than 1 million square feet consume an average of 90 million gallons per building per year. The distribution and treatment of water imposes a significant electrical power demand, which may be the single largest energy requirement for various states. Supply and demand-side solutions are needed, particularly in arid and semi-arid regions where water is scarce. This study uses continuous simulations based on 71 years of historical data to estimate how rainwater harvesting systems and demand-side interventions (e.g., low-flow devices, xeriscaping would offset the demand for externally-provided water sources in a semi-arid region. Simulations from time series models are used to generate alternative rainfall models to account for potential non-stationarity and volatility. Results demonstrate that hospital external water consumption might be reduced by approximately 25% using conservative assumptions and depending on the design of experiment parameters associated with rainfall capture area, building size, holding tank specifications, and conservation efforts.

Reforming private drug coverage in Canada: inefficient drug benefit design and the barriers to change in unionized settings.

Science.gov (United States)

O'Brady, Sean; Gagnon, Marc-André; Cassels, Alan

2015-02-01

Prescription drugs are the highest single cost component for employees' benefits packages in Canada. While industry literature considers cost-containment for prescription drug costs to be a priority for insurers and employers, the implementation of cost-containment measures for private drug plans in Canada remains more of a myth than a reality. Through 18 semi-structured phone interviews conducted with experts from private sector companies, unions, insurers and plan advisors, this study explores the reasons behind this incapacity to implement cost-containment measures by examining how private sector employers negotiate drug benefit design in unionized settings. Respondents were asked questions on how employee benefits are negotiated; the relationships between the players who influence drug benefit design; the role of these players' strategies in influencing plan design; the broad system that underpins drug benefit design; and the potential for a universal pharmacare program in Canada. The study shows that there is consensus about the need to educate employees and employers, more collaboration and data-sharing between these two sets of players, and for external intervention from government to help transform established norms in terms of private drug plan design. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Optimization Design Method and Experimental Validation of a Solar PVT Cogeneration System Based on Building Energy Demand

Directory of Open Access Journals (Sweden)

Chao Zhou

2017-08-01

Full Text Available Photovoltaic-thermal (PVT technology refers to the integration of a photovoltaic (PV and a conventional solar thermal collector, representing the deep exploitation and utilization of solar energy. In this paper, we evaluate the performance of a solar PVT cogeneration system based on specific building energy demand using theoretical modeling and experimental study. Through calculation and simulation, the dynamic heating load and electricity load is obtained as the basis of the system design. An analytical expression for the connection of PVT collector array is derived by using basic energy balance equations and thermal models. Based on analytical results, an optimized design method was carried out for the system. In addition, the fuzzy control method of frequency conversion circulating water pumps and pipeline switching by electromagnetic valves is introduced in this paper to maintain the system at an optimal working point. Meanwhile, an experimental setup is established, which includes 36 PVT collectors with every 6 PVT collectors connected in series. The thermal energy generation, thermal efficiency, power generation and photovoltaic efficiency have been given in this paper. The results demonstrate that the demonstration solar PVT cogeneration system can meet the building energy demand in the daytime in the heating season.

RECENT ADVANCES TOWARDS THE RATIONAL DESIGN OF PEPTIDE DRUGS

OpenAIRE

YEŞİLADA, Akgül; ÖZKANLI, Fügen

2004-01-01

In this review, after a short introduction to definition and physiological roles of regulatory peptides, problems faced during the development of peptide drugs, studies directed to solve these problems and rational design of peptide drugs with special emphesis on peptidomimetics are mentioned

Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

Science.gov (United States)

Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

2010-09-01

We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

On-Demand Telemetry

Data.gov (United States)

National Aeronautics and Space Administration — AFRC has previously investigated the use of Network Based Telemetry. We will be building on that research to enable On-Demand Telemetry. On-Demand Telemetry is a way...

Crystallography and Drug Design

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 12. Crystallography and Drug Design. K Suguna. General Article Volume 19 Issue 12 December 2014 pp 1093-1103. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/019/12/1093-1103. Keywords.

Fragment-based drug design.

Science.gov (United States)

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.

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

Science.gov (United States)

Musselman, Megan E; Hampton, Jeremy P

2014-07-01

Synthetic, or "designer" drugs, are created by manipulating the chemical structures of other psychoactive drugs so that the resulting product is structurally similar but not identical to illegal psychoactive drugs. Originally developed in the 1960s as a way to evade existing drug laws, the use of designer drugs has increased dramatically over the past few years. These drugs are deceptively packaged as "research chemicals," "incense," "bath salts," or "plant food," among other names, with labels that may contain warnings such as "not for human consumption" or "not for sale to minors." The clinical effects of most new designer drugs can be described as either hallucinogenic, stimulant, or opioid-like. They may also have a combination of these effects due to designer side-chain substitutions. The easy accessibility and rapid emergence of new designer drugs have created challenges for health care providers when treating patients presenting with acute toxicity from these substances, many of which can produce significant and/or life-threatening adverse effects. Moreover, the health care provider has no way to verify the contents and/or potency of the agent ingested because it can vary between packages and distributors. Therefore, a thorough knowledge of the available designer drugs, common signs and symptoms of toxicity associated with these agents, and potential effective treatment modalities are essential to appropriately manage these patients. © 2014 Pharmacotherapy Publications, Inc.

Monitoring the size and protagonists of the drug market: combining supply and demand data sources and estimates.

Science.gov (United States)

Rossi, Carla

2013-06-01

The size of the illicit drug market is an important indicator to assess the impact on society of an important part of the illegal economy and to evaluate drug policy and law enforcement interventions. The extent of illicit drug use and of the drug market can essentially only be estimated by indirect methods based on indirect measures and on data from various sources, as administrative data sets and surveys. The combined use of several methodologies and data sets allows to reduce biases and inaccuracies of estimates obtained on the basis of each of them separately. This approach has been applied to Italian data. The estimation methods applied are capture-recapture methods with latent heterogeneity and multiplier methods. Several data sets have been used, both administrative and survey data sets. First, the retail dealer prevalence has been estimated on the basis of administrative data, then the user prevalence by multiplier methods. Using information about behaviour of dealers and consumers from survey data, the average amount of a substance used or sold and the average unit cost have been estimated and allow estimating the size of the drug market. The estimates have been obtained using a supply-side approach and a demand-side approach and have been compared. These results are in turn used for estimating the interception rate for the different substances in term of the value of the substance seized with respect to the total value of the substance to be sold at retail prices.

Design and Evaluation of Chitosan-Based Novel pHSensitive Drug ...

African Journals Online (AJOL)

Design and Evaluation of Chitosan-Based Novel pHSensitive Drug Carrier for Sustained ... Scanning electron microscopy(SEM),Raman spectroscopy for particle size analysis. Swelling ratio, Effect of drug loading on encapsulation efficiency

Designing a scalable video-on-demand server with data sharing

Science.gov (United States)

Lim, Hyeran; Du, David H. C.

2001-01-01

As current disk space and transfer speed increase, the bandwidth between a server and its disks has become critical for video-on-demand (VOD) services. Our VOD server consists of several hosts sharing data on disks through a ring-based network. Data sharing provided by the spatial-reuse ring network between servers and disks not only increases the utilization towards full bandwidth but also improves the availability of videos. Striping and replication methods are introduced in order to improve the efficiency of our VOD server system as well as the availability of videos. We consider tow kinds of resources of a VOD server system. Given a representative access profile, our intention is to propose an algorithm to find an initial condition, place videos on disks in the system successfully. If any copy of a video cannot be placed due to lack of resources, more servers/disks are added. When all videos are place on the disks by our algorithm, the final configuration is determined with indicator of how tolerable it is against the fluctuation in demand of videos. Considering it is a NP-hard problem, our algorithm generates the final configuration with O(M log M) at best, where M is the number of movies.

On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations for relevant ejaculation delay and consequent solutions.

Science.gov (United States)

Waldinger, Marcel D; Schweitzer, Dave H; Olivier, Berend

2005-01-01

Recently, the idea has emerged that on-demand use of serotonin reuptake inhibitors (SSRIs), particularly short half-life, should be equally effective in delaying ejaculation as daily SSRI treatment of premature ejaculation. To provide evidence that SSRI-induced ejaculation delay is mainly dependent on pharmacodynamic properties of the drug and hardly on pharmacokinetic factors, and that combined SSRI administration with specific 5-hydroxytryptamine (5-HT) receptor antagonism leads acutely to stronger ejaculation delay than acute SSRI monoadministration. We performed a detailed analysis of serotonin neurotransmission and reviewed animal studies with 5-HT(1A) receptor antagonists. In addition, we critically reviewed existing on-demand SSRI treatments publications and the current debate on a definition of premature ejaculation. Intravaginal ejaculation latency time (IELT). Acute SSRI administration leads to only a mild or no increase of 5-HT neurotransmission and concomitant stimulation of postsynaptic 5-HT receptors. Existing on-demand SSRI treatment studies suffer from methodological insufficiencies, and the reported high-fold increases of ejaculation time contradict with neuropharmacological insights from serotonin metabolism. Animal studies show that SSRI coadministration with 5-HT(1A) receptor antagonists significantly increases the ejaculation time acutely compared to acute SSRI monoadministration. On-demand SSRI treatment has less ejaculation-delaying effects than daily SSRI treatment. SSRIs with a short half-life are likely leading to much less ejaculation delay than current registered SSRIs. Combined use of SSRIs with 5-HT(1A) receptor antagonists increases the likelihood of clinically relevant ejaculation delay after on-demand treatment. On-demand SSRIs with short half-life that insufficiently delay ejaculation in men with IELTs less than 1 minute should be called ejaculation-delaying drugs rather than drugs against premature ejaculation.

A Novel Design for Drug-Drug Interaction Alerts Improves Prescribing Efficiency.

Science.gov (United States)

Russ, Alissa L; Chen, Siying; Melton, Brittany L; Johnson, Elizabette G; Spina, Jeffrey R; Weiner, Michael; Zillich, Alan J

2015-09-01

Drug-drug interactions (DDIs) are common in clinical care and pose serious risks for patients. Electronic health records display DDI alerts that can influence prescribers, but the interface design of DDI alerts has largely been unstudied. In this study, the objective was to apply human factors engineering principles to alert design. It was hypothesized that redesigned DDI alerts would significantly improve prescribers' efficiency and reduce prescribing errors. In a counterbalanced, crossover study with prescribers, two DDI alert designs were evaluated. Department of Veterans Affairs (VA) prescribers were video recorded as they completed fictitious patient scenarios, which included DDI alerts of varying severity. Efficiency was measured from time-stamped recordings. Prescribing errors were evaluated against predefined criteria. Efficiency and prescribing errors were analyzed with the Wilcoxon signed-rank test. Other usability data were collected on the adequacy of alert content, prescribers' use of the DDI monograph, and alert navigation. Twenty prescribers completed patient scenarios for both designs. Prescribers resolved redesigned alerts in about half the time (redesign: 52 seconds versus original design: 97 seconds; p<.001). Prescribing errors were not significantly different between the two designs. Usability results indicate that DDI alerts might be enhanced by facilitating easier access to laboratory data and dosing information and by allowing prescribers to cancel either interacting medication directly from the alert. Results also suggest that neither design provided adequate information for decision making via the primary interface. Applying human factors principles to DDI alerts improved overall efficiency. Aspects of DDI alert design that could be further enhanced prior to implementation were also identified.

The evolution of drug design at Merck Research Laboratories.

Science.gov (United States)

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

2017-03-01

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

The evolution of drug design at Merck Research Laboratories

Science.gov (United States)

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

2017-03-01

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

History of demand side management and classification of demand response control schemes

NARCIS (Netherlands)

Lampropoulos, I.; Kling, W.L.; Ribeiro, P.F.; Berg, van den J.

2013-01-01

The scope of this paper is to provide a review on the topic of demand side management. A historical overview provides a critical insight to applied cases, while the discovery of new evidence calls for reconsideration of the design of demand response control schemes. The developments at the demand

New designer drugs (synthetic cannabinoids and synthetic cathinones): review of literature.

Science.gov (United States)

Cottencin, Olivier; Rolland, Benjamin; Karila, Laurent

2014-01-01

New designer drugs (synthetic cannabinoids and synthetic cathinones) are new "legal highs" that are sold online for recreational public or private use. Synthetic cannabinoids are psychoactive herbal and chemical products that mimic the effects of cannabis when used. These drugs are available on the Internet or in head shops as incense or air fresheners to circumvent the law. Cathinone is a naturally occurring beta-ketone amphetamine analog found in the leaves of the Catha edulis plant. Synthetic cathinones are phenylalkylamine derivatives that may possess amphetamine-like properties. These drugs are sold online as bath salts. Designer drugs are often labeled as "not for human consumption" to circumvent drug abuse legislation. The absence of legal risks, the ease of obtaining these drugs, the moderate cost, and the availability via the Internet are the main features that attract users, but the number of intoxicated people presenting with emergencies is increasing. There is evidence that negative health and social consequences may affect recreational and chronic users. The addictive potential of designer drugs is not negligible.

Analysis and design of hospital management information system based on UML

Science.gov (United States)

Ma, Lin; Zhao, Huifang; You, Shi Jun; Ge, Wenyong

2018-05-01

With the rapid development of computer technology, computer information management system has been utilized in many industries. Hospital Information System (HIS) is in favor of providing data for directors, lightening the workload for the medical workers, and improving the workers efficiency. According to the HIS demand analysis and system design, this paper focus on utilizing unified modeling language (UML) models to establish the use case diagram, class diagram, sequence chart and collaboration diagram, and satisfying the demands of the daily patient visit, inpatient, drug management and other relevant operations. At last, the paper summarizes the problems of the system and puts forward an outlook of the HIS system.

Design optimization of a novel pMDI actuator for systemic drug delivery.

Science.gov (United States)

Kakade, Prashant P; Versteeg, Henk K; Hargrave, Graham K; Genova, Perry; Williams Iii, Robert C; Deaton, Daniel

2007-01-01

Pressurized metered dose inhalers (pMDIs) are the most widely prescribed and economical respiratory drug delivery systems. Conventional pMDI actuators-those based on "two-orifice-and-sump" designs-produce an aerosol with a reasonable respirable fraction, but with high aerosol velocity. The latter is responsible for high oropharyngeal deposition, and consequently low drug delivery efficiency. Kos' pMDI technology is based on a proprietary vortex nozzle actuator (VNA), an innovative actuator configuration that seeks to reduce aerosol plume velocity, thereby promoting deep lung deposition. Using VNA development as a case study, this paper presents a systematic design optimization process to improve the actuator performance through use of advanced optical characterization tools. The optimization effort mainly relied on laser-based optical diagnostics to provide an improved understanding of the fundamentals of aerosol formation and interplay of various geometrical factors. The performance of the optimized VNA design thus evolved was characterized using phase Doppler anemometry and cascade impaction. The aerosol velocities for both standard and optimized VNA designs were found to be comparable, with both notably less than conventional actuators. The optimized VNA design also significantly reduces drug deposition in the actuator as well as USP throat adapter, which in turn, leads to a significantly higher fine particle fraction than the standard design (78 +/- 3% vs. 63 +/- 2% on an ex valve basis). This improved drug delivery efficiency makes VNA technology a practical proposition as a systemic drug delivery platform. Thus, this paper demonstrates how advanced optical diagnostic and characterization tools can be used in the development of high efficiency aerosol drug delivery devices.

Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

Science.gov (United States)

Kesisoglou, Filippos; Mitra, Amitava

2015-09-01

Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

77 FR 9946 - Draft Guidance for Industry on Drug Interaction Studies-Study Design, Data Analysis, Implications...

Science.gov (United States)

2012-02-21

... industry entitled ``Drug Interaction Studies--Study Design, Data Analysis, Implications for Dosing, and... data analysis in the context of identifying potential drug interactions. The guidance also addresses... Studies--Study Design, Data Analysis, and Implications for Dosing and Labeling.'' Comments were received...

Tiered co-payments, pricing, and demand in reference price markets for pharmaceuticals.

Science.gov (United States)

Herr, Annika; Suppliet, Moritz

2017-12-01

Health insurance companies curb price-insensitive behavior and the moral hazard of insureds by means of cost-sharing, such as tiered co-payments or reference pricing in drug markets. This paper evaluates the effect of price limits - below which drugs are exempt from co-payments - on prices and on demand. First, using a difference-in-differences estimation strategy, we find that the new policy decreases prices by 5 percent for generics and increases prices by 4 percent for brand-name drugs in the German reference price market. Second, estimating a nested-logit demand model, we show that consumers appreciate co-payment exempt drugs and calculate lower price elasticities for brand-name drugs than for generics. This explains the different price responses of brand-name and generic drugs and shows that price-related co-payment tiers are an effective tool to steer demand to low-priced drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Composition-property relationships in multifunctional hollow mesoporous carbon nanosystems for PH-responsive magnetic resonance imaging and on-demand drug release

Science.gov (United States)

Zhang, Shengjian; Qian, Xiaoqing; Zhang, Linlin; Peng, Weijun; Chen, Yu

2015-04-01

The construction of intelligent stimuli-responsive nanosystems can substantially improve the sensitivity/resolution/specificity of diagnostic imaging and enhance the therapeutic efficiency of chemotherapy for cancer treatment. This work reports on a generic construction strategy to achieve a multiple stimuli-responsive theranostic system for cancer simply by optimizing the chemical compositions of inorganic nanoplatforms to avoid the tedious and complicated synthetic procedure for traditional organic or organic/inorganic nanosystems. Based on the ``breaking up'' nature of manganese oxides and specific features of the carbonaceous framework to interact with aromatic drug molecules, manganese oxide nanoparticles were elaborately integrated into hollow mesoporous carbon nanocapsules by a simple in situ framework redox strategy to realize concurrent pH-sensitive T1-weighted magnetic resonance imaging (MRI) and pH-/HIFU-responsive on-demand drug release. The ultrasensitive disease-triggered MRI performance has been successfully demonstrated by a 52.5-fold increase of longitudinal relaxivity (r1 = 10.5 mM-1 s-1) and on nude mice 4T1 xenograft. The pH- and HIFU-triggered doxorubicin release and enhanced therapeutic outcome against multidrug resistance of cancer cells were systematically confirmed. In particular, the fabricated inorganic composite nanocapsules were found to feature unique biological behaviours, such as antimetastasis effect, extremely low hemolysis against red blood cells and high in vivo histocompatibility. This report on the successful construction of a pure inorganic nanosystem with multiple stimuli-responsivenesses may pave the way to new methods for the development of intelligent nanofamilies for cancer therapy.The construction of intelligent stimuli-responsive nanosystems can substantially improve the sensitivity/resolution/specificity of diagnostic imaging and enhance the therapeutic efficiency of chemotherapy for cancer treatment. This work reports

Projected Demand and Potential Impacts to the National Airspace System of Autonomous, Electric, On-Demand Small Aircraft

Science.gov (United States)

Smith, Jeremy C.; Viken, Jeffrey K.; Guerreiro, Nelson M.; Dollyhigh, Samuel M.; Fenbert, James W.; Hartman, Christopher L.; Kwa, Teck-Seng; Moore, Mark D.

2012-01-01

Electric propulsion and autonomy are technology frontiers that offer tremendous potential to achieve low operating costs for small-aircraft. Such technologies enable simple and safe to operate vehicles that could dramatically improve regional transportation accessibility and speed through point-to-point operations. This analysis develops an understanding of the potential traffic volume and National Airspace System (NAS) capacity for small on-demand aircraft operations. Future demand projections use the Transportation Systems Analysis Model (TSAM), a tool suite developed by NASA and the Transportation Laboratory of Virginia Polytechnic Institute. Demand projections from TSAM contain the mode of travel, number of trips and geographic distribution of trips. For this study, the mode of travel can be commercial aircraft, automobile and on-demand aircraft. NASA's Airspace Concept Evaluation System (ACES) is used to assess NAS impact. This simulation takes a schedule that includes all flights: commercial passenger and cargo; conventional General Aviation and on-demand small aircraft, and operates them in the simulated NAS. The results of this analysis projects very large trip numbers for an on-demand air transportation system competitive with automobiles in cost per passenger mile. The significance is this type of air transportation can enhance mobility for communities that currently lack access to commercial air transportation. Another significant finding is that the large numbers of operations can have an impact on the current NAS infrastructure used by commercial airlines and cargo operators, even if on-demand traffic does not use the 28 airports in the Continental U.S. designated as large hubs by the FAA. Some smaller airports will experience greater demand than their current capacity allows and will require upgrading. In addition, in future years as demand grows and vehicle performance improves other non-conventional facilities such as short runways incorporated into

A structural keystone for drug design

Directory of Open Access Journals (Sweden)

Rother Kristian

2006-06-01

Full Text Available 3D-structures of proteins and potential ligands are the cornerstones of rational drug design. The first brick to build upon is selecting a protein target and finding out whether biologically active compounds are known. Both tasks require more information than the structures themselves provide. For this purpose we have built a web resource bridging protein and ligand databases. It consists of three parts: i A data warehouse on annotation of protein structures that integrates many well-known databases such as Swiss-Prot, SCOP, ENZYME and others. ii A conformational library of structures of approved drugs. iii A conformational library of ligands from the PDB, linking the realms of proteins and small molecules.

Quantum mechanics implementation in drug-design workflows: does it really help? [Corrigendum

Directory of Open Access Journals (Sweden)

Arodola OA

2017-11-01

Full Text Available Arodola OA, Soliman MES. Quantum mechanics implementation in drug-design workflows: does it really help? Drug Design, Development and Therapy. 2017;11:2551–2564.Figure 3 on page 2557 contains errors. The correct figure is shown.Read the original article

Competitive closed-loop supply chain network design with price-dependent demands

DEFF Research Database (Denmark)

Rezapour, Shabnam; Farahani, Reza Zanjirani; Fahimnia, Behnam

2015-01-01

Abstract This paper presents a bi-level model for the strategic reverse network design (upper level) and tactical/operational planning (lower level) of a closed-loop single-period supply chain operating in a competitive environment with price-dependent market demand. An existing supply chain (SC...... for the supply of new and remanufactured products. The performance behaviors of both SCs are evaluated with specific focus placed on investigating the impacts of the strategic facility location decisions of the new SC on the tactical/operational transport and inventory decisions of the overall network. The bi...

A robust optimization model for green regional logistics network design with uncertainty in future logistics demand

Directory of Open Access Journals (Sweden)

Dezhi Zhang

2015-12-01

Full Text Available This article proposes a new model to address the design problem of a sustainable regional logistics network with uncertainty in future logistics demand. In the proposed model, the future logistics demand is assumed to be a random variable with a given probability distribution. A set of chance constraints with regard to logistics service capacity and environmental impacts is incorporated to consider the sustainability of logistics network design. The proposed model is formulated as a two-stage robust optimization problem. The first-stage problem before the realization of future logistics demand aims to minimize a risk-averse objective by determining the optimal location and size of logistics parks with CO2 emission taxes consideration. The second stage after the uncertain logistics demand has been determined is a scenario-based stochastic logistics service route choices equilibrium problem. A heuristic solution algorithm, which is a combination of penalty function method, genetic algorithm, and Gauss–Seidel decomposition approach, is developed to solve the proposed model. An illustrative example is given to show the application of the proposed model and solution algorithm. The findings show that total social welfare of the logistics system depends very much on the level of uncertainty in future logistics demand, capital budget for logistics parks, and confidence levels of the chance constraints.

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

International Nuclear Information System (INIS)

Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J

2011-01-01

Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s -1 . Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

Science.gov (United States)

Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

2011-02-01

Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

Energy Technology Data Exchange (ETDEWEB)

Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J, E-mail: Thomas_Webster@Brown.edu [School of Engineering, Brown University, Providence, RI 02912 (United States)

2011-02-25

Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s{sup -1}. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

A multi-period distribution network design model under demand uncertainty

Science.gov (United States)

Tabrizi, Babak H.; Razmi, Jafar

2013-05-01

Supply chain management is taken into account as an inseparable component in satisfying customers' requirements. This paper deals with the distribution network design (DND) problem which is a critical issue in achieving supply chain accomplishments. A capable DND can guarantee the success of the entire network performance. However, there are many factors that can cause fluctuations in input data determining market treatment, with respect to short-term planning, on the one hand. On the other hand, network performance may be threatened by the changes that take place within practicing periods, with respect to long-term planning. Thus, in order to bring both kinds of changes under control, we considered a new multi-period, multi-commodity, multi-source DND problem in circumstances where the network encounters uncertain demands. The fuzzy logic is applied here as an efficient tool for controlling the potential customers' demand risk. The defuzzifying framework leads the practitioners and decision-makers to interact with the solution procedure continuously. The fuzzy model is then validated by a sensitivity analysis test, and a typical problem is solved in order to illustrate the implementation steps. Finally, the formulation is tested by some different-sized problems to show its total performance.

Exploring Demand Charge Savings from Commercial Solar

Energy Technology Data Exchange (ETDEWEB)

Darghouth, Naim [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Barbose, Galen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mills, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wiser, Ryan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gagnon, Pieter [National Renewable Energy Lab. (NREL), Golden, CO (United States); Bird, Lori [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2017-07-31

Commercial retail electricity rates commonly include a demand charge component, based on some measure of the customer’s peak demand. Customer-sited solar PV can potentially reduce demand charges, but the magnitude of these savings can be difficult to predict, given variations in demand charge designs, customer loads, and PV generation profiles. Moreover, depending on the circumstances, demand charges from solar may or may not align well with associated utility cost savings. Lawrence Berkeley National Laboratory (Berkeley Lab) and the National Renewable Energy Laboratory (NREL) are collaborating in a series of studies to understand how solar PV can reduce demand charge levels for a variety of customer types and demand charges designs. Previous work focused on residential customs with solar. This study, instead, focuses on commercial customers and seeks to understand the extent and conditions under which rooftop can solar reduce commercial demand charges. To answer these questions, we simulate demand charge savings for a broad range of commercial customer types, demand charge designs, locations, and PV system characteristics. This particular analysis does not include storage, but a subsequent analysis in this series will evaluate demand charge savings for commercial customers with solar and storage.

Low-Carbon Warehousing: Examining Impacts of Building and Intra-Logistics Design Options on Energy Demand and the CO2 Emissions of Logistics Centers

Directory of Open Access Journals (Sweden)

Julia Freis

2016-05-01

Full Text Available Logistics centers contribute to CO2 emissions in the building and logistics sector and therefore share a responsibility to decarbonize not only the supply chain. Synergy effects in both building and intra-logistics should be considered as suitable levers to lower energy demand and related CO2 emissions. This research develops firs t with a systemic approach an integrated analytical model for energy calculation and reference building models for different types of logistics centers to provide basic knowledge and a methodological framework for planners and managers to aid in the selection of different intra-logistics and building design options for optimum energy efficiency. It then determines the energy demand in reference building models and performs parameter studies to examine interrelations and impacts of design options for intra-logistics, building technology, and building skin on energy demand. It combines these to optimized reference building models to show the extent to which energy and CO2 emission savings can be reached. The results show that it is possible to significantly lower CO2 emissions. However, there are clear differences between the different types of logistics centers and the impacts of different design options.

Impact of Rate Design Alternatives on Residential Solar Customer Bills. Increased Fixed Charges, Minimum Bills and Demand-based Rates

Energy Technology Data Exchange (ETDEWEB)

Bird, Lori [National Renewable Energy Lab. (NREL), Golden, CO (United States); Davidson, Carolyn [National Renewable Energy Lab. (NREL), Golden, CO (United States); McLaren, Joyce [National Renewable Energy Lab. (NREL), Golden, CO (United States); Miller, John [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2015-09-01

With rapid growth in energy efficiency and distributed generation, electric utilities are anticipating stagnant or decreasing electricity sales, particularly in the residential sector. Utilities are increasingly considering alternative rates structures that are designed to recover fixed costs from residential solar photovoltaic (PV) customers with low net electricity consumption. Proposed structures have included fixed charge increases, minimum bills, and increasingly, demand rates - for net metered customers and all customers. This study examines the electricity bill implications of various residential rate alternatives for multiple locations within the United States. For the locations analyzed, the results suggest that residential PV customers offset, on average, between 60% and 99% of their annual load. However, roughly 65% of a typical customer's electricity demand is non-coincidental with PV generation, so the typical PV customer is generally highly reliant on the grid for pooling services.

Coloring versus Drawing: Effects of Cognitive Demand on Mood Repair, Flow, and Enjoyment

Science.gov (United States)

Forkosh, Jennifer; Drake, Jennifer E.

2017-01-01

We examined whether using drawing to distract, by either coloring a design or drawing a design, improves mood more than drawing to express feelings. We manipulated levels of cognitive demand in the first 2 conditions by asking participants to color a design (low cognitive demand) or draw a design (high cognitive demand). After a sad mood…

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

KAUST Repository

Zaher, A.

2015-09-29

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices\\' drug diffusion rates are on the order of 0.5–2 μg/h for higher release rate designs, and 12–40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source.

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

KAUST Repository

Zaher, Amir; Li, S.; Wolf, K. T.; Pirmoradi, F. N.; Yassine, Omar; Lin, L.; Khashab, Niveen M.; Kosel, Jü rgen

2015-01-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5–2 μg/h for higher release rate designs, and 12–40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source.

Effect of demand management on regulated and deregulated electricity sectors

International Nuclear Information System (INIS)

Fahrioglu, Murat

2016-01-01

Our society derives a quantifiable benefit from electric power. In particular, forced outages or blackouts have enormous consequences on society, one of which is loss of economic surplus. The society relies on having a continuous supply of electrical energy. Some customers may willingly risk this continuous supply and participate in demand management programs for electrical power. If the power system grid is in trouble, electric utilities need to have demand relief. Customers willing to reduce their demand to help the system can receive an incentive fee for helping the utilities. Demand relief can be system wide or location specific. Sometimes it can be more effective to fix the electrical demand vs. supply imbalance from the demand side. The value of demand management contracts is greatly affected by customer location. Inclusion of locational attributes into the contract design procedure increases the effectiveness of the contracts by helping a utility get more value from its demand management programs. Independent System Operators and regulators, among others, can also benefit from effective demand management. This paper will investigate how this type of demand management contracts can help the electricity sector both in regulated and deregulated environments. - Highlights: • Demand management can help prevent forced electricity outages. • Both electric utilities and ISOs can use demand management. • Regulated and deregulated electricity sectors can benefit from demand management. • Demand management contracts can be effectively used in power system grids.

The Value of Specialty Oncology Drugs

Science.gov (United States)

Goldman, Dana P; Jena, Anupam B; Lakdawalla, Darius N; Malin, Jennifer L; Malkin, Jesse D; Sun, Eric

2010-01-01

Objective To estimate patients' elasticity of demand, willingness to pay, and consumer surplus for five high-cost specialty medications treating metastatic disease or hematologic malignancies. Data Source/Study Setting Claims data from 71 private health plans from 1997 to 2005. Study Design This is a revealed preference analysis of the demand for specialty drugs among cancer patients. We exploit differences in plan generosity to examine how utilization of specialty oncology drugs varies with patient out-of-pocket costs. Data Collection/Extraction Methods We extracted key variables from administrative health insurance claims records. Principal Findings A 25 percent reduction in out-of-pocket costs leads to a 5 percent increase in the probability that a patient initiates specialty cancer drug therapy. Among patients who initiate, a 25 percent reduction in out-of-pocket costs reduces the number of treatments (claims) by 1–3 percent, depending on the drug. On average, the value of these drugs to patients who use them is about four times the total cost paid by the patient and his or her insurer, although this ratio may be lower for oral specialty therapies. Conclusions The decision to initiate therapy with specialty oncology drugs is responsive to price, but not highly so. Among patients who initiate therapy, the amount of treatment is equally responsive. The drugs we examine are highly valued by patients in excess of their total costs, although oral agents warrant further scrutiny as copayments increase. PMID:19878344

Skin Permeation Enhancers and their Effects on Narcotic Transdermal Drug Delivery Systems through Response Surface Experimental Design

Directory of Open Access Journals (Sweden)

A. Moghimi

2014-02-01

Full Text Available Drug delivery through skin is often obstructed by low permeability of skin towards most drugs; however, such problem would be solved by application of skin penetration enhancers in the formulations. In the present study, a drug in adhesive patch with buprenorphine as active ingredient was prepared. Drug-in-adhesive transdermal drug delivery systems with different chemical penetration enhancers were designed. For this purpose a response-surface experimental design was used. Response surface methodology based on a three-level, three-variable Box–Behnken design was used to evaluate the interactive effects of dependent variables such as: the rate of skin permeation and adhesion properties including peel strength and tack value. The parameters such as drug release and adhesion were used as independent variables. Levulinic acid, lauryl alcohol and Tween 80 were used as penetration enhancers. In order to prepare samples, buprenorphine with constant concentration was incorporated into acrylic pressure sensitive adhesive with carboxylic functionality and this mixture was added to chemical penetration enhancer with different concentrations. The results show that the cumulative amount of drug release in presence of Tween 80 is 462.9 ± 0.006 μg so it is higher than cumulative amount of drug release in presence of levulinic acid (357.9 ± 0.005 μg and lauryl alcohol (269.5 ± 0.001 μg. Results of adhesion properties such as peel strength and tack reveal that using levulinic acid and lauryl alcohol will increase peel strength while Tween 80 will decrease it. Besides, the results show that all these permeation enhancers have increased tack values.

Pyrimidines in antimalarial drug design

CSIR Research Space (South Africa)

Moleele, SS

2008-09-01

Full Text Available of the routes attempted are shown in Scheme 1. Pyrimidines In Antimalarial Drug Design S S Moleele1, D Gravestock1, A L Rousseau1, R L Van Zyl2 1Discovery Chemistry, CSIR, Biosciences, Private Bag X2, Modderfontein, 1645, South Africa; SMoleele@csir.co.za 2...

Heroin and saccharin demand and preference in rats.

Science.gov (United States)

Schwartz, Lindsay P; Kim, Jung S; Silberberg, Alan; Kearns, David N

2017-09-01

Several recent studies have investigated the choice between heroin and a non-drug alternative reinforcer in rats. A common finding in these studies is that there are large individual differences in preference, with some rats preferring heroin and some preferring the non-drug alternative. The primary goal of the present study was to determine whether individual differences in how heroin or saccharin is valued, based on demand analysis, predicts choice. Rats lever-pressed for heroin infusions and saccharin reinforcers on fixed-ratio schedules. The essential value of each reinforcer was obtained from resulting demand curves. Rats were then trained on a mutually exclusive choice procedure where pressing one lever resulted in heroin and pressing another resulted in saccharin. After seven sessions of increased access to heroin or saccharin, rats were reexposed to the demand and choice procedures. Demand for heroin was more elastic than demand for saccharin (i.e., heroin had lower essential value than saccharin). When allowed to choose, most rats preferred saccharin. The essential value of heroin, but not saccharin, predicted preference. The essential value of both heroin and saccharin increased following a week of increased access to heroin, but similar saccharin exposure had no effect on essential value. Preference was unchanged after increased access to either reinforcer. Heroin-preferring rats differed from saccharin-preferring rats in how they valued heroin, but not saccharin. To the extent that choice models addiction-related behavior, these results suggest that overvaluation of opioids specifically, rather than undervaluation of non-drug alternatives, could identify susceptible individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

A Bayesian hierarchical model for demand curve analysis.

Science.gov (United States)

Ho, Yen-Yi; Nhu Vo, Tien; Chu, Haitao; Luo, Xianghua; Le, Chap T

2018-07-01

Drug self-administration experiments are a frequently used approach to assessing the abuse liability and reinforcing property of a compound. It has been used to assess the abuse liabilities of various substances such as psychomotor stimulants and hallucinogens, food, nicotine, and alcohol. The demand curve generated from a self-administration study describes how demand of a drug or non-drug reinforcer varies as a function of price. With the approval of the 2009 Family Smoking Prevention and Tobacco Control Act, demand curve analysis provides crucial evidence to inform the US Food and Drug Administration's policy on tobacco regulation, because it produces several important quantitative measurements to assess the reinforcing strength of nicotine. The conventional approach popularly used to analyze the demand curve data is individual-specific non-linear least square regression. The non-linear least square approach sets out to minimize the residual sum of squares for each subject in the dataset; however, this one-subject-at-a-time approach does not allow for the estimation of between- and within-subject variability in a unified model framework. In this paper, we review the existing approaches to analyze the demand curve data, non-linear least square regression, and the mixed effects regression and propose a new Bayesian hierarchical model. We conduct simulation analyses to compare the performance of these three approaches and illustrate the proposed approaches in a case study of nicotine self-administration in rats. We present simulation results and discuss the benefits of using the proposed approaches.

Medicinal Chemistry Projects Requiring Imaginative Structure-Based Drug Design Methods.

Science.gov (United States)

Moitessier, Nicolas; Pottel, Joshua; Therrien, Eric; Englebienne, Pablo; Liu, Zhaomin; Tomberg, Anna; Corbeil, Christopher R

2016-09-20

Computational methods for docking small molecules to proteins are prominent in drug discovery. There are hundreds, if not thousands, of documented examples-and several pertinent cases within our research program. Fifteen years ago, our first docking-guided drug design project yielded nanomolar metalloproteinase inhibitors and illustrated the potential of structure-based drug design. Subsequent applications of docking programs to the design of integrin antagonists, BACE-1 inhibitors, and aminoglycosides binding to bacterial RNA demonstrated that available docking programs needed significant improvement. At that time, docking programs primarily considered flexible ligands and rigid proteins. We demonstrated that accounting for protein flexibility, employing displaceable water molecules, and using ligand-based pharmacophores improved the docking accuracy of existing methods-enabling the design of bioactive molecules. The success prompted the development of our own program, Fitted, implementing all of these aspects. The primary motivation has always been to respond to the needs of drug design studies; the majority of the concepts behind the evolution of Fitted are rooted in medicinal chemistry projects and collaborations. Several examples follow: (1) Searching for HDAC inhibitors led us to develop methods considering drug-zinc coordination and its effect on the pKa of surrounding residues. (2) Targeting covalent prolyl oligopeptidase (POP) inhibitors prompted an update to Fitted to identify reactive groups and form bonds with a given residue (e.g., a catalytic residue) when the geometry allows it. Fitted-the first fully automated covalent docking program-was successfully applied to the discovery of four new classes of covalent POP inhibitors. As a result, efficient stereoselective syntheses of a few screening hits were prioritized rather than synthesizing large chemical libraries-yielding nanomolar inhibitors. (3) In order to study the metabolism of POP inhibitors by

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

Science.gov (United States)

Furlong, Michael; Seong, Jae Young

2017-01-01

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

Achieving a Launch on Demand Capability

Science.gov (United States)

Greenberg, Joel S.

2002-01-01

-orbit availability. Results of an analysis are presented. The implications of launch on demand are addressed for each of the above three situations and related architecture performance metrics and computer simulation models are described that may be used to evaluate the implications of architecture and policy changes in terms of LOD requirements. The models and metrics are aimed at providing answers to such questions as: How well does a specified space transportation architecture respond to satellite launch demand and changes thereto? How well does a normally functioning and apparently architecture respond to unanticipated needs? What is the effect of a modification to the architecture on its ability to respond to satellite launch demand, including responding to unanticipated needs? What is the cost of the architecture [including facilities, operations, inventory, and satellites]? What is the sensitivity of overall architecture effectiveness and cost to various transportation system delays? What is the effect of adding [or eliminating] a launch vehicle or family of vehicles to [from] the architecture on its effectiveness and cost? What is the value of improving launch vehicle and satellite compatibility and what are the effects on probability of delay statistics and cost of designing for multi-launch vehicle compatibility

Molecular docking as a popular tool in drug design, an in silico travel

Directory of Open Access Journals (Sweden)

de Ruyck J

2016-06-01

Full Text Available Jerome de Ruyck, Guillaume Brysbaert, Ralf Blossey, Marc F Lensink University Lille, CNRS UMR8576 UGSF, Lille, FranceAbstract: New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism- or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Second, we present recent advances in anti-infectious agents' synthesis driven by structural insights. At the end, we focus on larger biological complexes made by protein–protein interactions and discuss their relevance in drug design. This review provides information on how these large systems, even in the presence of the solvent, can be investigated with the outlook of drug discovery.Keywords: structure-based drug design, protein–protein docking, quaternary structure prediction, residue interaction networks, RINs, water position

On energy demand

International Nuclear Information System (INIS)

Haefele, W.

1977-01-01

Since the energy crisis, a number of energy plans have been proposed, and almost all of these envisage some kind of energy demand adaptations or conservation measures, hoping thus to escape the anticipated problems of energy supply. However, there seems to be no clear explanation of the basis on which our foreseeable future energy problems could be eased. And in fact, a first attempt at a more exact definition of energy demand and its interaction with other objectives, such as economic ones, shows that it is a highly complex concept which we still hardly understand. The article explains in some detail why it is so difficult to understand energy demand

Designer drugs: how dangerous are they?

NARCIS (Netherlands)

Reneman, L.

2003-01-01

Of the designer drugs, the amphetamine analogues are the most popular and extensively studied, ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in particular. They are used recreationally with increasing popularity despite animal studies showing neurotoxic effects to serotonin (5-HT) and/or

The Open Form Inducer Approach for Structure-Based Drug Design.

Directory of Open Access Journals (Sweden)

Daniel Ken Inaoka

Full Text Available Many open form (OF structures of drug targets were obtained a posteriori by analysis of co-crystals with inhibitors. Therefore, obtaining the OF structure of a drug target a priori will accelerate development of potent inhibitors. In addition to its small active site, Trypanosoma cruzi dihydroorotate dehydrogenase (TcDHODH is fully functional in its monomeric form, making drug design approaches targeting the active site and protein-protein interactions unrealistic. Therefore, a novel a priori approach was developed to determination the TcDHODH active site in OF. This approach consists of generating an "OF inducer" (predicted in silico to bind the target and cause steric repulsion with flexible regions proximal to the active site that force it open. We provide the first proof-of-concept of this approach by predicting and crystallizing TcDHODH in complex with an OF inducer, thereby obtaining the OF a priori with its subsequent use in designing potent and selective inhibitors. Fourteen co-crystal structures of TcDHODH with the designed inhibitors are presented herein. This approach has potential to encourage drug design against diseases where the molecular targets are such difficult proteins possessing small AS volume. This approach can be extended to study open/close conformation of proteins in general, the identification of allosteric pockets and inhibitors for other drug targets where conventional drug design approaches are not applicable, as well as the effective exploitation of the increasing number of protein structures deposited in Protein Data Bank.

MPD3: a useful medicinal plants database for drug designing.

Science.gov (United States)

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

2017-06-01

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

Design and construction of a DNA origami drug delivery system based on MPT64 antibody aptamer for tuberculosis treatment.

Science.gov (United States)

Ranjbar, Reza; Hafezi-Moghadam, Mohammad Sadegh

2016-02-01

With all of the developments on infectious diseases, tuberculosis (TB) remains a cause of death among people. One of the most promising assembly techniques in nano-technology is "scaffolded DNA origami" to design and construct a nano-scale drug delivery system. Because of the global health problems of tuberculosis, the development of potent new anti-tuberculosis drug delivery system without cross-resistance with known anti-mycobacterial agents is urgently needed. The aim of this study was to design a nano-scale drug delivery system for TB treatment using the DNA origami method. In this study, we presented an experimental research on a DNA drug delivery system for treating Tuberculosis. TEM images were visualized with an FEI Tecnai T12 BioTWIN at 120 kV. The model was designed by caDNAno software and computational prediction of the 3D solution shape and its flexibility was calculated with a CanDo server. Synthesizing the product was imaged using transmission electron microscopy after negative-staining by uranyl formate. We constructed a multilayer 3D DNA nanostructure system by designing square lattice geometry with the scaffolded-DNA-origami method. With changes in the lock and key sequences, we recommend that this system be used for other infectious diseases to target the pathogenic bacteria.

Emergency response network design for hazardous materials transportation with uncertain demand

Directory of Open Access Journals (Sweden)

Kamran Shahanaghi

2012-10-01

Full Text Available Transportation of hazardous materials play an essential role on keeping a friendly environment. Every day, a substantial amount of hazardous materials (hazmats, such as flammable liquids and poisonous gases, need to be transferred prior to consumption or disposal. Such transportation may result in unsuitable events for people and environment. Emergency response network is designed for this reason where specialist responding teams resolve any issue as quickly as possible. This study proposes a new multi-objective model to locate emergency response centers for transporting the hazardous materials. Since many real-world applications are faced with uncertainty in input parameters, the proposed model of this paper also assumes that reference and demand to such centre is subject to uncertainty, where demand is fuzzy random. The resulted problem formulation is modelled as nonlinear non-convex mixed integer programming and we used NSGAII method to solve the resulted problem. The performance of the proposed model is examined with several examples using various probability distribution and they are compared with the performance of other existing method.

Global search demand for varicose vein information on the internet.

Science.gov (United States)

El-Sheikha, Joseph

2015-09-01

Changes in internet search trends can provide healthcare professionals detailed information on prevalence of disease and symptoms. Chronic venous disease, more commonly known as varicose veins, is a common symptomatic disease among the adult population. This study aims to measure the change in global search demand for varicose vein information using Google over the past 8 years. The Google Trends instrument was used to measure the change in demand for the use of the local name for varicose veins in several countries across the world between January 2006 and December 2012. The measurements were normalised onto a scale relative to the largest volume of search requests received during a designated time and geographical location. Comparison of national levels of private healthcare and healthcare spending per capita to search demand was also undertaken using Organisation for Economic Co-operation and development economic measurements. Global interest has increased significantly, with linear regression demonstrating a 3.72% year-on-year increase in demand over the 8-year time period (r(2 )= 0.385, p demand significantly increased in the northern hemisphere (p demand compared to cooler winter months (demand (r(2 )= 0.120 p = 0.306). Healthcare spending per capita did not relate to search demand (r(2 )= 0.450 p = 0.077). There is increasing demand for information about varicose veins on the internet, especially during the warmer months of the year. Online search demand does not appear to be related to healthcare spending. © The Author(s) 2014.

Recent advances in fluorination techniques and their anticipated impact on drug metabolism and toxicity.

Science.gov (United States)

Murphy, Cormac D; Sandford, Graham

2015-04-01

Fluorine's unique physicochemical properties make it a key element for incorporation into pharmacologically active compounds. Its presence in a drug can alter a number of characteristics that affect ADME-Tox, which has prompted efforts at improving synthetic fluorination procedures. This review describes the influence of fluorine on attributes such as potency, lipophilicity, metabolic stability and bioavailablility and how the effects observed are related to the physicochemical characteristics of the element. Examples of more recently used larger scale synthetic methods for introduction of fluorine into drug leads are detailed and the potential for using biological systems for fluorinated drug production is discussed. The synthetic procedures for carbon-fluorine bond formation largely still rely on decades-old technology for the manufacturing scale and new reagents and methods are required to meet the demands for the preparation of structurally more complex drugs. The improvement of in vitro and computational methods should make fluorinated drug design more efficient and place less emphasis on approaches such as fluorine scanning and animal studies. The introduction of new fluorinated drugs, and in particular those that have novel fluorinated functional groups, should be accompanied by rigorous environmental assessment to determine the nature of transformation products that may cause ecological damage.

An Automation System for Optimizing a Supply Chain Network Design under the Influence of Demand Uncertainty

OpenAIRE

Polany, Rany

2012-01-01

This research develops and applies an integrated hierarchical framework for modeling a multi-echelon supply chain network design, under the influence of demand uncertainty. The framework is a layered integration of two levels: macro, high-level scenario planning combined with micro, low-level Monte Carlo simulation of uncertainties in demand. To facilitate rapid simulation of the effects of demand uncertainty, the integrated framework was implemented as a dashboard automation system using Mic...

76 FR 44613 - Designation of Eight Counties as High Intensity Drug Trafficking Areas

Science.gov (United States)

2011-07-26

... OFFICE OF NATIONAL DRUG CONTROL POLICY Designation of Eight Counties as High Intensity Drug Trafficking Areas AGENCY: Office of National Drug Control Policy. ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy has designated eight additional counties as High Intensity Drug...

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

Energy Technology Data Exchange (ETDEWEB)

NONE

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.

Connecting drug delivery reality to smart materials design.

Science.gov (United States)

Grainger, David W

2013-09-15

Inflated claims to both design and mechanistic novelty in drug delivery and imaging systems, including most nanotechnologies, are not supported by the generally poor translation of these systems to clinical efficacy. The "form begets function" design paradigm is seductive but perhaps over-simplistic in translation to pharmaceutical efficacy. Most innovations show few clinically important distinctions in their therapeutic benefits in relevant preclinical disease and delivery models, despite frequent claims to the contrary. Long-standing challenges in drug delivery issues must enlist more realistic, back-to-basics approaches to address fundamental materials properties in complex biological systems, preclinical test beds, and analytical methods to more reliably determine fundamental pharmaceutical figures of merit, including drug carrier purity and batch-batch variability, agent biodistribution, therapeutic index (safety), and efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.

Science.gov (United States)

Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang

2017-08-18

The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Phytosterols and anabolic agents versus designer drugs

Energy Technology Data Exchange (ETDEWEB)

Brabander, H.F. de [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)]. E-mail: Hubert.DeBrabander@UGent.be; Verheyden, K. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Mortier, V. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Le Bizec, B. [LABERCA, Ecole Nationale Veterinaire de Nantes, BP 50707, F-44087 Nantes Cedex 03 (France); Verbeke, W. [Ghent University, Department of Agricultural Economics, Coupure links 653, B-9000 Ghent (Belgium); Courtheyn, D. [Federal Feed and Food Laboratory, Braemkasteelstraat 59, B-9050 Ghentbruges (Belgium); Noppe, H. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)

2007-03-14

Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the {sup 13}C/{sup 12}C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse.

Phytosterols and anabolic agents versus designer drugs

International Nuclear Information System (INIS)

Brabander, H.F. de; Verheyden, K.; Mortier, V.; Le Bizec, B.; Verbeke, W.; Courtheyn, D.; Noppe, H.

2007-01-01

Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the 13 C/ 12 C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse

Risk-taking related to drug use: an application of the shift-to-risk design.

Science.gov (United States)

Deren, S; Des Jarlais, D C

1977-01-01

The utility of the shift-to-risk design for studying the influence of peer groups on drug taking was investigated. Two studies using this design with drug content were conducted, varying the level of information provided about a drug. Subjects were from two college classes consisting of 26 and 28 students. Results indicated that the specification of possible harmful drug effects which are somewhat minimal lead to a significantly greater willingness to recommend trying the drug. In addition, a tendency for a shift-to-caution was found. It was concluded that the shift-to-risk designwas useful for studying decision-making regarding drug use, and that both users and nonusers of drugs should be included in future research.

Education on Demand

DEFF Research Database (Denmark)

Boysen, Lis; Hende, Merete

2015-01-01

Dette notat beskriver nogle af resultaterne fra programmet "Education on Demand' i projektet Det erhvervsrettede Uddannelseslaboratorium. Programmet har haft fokus på udfordringer og forandringsbehov i uddannelsesinstitutioner og -systemet. Herunder har det beskæftiget sig særligt med de to temat......Dette notat beskriver nogle af resultaterne fra programmet "Education on Demand' i projektet Det erhvervsrettede Uddannelseslaboratorium. Programmet har haft fokus på udfordringer og forandringsbehov i uddannelsesinstitutioner og -systemet. Herunder har det beskæftiget sig særligt med de...

Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design

Science.gov (United States)

Ishikawa, Toshihisa; Tamura, Ai; Saito, Hikaru; Wakabayashi, Kanako; Nakagawa, Hiroshi

2005-10-01

In the post-genome-sequencing era, emerging genomic technologies are shifting the paradigm for drug discovery and development. Nevertheless, drug discovery and development still remain high-risk and high-stakes ventures with long and costly timelines. Indeed, the attrition of drug candidates in preclinical and development stages is a major problem in drug design. For at least 30% of the candidates, this attrition is due to poor pharmacokinetics and toxicity. Thus, pharmaceutical companies have begun to seriously re-evaluate their current strategies of drug discovery and development. In that light, we propose that a transport mechanism-based design might help to create new, pharmacokinetically advantageous drugs, and as such should be considered an important component of drug design strategy. Performing enzyme- and/or cell-based drug transporter, interaction tests may greatly facilitate drug development and allow the prediction of drug-drug interactions. We recently developed methods for high-speed functional screening and quantitative structure-activity relationship analysis to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide a practical tool to screen synthetic and natural compounds, and these data can be applied to the molecular design of new drugs. In this review article, we present an overview on the genetic polymorphisms of human ABC transporter ABCG2 and new camptothecin analogues that can circumvent AGCG2-associated multidrug resistance of cancer.

Confusing the drug facts on one nonprescription drug label with those on another: The Drug Facts Label as a text schema

Directory of Open Access Journals (Sweden)

Michael P Ryan

2016-04-01

Full Text Available The Drug Facts Label is designed to guide consumers in comparing nonprescription drugs. Undergraduates studied and recalled drug facts for three analgesic or non-analgesic labels using Drug Facts Label headings as retrieval cues. They then studied and recalled drug facts from an aspirin label. Aspirin recall was greater when the prior labels were analgesics, but prior-label intrusion errors were also greater. These two effects were associated with the number of prior drug labels on which facilitating and interfering drug facts appeared. Using the Drug Facts Label schema to read drug labels can both enhance and degrade the recall of nonprescription drug facts.

Designing informative warning signals: Effects of indicator type, modality, and task demand on recognition speed and accuracy

Science.gov (United States)

Stevens, Catherine J.; Brennan, David; Petocz, Agnes; Howell, Clare

2009-01-01

An experiment investigated the assumption that natural indicators which exploit existing learned associations between a signal and an event make more effective warnings than previously unlearned symbolic indicators. Signal modality (visual, auditory) and task demand (low, high) were also manipulated. Warning effectiveness was indexed by accuracy and reaction time (RT) recorded during training and dual task test phases. Thirty-six participants were trained to recognize 4 natural and 4 symbolic indicators, either visual or auditory, paired with critical incidents from an aviation context. As hypothesized, accuracy was greater and RT was faster in response to natural indicators during the training phase. This pattern of responding was upheld in test phase conditions with respect to accuracy but observed in RT only in test phase conditions involving high demand and the auditory modality. Using the experiment as a specific example, we argue for the importance of considering the cognitive contribution of the user (viz., prior learned associations) in the warning design process. Drawing on semiotics and cognitive psychology, we highlight the indexical nature of so-called auditory icons or natural indicators and argue that the cogniser is an indispensable element in the tripartite nature of signification. PMID:20523852

Tablet fragmentation without a disintegrant: A novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets.

Science.gov (United States)

Arafat, Basel; Wojsz, Magdalena; Isreb, Abdullah; Forbes, Robert T; Isreb, Mohammad; Ahmed, Waqar; Arafat, Tawfiq; Alhnan, Mohamed A

2018-06-15

Fused deposition modelling (FDM) 3D printing has shown the most immediate potential for on-demand dose personalisation to suit particular patient's needs. However, FDM 3D printing often involves employing a relatively large molecular weight thermoplastic polymer and results in extended release pattern. It is therefore essential to fast-track drug release from the 3D printed objects. This work employed an innovative design approach of tablets with unique built-in gaps (Gaplets) with the aim of accelerating drug release. The novel tablet design is composed of 9 repeating units (blocks) connected with 3 bridges to allow the generation of 8 gaps. The impact of size of the block, the number of bridges and the spacing between different blocks was investigated. Increasing the inter-block space reduced mechanical resistance of the unit, however, tablets continued to meet pharmacopeial standards for friability. Upon introduction into gastric medium, the 1 mm spaces gaplet broke into mini-structures within 4 min and met the USP criteria of immediate release products (86.7% drug release at 30 min). Real-time ultraviolet (UV) imaging indicated that the cellulosic matrix expanded due to swelling of hydroxypropyl cellulose (HPC) upon introduction to the dissolution medium. This was followed by a steady erosion of the polymeric matrix at a rate of 8 μm/min. The design approach was more efficient than a comparison conventional formulation approach of adding disintegrants to accelerate tablet disintegration and drug release. This work provides a novel example where computer-aided design was instrumental at modifying the performance of solid dosage forms. Such an example may serve as the foundation for a new generation of dosage forms with complicated geometric structures to achieve functionality that is usually achieved by a sophisticated formulation approach. Copyright © 2018 Elsevier B.V. All rights reserved.

Designing container shipping network under changing demand and freight rates

Directory of Open Access Journals (Sweden)

C. Chen

2010-03-01

Full Text Available This paper focuses on the optimization of container shipping network and its operations under changing cargo demand and freight rates. The problem is formulated as a mixed integer non-linear programming problem (MINP with an objective of maximizing the average unit ship-slot profit at three stages using analytical methodology. The issues such as empty container repositioning, ship-slot allocating, ship sizing, and container configuration are simultaneously considered based on a series of the matrices of demand for a year. To solve the model, a bi-level genetic algorithm based method is proposed. Finally, numerical experiments are provided to illustrate the validity of the proposed model and algorithms. The obtained results show that the suggested model can provide a more realistic solution to the issues on the basis of changing demand and freight rates and arrange a more effective approach to the optimization of container shipping network structures and operations than does the model based on the average demand.

A statistical experimental design approach to evaluate the influence of various penetration enhancers on transdermal drug delivery of buprenorphine

Directory of Open Access Journals (Sweden)

S.Mojtaba Taghizadeh

2015-03-01

Full Text Available A series of drug-in-adhesive transdermal drug delivery systems (patch with different chemical penetration enhancers were designed to deliver drug through the skin as a site of application. The objective of our effort was to study the influence of various chemical penetration enhancers on skin permeation rate and adhesion properties of a transdermal drug delivery system using Box–Behnken experimental design. The response surface methodology based on a three-level, three-variable Box–Behnken design was used to evaluate the interactive effects on dependent variables including, the rate of skin permeation and adhesion properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol, and Tween 80 were used as penetration enhancers (patch formulations, containing 0–8% of each chemical penetration enhancer. Buprenorphine was used as a model penetrant drug. The results showed that incorporation of 20% chemical penetration enhancer into the mixture led to maximum skin permeation flux of buprenorphine from abdominal rat skin while the adhesion properties decreased. Also that skin flux in presence of levulinic acid (1.594 μg/cm2 h was higher than Tween 80 (1.473 μg/cm2 h and lauryl alcohol (0.843 μg/cm2 h, and in mixing these enhancers together, an additional effect was observed. Moreover, it was found that each enhancer increased the tack value, while levulinic acid and lauryl alcohol improved the peel strength but Tween 80 reduced it. These findings indicated that the best chemical skin penetration enhancer for buprenorphine patch was levulinic acid. Among the designed formulations, the one which contained 12% (wt/wt enhancers exhibited the highest efficiency.

A statistical experimental design approach to evaluate the influence of various penetration enhancers on transdermal drug delivery of buprenorphine.

Science.gov (United States)

Taghizadeh, S Mojtaba; Moghimi-Ardakani, Ali; Mohamadnia, Fatemeh

2015-03-01

A series of drug-in-adhesive transdermal drug delivery systems (patch) with different chemical penetration enhancers were designed to deliver drug through the skin as a site of application. The objective of our effort was to study the influence of various chemical penetration enhancers on skin permeation rate and adhesion properties of a transdermal drug delivery system using Box-Behnken experimental design. The response surface methodology based on a three-level, three-variable Box-Behnken design was used to evaluate the interactive effects on dependent variables including, the rate of skin permeation and adhesion properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol, and Tween 80 were used as penetration enhancers (patch formulations, containing 0-8% of each chemical penetration enhancer). Buprenorphine was used as a model penetrant drug. The results showed that incorporation of 20% chemical penetration enhancer into the mixture led to maximum skin permeation flux of buprenorphine from abdominal rat skin while the adhesion properties decreased. Also that skin flux in presence of levulinic acid (1.594 μg/cm(2) h) was higher than Tween 80 (1.473 μg/cm(2) h) and lauryl alcohol (0.843 μg/cm(2) h), and in mixing these enhancers together, an additional effect was observed. Moreover, it was found that each enhancer increased the tack value, while levulinic acid and lauryl alcohol improved the peel strength but Tween 80 reduced it. These findings indicated that the best chemical skin penetration enhancer for buprenorphine patch was levulinic acid. Among the designed formulations, the one which contained 12% (wt/wt) enhancers exhibited the highest efficiency.

Solar + Storage Synergies for Managing Commercial-Customer Demand Charges

Energy Technology Data Exchange (ETDEWEB)

Gagnon, P. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Govindarajan, A. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Bird, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Barbose, G. L. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Darghouth, N. R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mills, A. D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2017-10-18

Demand charges, which are based on a customer’s maximum demand in kilowatts (kW), are a common element of electricity rate structures for commercial customers. Customer-sited solar photovoltaic (PV) systems can potentially reduce demand charges, but the level of savings is difficult to predict, given variations in demand charge designs, customer loads, and PV generation profiles. Lawrence Berkeley National Laboratory (Berkeley Lab) and the National Renewable Energy Laboratory (NREL) are collaborating on a series of studies to understand how solar PV can impact demand charges. Prior studies in the series examined demand charge reductions from solar on a stand-alone basis for residential and commercial customers. Those earlier analyses found that solar, alone, has limited ability to reduce demand charges depending on the specific design of the demand charge and on the shape of the customer’s load profile. This latest analysis estimates demand charge savings from solar in commercial buildings when co-deployed with behind-the-meter storage, highlighting the complementary roles of the two technologies. The analysis is based on simulated loads, solar generation, and storage dispatch across a wide variety of building types, locations, system configurations, and demand charge designs.

A high turndown, ultra low emission low swirl burner for natural gas, on-demand water heaters

Energy Technology Data Exchange (ETDEWEB)

Rapp, Vi H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cheng, Robert K. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Therkelsen, Peter L. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2017-06-13

Previous research has shown that on-demand water heaters are, on average, approximately 37% more efficient than storage water heaters. However, approximately 98% of water heaters in the U.S. use storage water heaters while the remaining 2% are on-demand. A major market barrier to deployment of on-demand water heaters is their high retail cost, which is due in part to their reliance on multi-stage burner banks that require complex electronic controls. This project aims to research and develop a cost-effective, efficient, ultra-low emission burner for next generation natural gas on-demand water heaters in residential and commercial buildings. To meet these requirements, researchers at the Lawrence Berkeley National Laboratory (LBNL) are adapting and testing the low-swirl burner (LSB) technology for commercially available on-demand water heaters. In this report, a low-swirl burner is researched, developed, and evaluated to meet targeted on-demand water heater performance metrics. Performance metrics for a new LSB design are identified by characterizing performance of current on-demand water heaters using published literature and technical specifications, and through experimental evaluations that measure fuel consumption and emissions output over a range of operating conditions. Next, target metrics and design criteria for the LSB are used to create six 3D printed prototypes for preliminary investigations. Prototype designs that proved the most promising were fabricated out of metal and tested further to evaluate the LSB’s full performance potential. After conducting a full performance evaluation on two designs, we found that one LSB design is capable of meeting or exceeding almost all the target performance metrics for on-demand water heaters. Specifically, this LSB demonstrated flame stability when operating from 4.07 kBTU/hr up to 204 kBTU/hr (50:1 turndown), compliance with SCAQMD Rule 1146.2 (14 ng/J or 20 ppm NOX @ 3% O2), and lower CO emissions than state

Design of a tripartite network for the prediction of drug targets

Science.gov (United States)

Kunimoto, Ryo; Bajorath, Jürgen

2018-02-01

Drug-target networks have aided in many target prediction studies aiming at drug repurposing or the analysis of side effects. Conventional drug-target networks are bipartite. They contain two different types of nodes representing drugs and targets, respectively, and edges indicating pairwise drug-target interactions. In this work, we introduce a tripartite network consisting of drugs, other bioactive compounds, and targets from different sources. On the basis of analog relationships captured in the network and so-called neighbor targets of drugs, new drug targets can be inferred. The tripartite network was found to have a stable structure and simulated network growth was accompanied by a steady increase in assortativity, reflecting increasing correlation between degrees of connected nodes leading to even network connectivity. Local drug environments in the tripartite network typically contained neighbor targets and revealed interesting drug-compound-target relationships for further analysis. Candidate targets were prioritized. The tripartite network design extends standard drug-target networks and provides additional opportunities for drug target prediction.

Dynamic modelling of a PV pumping system with special consideration on water demand

International Nuclear Information System (INIS)

Campana, Pietro Elia; Li, Hailong; Yan, Jinyue

2013-01-01

Highlights: ► Evaluation of water demand and solar energy is essential for PV pumping system. ► The design for a PV water pumping system has been optimized based on dynamic simulations. ► It is important to conduct dynamic simulations to check the matching between water demand and water supply. ► AC pump driven by the fixed PV array is the most cost-effective solution. - Abstract: The exploitation of solar energy in remote areas through photovoltaic (PV) systems is an attractive solution for water pumping for irrigation systems. The design of a photovoltaic water pumping system (PVWPS) strictly depends on the estimation of the crop water requirements and land use since the water demand varies during the watering season and the solar irradiation changes time by time. It is of significance to conduct dynamic simulations in order to achieve the successful and optimal design. The aim of this paper is to develop a dynamic modelling tool for the design of a of photovoltaic water pumping system by combining the models of the water demand, the solar PV power and the pumping system, which can be used to validate the design procedure in terms of matching between water demand and water supply. Both alternate current (AC) and direct current (DC) pumps and both fixed and two-axis tracking PV array were analyzed. The tool has been applied in a case study. Results show that it has the ability to do rapid design and optimization of PV water pumping system by reducing the power peak and selecting the proper devices from both technical and economic viewpoints. Among the different alternatives considered in this study, the AC fixed system represented the best cost effective solution

Improving clinical drug development regulatory procedures for anticonvulsants

Directory of Open Access Journals (Sweden)

Janković Slobodan

2015-01-01

Full Text Available Background: Clinical development of antiepileptic drugs is demanding due to complex character of the disorder and to diversity of its forms and etiologies. Objective: The aim of this review was to suggest improvements in regulatory procedures for clinical development of antiepileptic drugs. Methods: The following databases of scientific articles were searched: MEDLINE, SCOPUS and SCINDEKS. In total 558 publications were retrieved. The types of articles selected were reviews, reports on clinical trials and letters to the Editor. Results: There are several changes of regulatory documents necessary for improving process of clinical development of antiepileptic drugs: preference of parallel groups design for add-on trials should be explicit; the noninferiority design for monotherapy clinical trials should be acceptable; restrictive formulations when trials of antiepileptic drugs in children are in question should be avoided; requirements in regard to the efficacy measures should be harmonized among the regulatory bodies; proactive attitude towards discovery of adverse events; and precise requirements for clinical trials specifically designed to prove anti-epileptogenic effects should be made clear. Conclusion: Current regulatory documents are incomplete in many aspects; an international effort to improve and harmonize guidelines for clinical development of antiepileptic drugs is necessary for improvement of this process.

Grid Based Technologies for in silico Screening and Drug Design.

Science.gov (United States)

Potemkin, Vladimir; Grishina, Maria

2018-03-08

Various techniques for rational drug design are presented in the paper. The methods are based on a substitution of antipharmacophore atoms of the molecules of training dataset by new atoms and/or group of atoms increasing the atomic bioactivity increments obtained at a SAR study. Furthermore, a design methodology based on the genetic algorithm DesPot for discrete optimization and generation of new drug candidate structures is described. Additionally, wide spectra of SAR approaches (3D/4D QSAR interior and exterior-based methods - BiS, CiS, ConGO, CoMIn, high-quality docking method - ReDock) using MERA force field and/or AlteQ quantum chemical method for correct prognosis of bioactivity and bioactive probability is described. The design methods are implemented now at www.chemosophia.com web-site for online computational services. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan.

Science.gov (United States)

Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

2011-06-01

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

Science.gov (United States)

Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

2011-06-01

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

Influence of drug colour on perceived drug effects and efficacy.

Science.gov (United States)

Tao, Da; Wang, Tieyan; Wang, Tieshan; Qu, Xingda

2018-02-01

A drug's physical characteristics, such as colour, could be factors influencing its therapeutic effects. It is not well understood whether people's expectations on drug effects and efficacy are affected by colour, especially among Chinese population. This study was conducted to examine people's expectations on drug effects and efficacy on the basis of drug colour, and to reveal possible gender differences in colour-related drug expectations. Participants (n = 224) were asked to classify seven single-coloured and six two-coloured capsules into one of four categories of drug effects, and to indicate the strength of drug efficacy. It is found that all the coloured capsules yielded non-chance distributions in classifications of drug effects, with six single-coloured and four two-coloured capsules associated with specific drug effects. Colour also conveyed differential strengths of drug efficacy in general and in relation to specific drug effects. There were gender differences in drug expectations for some colours and colour combinations. Practitioner Summary: Drug colour was found to have impacts on perceived drug effects and efficacy. The findings from the present study can be used by ergonomics practitioners to design appropriate drug colours in support of drug differentiation, therapeutic effects and medication adherence.

75 FR 52780 - Designation of Nine Counties as High Intensity Drug Trafficking Areas

Science.gov (United States)

2010-08-27

... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Nine Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated nine additional counties as High Drug Trafficking Areas pursuant to...

75 FR 21368 - Designation of Five Counties as High Intensity Drug Trafficking Areas

Science.gov (United States)

2010-04-23

... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Five Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated five additional counties as High Drug Trafficking Areas pursuant to...

Which electricity market design to encourage the development of demand response?

OpenAIRE

Vincent Rious, Fabien Roques and Yannick Perez

2012-01-01

Demand response is a cornerstone problem in electricity markets under climate change constraint. Most liberalized electricity markets have a poor track record at encouraging the deployment of smart meters and the development of demand response. In Europe, different models are considered for demand response, from a development under a regulated regime to a development under competitive perspectives. In this paper, focusing on demand response and smart metering for mid-size and small consumers,...

Which electricity market design to encourage the development of demand response?

OpenAIRE

Rious , Vincent; Perez , Yannick; Roques , Fabien

2015-01-01

International audience; Demand response is a cornerstone problem in electricity markets under climate change constraints. Most liberalized electricity markets have a poor track record at encouraging the deployment of smart meters and the development of demand response. In Europe, different models are considered for demand response, from a development under a regulated regime to a development under competitive perspectives. In this paper focusing on demand response and smart metering for mid-­...

Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety.

Science.gov (United States)

Meanwell, Nicholas A

2011-09-19

The development of small molecule drug candidates from the discovery phase to a marketed product continues to be a challenging enterprise with very low success rates that have fostered the perception of poor productivity by the pharmaceutical industry. Although there have been significant advances in preclinical profiling that have improved compound triaging and altered the underlying reasons for compound attrition, the failure rates have not appreciably changed. As part of an effort to more deeply understand the reasons for candidate failure, there has been considerable interest in analyzing the physicochemical properties of marketed drugs for the purpose of comparing with drugs in discovery and development as a means capturing recent trends in drug design. The scenario that has emerged is one in which contemporary drug discovery is thought to be focused too heavily on advancing candidates with profiles that are most easily satisfied by molecules with increased molecular weight and higher overall lipophilicity. The preponderance of molecules expressing these properties is frequently a function of increased aromatic ring count when compared with that of the drugs launched in the latter half of the 20th century and may reflect a preoccupation with maximizing target affinity rather than taking a more holistic approach to drug design. These attributes not only present challenges for formulation and absorption but also may influence the manifestation of toxicity during development. By providing some definition around the optimal physicochemical properties associated with marketed drugs, guidelines for drug design have been developed that are based largely on calculated parameters and which may readily be applied by medicinal chemists as an aid to understanding candidate quality. The physicochemical properties of a molecule that are consistent with the potential for good oral absorption were initially defined by Lipinski, with additional insights allowing further

HIV protease drug resistance and its impact on inhibitor design.

Science.gov (United States)

Ala, P J; Rodgers, J D; Chang, C H

1999-07-01

The primary cause of resistance to the currently available HIV protease inhibitors is the accumulation of multiple mutations in the viral protease. So far more than 20 substitutions have been observed in the active site, dimer interface, surface loops and flaps of the homodimer. While many mutations reduce the protease's affinity for inhibitors, others appear to enhance its catalytic efficiency. This high degree of genetic flexibility has made the protease an elusive drug target. The design of the next generation of HIV protease inhibitors will be discussed in light of the current structural information.

Demand-Driven Success: Designing Your PDA Experiment

OpenAIRE

Hillen, Charles; Johnson-Grau, Glenn

2012-01-01

Initiating demand-driving acquisition is daunting. Implications for developing a sustainable budget model, choosing a vendor, controlling metadata, monitoring purchases and developing invoice workflows are significant areas of concern that require determinative planning. From mid-February through August 2011, Loyola Marymount University conducted a pilot using demand-driven acquisition; the result of this successful experiment was the library’s decision to fully integrate this purchasing mode...

The design of drugs for HIV and HCV.

Science.gov (United States)

De Clercq, Erik

2007-12-01

Since the discovery of the human immunodeficiency virus (HIV) in 1983, dramatic progress has been made in the development of novel antiviral drugs. The HIV epidemic fuelled the development of new antiviral drug classes, which are now combined to provide highly active antiretroviral therapies. The need for the treatment of hepatitis C virus (HCV), which was discovered in 1989, has also provided considerable impetus for the development of new classes of antiviral drugs, and future treatment strategies for chronic HCV might involve combination regimens that are analogous to those currently used for HIV. By considering the drug targets in the different stages of the life cycle of these two viruses, this article presents aspects of the history, medicinal chemistry and mechanisms of action of approved and investigational drugs for HIV and HCV, and highlights general lessons learned from anti-HIV-drug design that could be applied to HCV.

Supply and demand: application of Lean Six Sigma methods to improve drug round efficiency and release nursing time.

Science.gov (United States)

Kieran, Maríosa; Cleary, Mary; De Brún, Aoife; Igoe, Aileen

2017-10-01

To improve efficiency, reduce interruptions and reduce the time taken to complete oral drug rounds. Lean Six Sigma methods were applied to improve drug round efficiency using a pre- and post-intervention design. A 20-bed orthopaedic ward in a large teaching hospital in Ireland. Pharmacy, nursing and quality improvement staff. A multifaceted intervention was designed which included changes in processes related to drug trolley organization and drug supply planning. A communications campaign aimed at reducing interruptions during nurse-led during rounds was also developed and implemented. Average number of interruptions, average drug round time and variation in time taken to complete drug round. At baseline, the oral drug round took an average of 125 min. Following application of Lean Six Sigma methods, the average drug round time decreased by 51 min. The average number of interruptions per drug round reduced from an average of 12 at baseline to 11 following intervention, with a 75% reduction in drug supply interruptions. Lean Six Sigma methodology was successfully employed to reduce interruptions and to reduce time taken to complete the oral drug round. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Exploring G Protein-Coupled Receptors (GPCRs) Ligand Space via Cheminformatics Approaches: Impact on Rational Drug Design

Science.gov (United States)

Basith, Shaherin; Cui, Minghua; Macalino, Stephani J. Y.; Park, Jongmi; Clavio, Nina A. B.; Kang, Soosung; Choi, Sun

2018-01-01

The primary goal of rational drug discovery is the identification of selective ligands which act on single or multiple drug targets to achieve the desired clinical outcome through the exploration of total chemical space. To identify such desired compounds, computational approaches are necessary in predicting their drug-like properties. G Protein-Coupled Receptors (GPCRs) represent one of the largest and most important integral membrane protein families. These receptors serve as increasingly attractive drug targets due to their relevance in the treatment of various diseases, such as inflammatory disorders, metabolic imbalances, cardiac disorders, cancer, monogenic disorders, etc. In the last decade, multitudes of three-dimensional (3D) structures were solved for diverse GPCRs, thus referring to this period as the “golden age for GPCR structural biology.” Moreover, accumulation of data about the chemical properties of GPCR ligands has garnered much interest toward the exploration of GPCR chemical space. Due to the steady increase in the structural, ligand, and functional data of GPCRs, several cheminformatics approaches have been implemented in its drug discovery pipeline. In this review, we mainly focus on the cheminformatics-based paradigms in GPCR drug discovery. We provide a comprehensive view on the ligand– and structure-based cheminformatics approaches which are best illustrated via GPCR case studies. Furthermore, an appropriate combination of ligand-based knowledge with structure-based ones, i.e., integrated approach, which is emerging as a promising strategy for cheminformatics-based GPCR drug design is also discussed. PMID:29593527

[Drug advertising--users want information. Report of telephone survey conducted by North-Rhine Westphalia Public Health Service on the topic of drug advertising and drug information for users].

Science.gov (United States)

Puteanus, U

2000-10-01

In Germany, drug advertising of non-prescription drugs is a controversial subject. On the one hand, consumer organisations plead for placing a ban on advertising or at least to offer a detailed description of medical risks in respect of protection. On the other hand, the pharmaceutical industry is keen on liberalizing the specific advertising law for drugs. A representative telephone survey among the population of North Rhine-Westphalia was conducted in April and May 1999. It showed consumer interest in advertising, the value of information on risks, the institution with maximum credibility in drug information for consumers, the importance of the now obligatory sentence after every advertisement: Regarding risks and side effects read the leaflet in the package and ask your physician or pharmacist, and to what extend the consumer would take advice from independent experts over the telephone about drugs. It was found that, in particular women, about 30% are occasionally interested in advertising, younger people are more open-minded about advertising than older people; and that doctors and pharmacists have the most credibility and are consulted for further information. It was also found that more than 80% of the population demanded precise information on the side effects of drugs. One-third of the consumers declared that the obligatory sentence (see above) led to greater demand for information from doctors or to read attentively the instruction leaflet. Nevertheless, there is a need for more information from more than half of the consumers, who would take advantage of an independent advice centre if this should exist.

21 CFR 516.36 - Insufficient quantities of MUMS-designated drugs.

Science.gov (United States)

2010-04-01

... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.36 Insufficient quantities of... the 7-year period of exclusive marketing rights. (b) If, within the time that FDA specifies, the...

Effectiveness of Culturally Appropriate Initiative on Drug-Related Harm Reduction for Sex Workers on the Thai/Malaysian Border.

Science.gov (United States)

Nunun, Worapol; Kanato, Manop

2015-07-01

Drug use can harm to sex workers. Abstinence intervention, however, may not be appropriate since drug use fosters their career performance. The objective was to develop the culturally appropriate model for sex workers participation on drug demand reduction at the Thailand/Malaysian border This study was a pre-post quasi-experimental design. Tripartite participation was used to develop the model aiming to reduce harm regarding drug use. The study carried out during June 2010-May 2011. Data were collected from 150 key informant interviews, 56 focus group discussions, 22 participant observations in various situations, and numerous related materials. Descriptive statistics, survival analysis and 95% confidence interval were utilizedfor quantitative data. Qualitative data were analyzed by content analysis. Drug related harm reduction was evaluated at two-week time along implementation period of 12 months. 89.5% of all sessions introduced could decrease drug related harm. Of all sex workers participated in the study, intended to treat analysis showed 86.9% success rate (95% CI; 77.1, 96.7). Of these, 32.6% became abstinence, 39.1% reduced most of drug related harm. 13.0% reduced partial drug related harm either lessfrequency, less quantity, less concentration, decrease types of drugs/switch to safe drugs or safer method of administration. 2.2% was infancy stage, which needed further support. Key success ofthe model was tripartite participation. With active leaders and strong support, sex workers were continually motivated to reduce harm regarding drug use.

Estimation of demand function on natural gas and study of demand analysis

Energy Technology Data Exchange (ETDEWEB)

Kim, Y.D. [Korea Energy Economics Institute, Euiwang (Korea, Republic of)

1998-04-01

Demand Function is estimated with several methods about the demand on natural gas, and analyzed per usage. Since the demand on natural gas, which has big share of heating use, has a close relationship with temperature, the inter-season trend of price and income elasticity is estimated considering temperature and economic formation. Per usage response of natural gas demand on the changes of price and income is also estimated. It was estimated that the response of gas demand on the changes of price and income occurs by the change of number of users in long term. In case of the response of unit consumption, only industrial use shows long-term response to price. Since gas price barely responds to the change of exchange rate, it seems to express the price-making mechanism that does not reflect timely the import condition such as exchange rate, etc. 16 refs., 12 figs., 13 tabs.

Demand-Side Flexibility for Energy Transitions: Policy Recommendations for Developing Demand Response

OpenAIRE

Nursimulu, Anjali; Florin, Marie-Valentine; Vuille, François

2016-01-01

As a follow-up to IRGC's report on demand-side flexibility for energy transitions, this Policy Brief highlights that increasing flexibility in power systems is needed to accommodate higher shares of non-controllable and intermittent renewable generation, and that this requires changes to the market design and regulatory framework, to facilitate the development and deployment of appropriate technologies and market-based instruments (e.g. taxes and subsidies). The Policy Brief focuses on demand...

Income and the use of prescription drugs for near retirement individuals

DEFF Research Database (Denmark)

Leth-Petersen, Søren; Skipper, Niels

Understanding how demand for prescription drugs responds to changes in income is important for assessing the welfare consequences of reforms affecting income. This becomes more imminent as age progresses, because the use of prescription drugs and the associated budgetary burden increases dramatic......Understanding how demand for prescription drugs responds to changes in income is important for assessing the welfare consequences of reforms affecting income. This becomes more imminent as age progresses, because the use of prescription drugs and the associated budgetary burden increases...... dramatically from about age 55. In this paper we estimate how demand for prescription drugs varies with income for a sample of near retirement individuals. Estimating the prescription drug demand response to income changes is complicated because an important explanatory variable, the health capital......, is unobserved, and because demand is potentially dynamic, for example because some drugs are habitual. The analysis is based on a novel panel data set with information about purchase of prescription drug demand for a very large number of Danish individuals over the period 1995-2003. Our preferred model...

Designing a capacitated multi-configuration logistics network under disturbances and parameter uncertainty: a real-world case of a drug supply chain

Science.gov (United States)

Shishebori, Davood; Babadi, Abolghasem Yousefi

2018-03-01

This study investigates the reliable multi-configuration capacitated logistics network design problem (RMCLNDP) under system disturbances, which relates to locating facilities, establishing transportation links, and also allocating their limited capacities to the customers conducive to provide their demand on the minimum expected total cost (including locating costs, link constructing costs, and also expected costs in normal and disturbance conditions). In addition, two types of risks are considered; (I) uncertain environment, (II) system disturbances. A two-level mathematical model is proposed for formulating of the mentioned problem. Also, because of the uncertain parameters of the model, an efficacious possibilistic robust optimization approach is utilized. To evaluate the model, a drug supply chain design (SCN) is studied. Finally, an extensive sensitivity analysis was done on the critical parameters. The obtained results show that the efficiency of the proposed approach is suitable and is worthwhile for analyzing the real practical problems.

Optimization and design of ibuprofen-loaded nanostructured lipid carriers using a hybrid-design approach for ocular drug delivery

Science.gov (United States)

Rathod, Vishal

The objective of the present project was to develop the Ibuprofen-loaded Nanostructured Lipid Carrier (IBU-NLCs) for topical ocular delivery based on substantial pre-formulation screening of the components and understanding the interplay between the formulation and process variables. The BCS Class II drug: Ibuprofen was selected as the model drug for the current study. IBU-NLCs were prepared by melt emulsification and ultrasonication technique. Extensive pre-formulation studies were performed to screen the lipid components (solid and liquid) based on drug's solubility and affinity as well as components compatibility. The results from DSC & XRD assisted in selecting the most suitable ratio to be utilized for future studies. DynasanRTM 114 was selected as the solid lipid & MiglyolRTM 840 was selected as the liquid lipid based on preliminary lipid screening. The ratio of 6:4 was predicted to be the best based on its crystallinity index and the thermal events. As there are many variables involved for further optimization of the formulation, a single design approach is not always adequate. A hybrid-design approach was applied by employing the Plackett Burman design (PBD) for preliminary screening of 7 critical variables, followed by Box-Behnken design (BBD), a sub-type of response surface methodology (RSM) design using 2 relatively significant variables from the former design and incorporating Surfactant/Co-surfactant ratio as the third variable. Comparatively, KolliphorRTM HS15 demonstrated lower Mean Particle Size (PS) & Polydispersity Index (PDI) and KolliphorRTM P188 resulted in Zeta Potential (ZP) ibuprofen thereafter over several hours. These values also confirm that the production method, and all other selected variables, effectively promoted the incorporation of ibuprofen in NLC. Quality by Design (QbD) approach was successfully implemented in developing a robust ophthalmic formulation with superior physicochemical and morphometric properties. NLCs as the

Screening applications in drug discovery based on microfluidic technology

Science.gov (United States)

Eribol, P.; Uguz, A. K.; Ulgen, K. O.

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

Screening applications in drug discovery based on microfluidic technology.

Science.gov (United States)

Eribol, P; Uguz, A K; Ulgen, K O

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

Antiretroviral drug expenditure, pricing and judicial demand: an analysis of federal procurement data in Brazil from 2004–2011

Science.gov (United States)

2014-01-01

Background Previous studies have described expenditures for antiretroviral (ARV) medicines in Brazil through 2005. While prior studies examined overall expenditures, they have not have analyzed drug procurement data in order to describe the role of court litigation on access and pricing. Methods ARV drug procurement from private sector sources for the years 2004–2011 was obtained through the general procurement database of the Brazilian Federal Government (SIASG). Procurement was measured in Defined Daily Doses (DDD) per 1000 persons-under-treatment per day. Expenditures and price per DDD were calculated and expressed in U.S. Dollars. Justifications for ARV purchases were examined in order to determine the relationship between health litigation and incorporation into Brazil’s national treatment guidelines. Results Drug procurement of ARVs from private sources underwent marked expansion in 2005, peaked in 2009, and stabilized to 2008 levels by 2011. Expenditures followed procurement curves. Medications which were procured for the first time after 2007 cost more than medicines which were introduced before 2007. Judicial actions initially resulted in purchases of newer medications for a select number of patients in Brazil but ultimately expanded availability to a larger population through incorporation into the national treatment guidelines. Conclusions Drug procurement and expenditures for ARVs in Brazil varied between 2004–2011. The procurement of some drugs from the private sector ceased after public manufacturers started producing them locally. Judicial demand has resulted in the incorporation of newer drugs into the national treatment guidelines. In order for the AIDS treatment program to remain sustainable, efforts should be pursued to reduce prices through generic drugs, price negotiation and other public health flexibilities such as compulsory licensing. PMID:24735589

Demand response impacts on off-grid hybrid photovoltaic-diesel generator microgrids

Directory of Open Access Journals (Sweden)

Aaron St. Leger

2015-08-01

Full Text Available Hybrid microgrids consisting of diesel generator set(s and converter based power sources, such as solar photovoltaic or wind sources, offer an alternative to generator based off-grid power systems. The hybrid approach has been shown to be economical in many off-grid applications and can result in reduced generator operation, fuel requirements, and maintenance. However, the intermittent nature of demand and renewable energy sources typically require energy storage, such as batteries, to properly operate the hybrid microgrid. These batteries increase the system cost, require proper operation and maintenance, and have been shown to be unreliable in case studies on hybrid microgrids. This work examines the impacts of leveraging demand response in a hybrid microgrid in lieu of energy storage. The study is performed by simulating two different hybrid diesel generator—PV microgrid topologies, one with a single diesel generator and one with multiple paralleled diesel generators, for a small residential neighborhood with varying levels of demand response. Various system designs are considered and the optimal design, based on cost of energy, is presented for each level of demand response. The solar resources, performance of solar PV source, performance of diesel generators, costs of system components, maintenance, and operation are modeled and simulated at a time interval of ten minutes over a twenty-five year period for both microgrid topologies. Results are quantified through cost of energy, diesel fuel requirements, and utilization of the energy sources under varying levels of demand response. The results indicate that a moderate level of demand response can have significant positive impacts to the operation of hybrid microgrids through reduced energy cost, fuel consumption, and increased utilization of PV sources.

Global impacts of energy demand on the freshwater resources of nations.

Science.gov (United States)

Holland, Robert Alan; Scott, Kate A; Flörke, Martina; Brown, Gareth; Ewers, Robert M; Farmer, Elizabeth; Kapos, Valerie; Muggeridge, Ann; Scharlemann, Jörn P W; Taylor, Gail; Barrett, John; Eigenbrod, Felix

2015-12-01

The growing geographic disconnect between consumption of goods, the extraction and processing of resources, and the environmental impacts associated with production activities makes it crucial to factor global trade into sustainability assessments. Using an empirically validated environmentally extended global trade model, we examine the relationship between two key resources underpinning economies and human well--being-energy and freshwater. A comparison of three energy sectors (petroleum, gas, and electricity) reveals that freshwater consumption associated with gas and electricity production is largely confined within the territorial boundaries where demand originates. This finding contrasts with petroleum, which exhibits a varying ratio of territorial to international freshwater consumption, depending on the origin of demand. For example, although the United States and China have similar demand associated with the petroleum sector, international freshwater consumption is three times higher for the former than the latter. Based on mapping patterns of freshwater consumption associated with energy sectors at subnational scales, our analysis also reveals concordance between pressure on freshwater resources associated with energy production and freshwater scarcity in a number of river basins globally. These energy-driven pressures on freshwater resources in areas distant from the origin of energy demand complicate the design of policy to ensure security of fresh water and energy supply. Although much of the debate around energy is focused on greenhouse gas emissions, our findings highlight the need to consider the full range of consequences of energy production when designing policy.

Temperature Effect on Energy Demand

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Duk [Korea Energy Economics Institute, Euiwang (Korea)

1999-03-01

We provide various estimates of temperature effect for accommodating seasonality in energy demand, particularly natural gas demand. We exploit temperature response and monthly temperature distribution to estimate the temperature effect on natural gas demand. Both local and global smoothed temperature responses are estimated from empirical relationship between hourly temperature and hourly energy consumption data during the sample period (1990 - 1996). Monthly temperature distribution estimates are obtained by kernel density estimation from temperature dispersion within a month. We integrate temperature response and monthly temperature density over all the temperatures in the sample period to estimate temperature effect on energy demand. Then, estimates of temperature effect are compared between global and local smoothing methods. (author). 15 refs., 14 figs., 2 tabs.

Effects of two hospital bed design features on physical demands and usability during brake engagement and patient transportation: a repeated measures experimental study.

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Kim, Sunwook; Barker, Linsey M; Jia, Bochen; Agnew, Michael J; Nussbaum, Maury A

2009-03-01

Work-related musculoskeletal disorders (WMSDs) are prevalent among healthcare workers worldwide. While existing research has focused on patient-handling techniques during activities which require direct patient contact (e.g., patient transfer), nursing tasks also involve other patient-handling activities, such as engaging bed brakes and transporting patients in beds, which could render healthcare workers at risk of developing WMSDs. Effectiveness of hospital bed design features (brake pedal location and steering-assistance) was evaluated in terms of physical demands and usability during brake engagement and patient transportation tasks. Two laboratory-based studies were conducted. In simulated brake engagement tasks, three brake pedal locations (head-end vs. foot-end vs. side of a bed) and two hands conditions (hands-free vs. hands-occupied) were manipulated. Additionally, both in-room and corridor patient transportation tasks were simulated, in which activation of steering-assistance features (5th wheel and/or front wheel caster lock) and two patient masses were manipulated. Nine novice participants were recruited from the local student population and community for each study. During brake engagement, trunk flexion angle, task completion time, and questionnaires were used to quantify postural comfort and usability. For patient transportation, dependent measures were hand forces and questionnaire responses. Brake pedal locations and steering-assistance features in hospital beds had significant effects on physical demands and usability during brake engagement and patient transportation tasks. Specifically, a brake pedal at the head-end of a bed increased trunk flexion by 74-224% and completion time by 53-74%, compared to other pedal locations. Participants reported greater overall perceived difficulty and less postural comfort with the brake pedal at the head-end. During in-room transportation, participants generally reported "Neither Low nor High" physical demands

Demand Response Programs Design and Use Considering Intensive Penetration of Distributed Generation

Directory of Open Access Journals (Sweden)

Pedro Faria

2015-06-01

Full Text Available Further improvements in demand response programs implementation are needed in order to take full advantage of this resource, namely for the participation in energy and reserve market products, requiring adequate aggregation and remuneration of small size resources. The present paper focuses on SPIDER, a demand response simulation that has been improved in order to simulate demand response, including realistic power system simulation. For illustration of the simulator’s capabilities, the present paper is proposes a methodology focusing on the aggregation of consumers and generators, providing adequate tolls for the demand response program’s adoption by evolved players. The methodology proposed in the present paper focuses on a Virtual Power Player that manages and aggregates the available demand response and distributed generation resources in order to satisfy the required electrical energy demand and reserve. The aggregation of resources is addressed by the use of clustering algorithms, and operation costs for the VPP are minimized. The presented case study is based on a set of 32 consumers and 66 distributed generation units, running on 180 distinct operation scenarios.

Versatile Chemical Derivatizations to Design Glycol Chitosan-Based Drug Carriers

Directory of Open Access Journals (Sweden)

Sung Eun Kim

2017-10-01

Full Text Available Glycol chitosan (GC and its derivatives have been extensively investigated as safe and effective drug delivery carriers because of their unique physiochemical and biological properties. The reactive functional groups such as the amine and hydroxyl groups on the GC backbone allow for easy chemical modification with various chemical compounds (e.g., hydrophobic molecules, crosslinkers, and acid-sensitive and labile molecules, and the versatility in chemical modifications enables production of a wide range of GC-based drug carriers. This review summarizes the versatile chemical modification methods that can be used to design GC-based drug carriers and describes their recent applications in disease therapy.

Computation-based virtual screening for designing novel antimalarial drugs by targeting falcipain-III: a structure-based drug designing approach.

Science.gov (United States)

Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna

2013-01-01

Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having

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

Science.gov (United States)

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

Three different applications of genetic algorithm (GA) search techniques on oil demand estimation

International Nuclear Information System (INIS)

Canyurt, Olcay Ersel; Oztuerk, Harun Kemal

2006-01-01

This present study develops three scenarios to analyze oil consumption and make future projections based on the Genetic algorithm (GA) notion, and examines the effect of the design parameters on the oil utilization values. The models developed in the non-linear form are applied to the oil demand of Turkey. The GA Oil Demand Estimation Model (GAODEM) is developed to estimate the future oil demand values based on Gross National Product (GNP), population, import, export, oil production, oil import and car, truck and bus sales figures. Among these models, the GA-PGOiTI model, which uses population, GNP, oil import, truck sales and import as design parameters/indicators, was found to provide the best fit solution with the observed data. It may be concluded that the proposed models can be used as alternative solution and estimation techniques for the future oil utilization values of any country

Systematic synergy modeling: understanding drug synergy from a systems biology perspective.

Science.gov (United States)

Chen, Di; Liu, Xi; Yang, Yiping; Yang, Hongjun; Lu, Peng

2015-09-16

Owing to drug synergy effects, drug combinations have become a new trend in combating complex diseases like cancer, HIV and cardiovascular diseases. However, conventional synergy quantification methods often depend on experimental dose-response data which are quite resource-demanding. In addition, these methods are unable to interpret the explicit synergy mechanism. In this review, we give representative examples of how systems biology modeling offers strategies toward better understanding of drug synergy, including the protein-protein interaction (PPI) network-based methods, pathway dynamic simulations, synergy network motif recognitions, integrative drug feature calculations, and "omic"-supported analyses. Although partially successful in drug synergy exploration and interpretation, more efforts should be put on a holistic understanding of drug-disease interactions, considering integrative pharmacology and toxicology factors. With a comprehensive and deep insight into the mechanism of drug synergy, systems biology opens a novel avenue for rational design of effective drug combinations.

Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

Directory of Open Access Journals (Sweden)

R Pignatello

2011-01-01

Full Text Available Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy.

Household social characteristics of the demand for alcoholic beverages among Spanish students.

Science.gov (United States)

Gil-Lacruz, Ana Isabel; Gil-Lacruz, Marta

2013-03-01

This paper studies how household social capital affects adolescents' demand for alcoholic drinks. To that end, we focus on a theoretical framework that combines elements from the Model of Rational Addiction and the Model of Social Economics. For the empirical framework, we use a simultaneous Type II Tobit model, with data drawn from the Spanish National Survey on Drug Use in the School Population (2000, 2002, and 2004). The sample is comprised of 12,627 students aged 17 years old. Our results confirm that parents' decisions about drinking are even more decisive in their children's behavior than socioeconomic variables, such as parents' educative levels or working status. Parental responsibilities go beyond the endowment of health and educational goods and services; so, these results suggest the importance of designing family-drug use prevention programs. The study's limitations are noted.

Non-residential water demand model validated with extensive measurements and surveys

NARCIS (Netherlands)

Pieterse-Quirijns, I.; Blokker, E.J.M.; van der Blom, E.C.; Vreeburg, J.H.G.

2013-01-01

Existing Dutch guidelines for the design of the drinking water and hot water system of nonresidential buildings are based on outdated assumptions on peak water demand or on unfounded assumptions on hot water demand. They generally overestimate peak demand values required for the design of an

A Budget Impact Model of Hemophilia Bypassing Agent Prophylaxis Relative to Recombinant Factor VIIa On-Demand.

Science.gov (United States)

Mehta, Darshan A; Oladapo, Abiola O; Epstein, Joshua D; Novack, Aaron R; Neufeld, Ellis J; Hay, Joel W

2016-02-01

Hemophilia patients use factor-clotting concentrates (factor VIII for hemophilia A and factor IX for hemophilia B) for improved blood clotting. These products are used to prevent or stop bleeding episodes. However, some hemophilia patients develop inhibitors (i.e., the patient's immune system develops antibodies against these factor concentrates). Hence, these patients do not respond well to the factor concentrates. A majority of hemophilia patients with inhibitors are managed on-demand with the following bypassing agents: recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC). The recently published U.S. registries Dosing Observational Study in Hemophilia (DOSE) and Hemostasis and Thrombosis Research Society (HTRS) reported higher rFVIIa on-demand use for bleed management than previously described. To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries. A literature-based cost model was developed assuming a base case on-demand annual bleed rate (ABR) of 28.7 per inhibitor patient, which was taken from a randomized phase 3 clinical trial. The doses for rFVIIa on-demand were taken from the median dose per bleed reported by the DOSE and HTRS registries. Model inputs for aPCC and rFVIIa prophylaxis (i.e., dosing and efficacy) were derived from respective randomized clinical trials. Cost analysis was from the U.S. payer perspective, and only direct drug costs were considered. The drug cost was based on the Medicare Part B 2014 average sale price (ASP). Two-way sensitivity and threshold analyses were performed by simultaneously varying on-demand ABR, prophylaxis efficacy, and unit drug cost. In addition to studying relative costs associated with on-demand and prophylaxis treatments, relative cost per bleeding episode avoided were also calculated for aPCC and rFVIIa prophylaxis treatments. The prophylaxis efficacy reported in the trials were used to

California DREAMing: The design of residential demand responsive technology with people in mind

Science.gov (United States)

Peffer, Therese Evelyn

Electrical utilities worldwide are exploring "demand response" programs to reduce electricity consumption during peak periods. Californian electrical utilities would like to pass the higher cost of peak demand to customers to offset costs, increase reliability, and reduce peak consumption. Variable pricing strategies require technology to communicate a dynamic price to customers and respond to that price. However, evidence from thermostat and energy display studies as well as research regarding energy-saving behaviors suggests that devices cannot effect residential demand response without the sanction and participation of people. This study developed several technologies to promote or enable residential demand response. First, along with a team of students and professors, I designed and tested the Demand Response Electrical Appliance Manager (DREAM). This wireless network of sensors, actuators, and controller with a user interface provides information to intelligently control a residential heating and cooling system and to inform people of their energy usage. We tested the system with computer simulation and in the laboratory and field. Secondly, as part of my contribution to the team, I evaluated machine-learning to predict a person's seasonal temperature preferences by analyzing existing data from office workers. The third part of the research involved developing an algorithm that generated temperature setpoints based on outdoor temperature. My study compared the simulated energy use using these setpoints to that using the setpoints of a programmable thermostat. Finally, I developed and tested a user interface for a thermostat and in-home energy display. This research tested the effects of both energy versus price information and the context of sponsorship on the behavior of subjects. I also surveyed subjects on the usefulness of various displays. The wireless network succeeded in providing detailed data to enable an intelligent controller and provide feedback to

Integrated Teaching of Structure-Based Drug Design and Biopharmaceutics: A Computer-Based Approach

Science.gov (United States)

Sutch, Brian T.; Romero, Rebecca M.; Neamati, Nouri; Haworth, Ian S.

2012-01-01

Rational drug design requires expertise in structural biology, medicinal chemistry, physiology, and related fields. In teaching structure-based drug design, it is important to develop an understanding of the need for early recognition of molecules with "drug-like" properties as a key component. That is, it is not merely sufficient to teach…

Continuous Drug Infusion for Diabetes Therapy: A Closed-Loop Control System Design

Directory of Open Access Journals (Sweden)

Jiming Chen

2008-03-01

Full Text Available While a typical way for diabetes therapy is discrete insulin infusion based on long-time interval measurement, in this paper, we design a closed-loop control system for continuous drug infusion to improve the traditional discrete methods and make diabetes therapy automatic in practice. By exploring the accumulative function of drug to insulin, a continuous injection model is proposed. Based on this model, proportional-integral-derivative (PID and fuzzy logic controllers are designed to tackle a control problem of the resulting highly nonlinear plant. Even with serious disturbance of glucose, such as nutrition absorption at meal time, the proposed scheme can perform well in simulation experiments.

A Prospective Method to Guide Small Molecule Drug Design

Science.gov (United States)

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)…

Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

Directory of Open Access Journals (Sweden)

Charles H. Williams

2011-04-01

Full Text Available In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design.

Effect of swimming suit design on the energy demands of swimming.

Science.gov (United States)

Starling, R D; Costill, D L; Trappe, T A; Jozsi, A C; Trappe, S W; Goodpaster, B H

1995-07-01

Eight competitive male swimmers completed a standardized 365.8 m (400 yd) freestyle swimming trial at a fixed pace (approximately 90% of maximal effort) while wearing a torso swim suit (TOR) or a standard racing suit (STD). Oxygen uptake (VO2), blood lactate, heart rate (HR), and distance per stroke (DPS) measurements were obtained. In addition, a video-computer system was used to collect velocity data during a prone underwater glide following a maximal leg push-off from the side of the pool while wearing the TOR and STD suits. These data were used to calculate the total distance covered during the glides. VO2 (3.76 +/- 0.16 vs 3.92 +/- 0.18 l.min-1) and lactate (8.08 +/- 0.53 vs, 9.66 +/- 0.66 mM) were significantly (P 0.05) between the TOR (170.1 +/- 5.1 b.min-1) and STD (173.5 +/- 5.7 b.min-1) trials. DPS was significantly greater during the TOR (2.70 +/- 0.066 m.stroke-1) versus STD (2.58 +/- 0.054 m.stroke-1) trial. A significantly greater total distance was covered during the prone glide while wearing the TOR (2.05 +/- 0.067 m) compared to the STD (2.00 +/- 0.080 m) suit. These findings demonstrate that a specially designed torso suit reduces the energy demand of swimming compared to a standard racing suit which may be due to a reduction in body drag.

America's Opioid Epidemic: Supply and Demand Considerations.

Science.gov (United States)

Clark, David J; Schumacher, Mark A

2017-11-01

America is in the midst of an opioid epidemic characterized by aggressive prescribing practices, highly prevalent opioid misuse, and rising rates of prescription and illicit opioid overdose-related deaths. Medical and lay public sentiment have become more cautious with respect to prescription opioid use in the past few years, but a comprehensive strategy to reduce our reliance on prescription opioids is lacking. Addressing this epidemic through reductions in unnecessary access to these drugs while implementing measures to reduce demand will be important components of any comprehensive solution. Key supply-side measures include avoiding overprescribing, reducing diversion, and discouraging misuse through changes in drug formulations. Important demand-side measures center around educating patients and clinicians regarding the pitfalls of opioid overuse and methods to avoid unnecessary exposure to these drugs. Anesthesiologists, by virtue of their expertise in the use of these drugs and their position in guiding opioid use around the time of surgery, have important roles to play in reducing patient exposure to opioids and providing education about appropriate use. Aside from the many immediate steps that can be taken, clinical and basic research directed at understanding the interaction between pain and opioid misuse is critical to identifying the optimal use of these powerful pain relievers in clinical practice.

Demand controlled ventilation for multi-family dwellings

DEFF Research Database (Denmark)

Mortensen, Dorthe Kragsig

for centrally balanced DCV systems with heat recovery. A design expected to fulfill this requirement was investigated in detail with regard to its electricity consumption by evaluating a control strategy that resets the static pressure set point at part load. The results showed that this control strategy can......The present thesis “Demand controlled ventilation for multi-family dwellings” constitutes the summary of a three year project period during which demand specification and system design of demand controlled ventilation for residential buildings were studied. Most standards and buildings codes...... can be reduced compared to a system with constant air flow. A literature study on indoor pollutants in homes, their sources and their impact on humans formed the basis for the demand specification. Emission of pollutants in residential buildings roughly fall into constantly emitted background sources...

Demand Response Design and Use Based on Network Locational Marginal Prices

DEFF Research Database (Denmark)

Morais, Hugo; Faria, Pedro; Vale, Zita

2014-01-01

Power systems have been experiencing huge changes mainly due to the substantial increase of distributed generation (DG) and the operation in competitive environments. Virtual Power Players (VPP) can aggregate several players, namely a diversity of energy resources, including distributed generation...... (DG) based on several technologies, electric storage systems (ESS) and demand response (DR). Energy resources management gains an increasing relevance in this competitive context. This makes the DR use more interesting and flexible, giving place to a wide range of new opportunities. This paper...... proposes a methodology to support VPPs in the DR programs’ management, considering all the existing energy resources (generation and storage units) and the distribution network. The proposed method is based on locational marginal prices (LMP) values. The evaluation of the impact of using DR specific...

Demand forecast model based on CRM

Science.gov (United States)

Cai, Yuancui; Chen, Lichao

2006-11-01

With interiorizing day by day management thought that regarding customer as the centre, forecasting customer demand becomes more and more important. In the demand forecast of customer relationship management, the traditional forecast methods have very great limitation because much uncertainty of the demand, these all require new modeling to meet the demands of development. In this paper, the notion is that forecasting the demand according to characteristics of the potential customer, then modeling by it. The model first depicts customer adopting uniform multiple indexes. Secondly, the model acquires characteristic customers on the basis of data warehouse and the technology of data mining. The last, there get the most similar characteristic customer by their comparing and forecast the demands of new customer by the most similar characteristic customer.

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

Science.gov (United States)

Llorach-Pares, Laura; Nonell-Canals, Alfons; Sanchez-Martinez, Melchor; Avila, Conxita

2017-11-27

Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A-G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium , against various protein kinases involved in Alzheimer's disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs.

Changing Professional Demands in Sustainable Regional Development: A Curriculum Design Process to meet Transboundary Competence

NARCIS (Netherlands)

Lansu, Angelique; Boon, Jo; Sloep, Peter; van Dam-Mieras, Rietje

2012-01-01

Lansu, A., Boon, J., Sloep, P. B., & Van Dam-Mieras, R. (Accepted). Changing Professional Demands in Sustainable Regional Development: A Curriculum Design Process to meet Transboundary Competence. Journal of Cleaner Production. [Special Issue: Learning for Sustainable Development in Regional

BATMAN: MOS Spectroscopy on Demand

Science.gov (United States)

Molinari, E.; Zamkotsian, F.; Moschetti, M.; Spano, P.; Boschin, W.; Cosentino, R.; Ghedina, A.; González, M.; Pérez, H.; Lanzoni, P.; Ramarijaona, H.; Riva, M.; Zerbi, F.; Nicastro, L.; Valenziano, L.; Di Marcantonio, P.; Coretti, I.; Cirami, R.

2016-10-01

Multi-Object Spectrographs (MOS) are the major instruments for studying primary galaxies and remote and faint objects. Current object selection systems are limited and/or difficult to implement in next generation MOS for space and ground-based telescopes. A promising solution is the use of MOEMS devices such as micromirror arrays, which allow the remote control of the multi-slit configuration in real time. TNG is hosting a novelty project for real-time, on-demand MOS masks based on MOEMS programmable slits. We are developing a 2048×1080 Digital-Micromirror-Device-based (DMD) MOS instrument to be mounted on the Galileo telescope, called BATMAN. It is a two-arm instrument designed for providing in parallel imaging and spectroscopic capabilities. With a field of view of 6.8×3.6 arcmin and a plate scale of 0.2 arcsec per micromirror, this astronomical setup can be used to investigate the formation and evolution of galaxies. The wavelength range is in the visible and the spectral resolution is R=560 for a 1 arcsec object, and the two arms will have 2k × 4k CCD detectors. ROBIN, a BATMAN demonstrator, has been designed, realized and integrated. We plan to have BATMAN first light by mid-2016.

Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat

Science.gov (United States)

Bentzley, Brandon S.; Jhou, Thomas C.; Aston-Jones, Gary

2014-01-01

Development of new treatments for drug addiction will depend on high-throughput screening in animal models. However, an addiction biomarker fit for rapid testing, and useful in both humans and animals, is not currently available. Economic models are promising candidates. They offer a structured quantitative approach to modeling behavior that is mathematically identical across species, and accruing evidence indicates economic-based descriptors of human behavior may be particularly useful biomarkers of addiction severity. However, economic demand has not yet been established as a biomarker of addiction-like behavior in animals, an essential final step in linking animal and human studies of addiction through economic models. We recently developed a mathematical approach for rapidly modeling economic demand in rats trained to self-administer cocaine. We show here that economic demand, as both a spontaneous trait and induced state, predicts addiction-like behavior, including relapse propensity, drug seeking in abstinence, and compulsive (punished) drug taking. These findings confirm economic demand as a biomarker of addiction-like behavior in rats. They also support the view that excessive motivation plays an important role in addiction while extending the idea that drug dependence represents a shift from initially recreational to compulsive drug use. Finally, we found that economic demand for cocaine predicted the efficacy of a promising pharmacotherapy (oxytocin) in attenuating cocaine-seeking behaviors across individuals, demonstrating that economic measures may be used to rapidly identify the clinical utility of prospective addiction treatments. PMID:25071176

Flexible Design and Operation of Multi-Stage Flash (MSF Desalination Process Subject to Variable Fouling and Variable Freshwater Demand

Directory of Open Access Journals (Sweden)

Said Alforjani Said

2013-10-01

Full Text Available This work describes how the design and operation parameters of the Multi-Stage Flash (MSF desalination process are optimised when the process is subject to variation in seawater temperature, fouling and freshwater demand throughout the day. A simple polynomial based dynamic seawater temperature and variable freshwater demand correlations are developed based on actual data which are incorporated in the MSF mathematical model using gPROMS models builder 3.0.3. In addition, a fouling model based on stage temperature is considered. The fouling and the effect of noncondensable gases are incorporated into the calculation of overall heat transfer co-efficient for condensers. Finally, an optimisation problem is developed where the total daily operating cost of the MSF process is minimised by optimising the design (no of stages and the operating (seawater rejected flowrate and brine recycle flowrate parameters.

Changing an automated drug inventory control system to a data base design.

Science.gov (United States)

Bradish, R A

1982-09-01

A pharmacy department's change from indexed sequential access files to a data base management system (DBMS) for purposes of automated inventory control is described. The DBMS has three main functional areas: (1) inventory ordering and accountability, (2) charging of interdepartmental and intradepartmental orders, and (3) data manipulation with report design for management control. There are seven files directly related to the inventory ordering and accountability area. Each record can be accessed directly or through another file. Information on the quantity of a drug on hand, drug(s) supplied by a specific vendor, status of a purchase order, or calculation of an estimated order quantity can be retrieved quickly. In the drug master file, two records contain a reorder point and safety-stock level that are determined by searching the entries in the order history file and vendor master file. The intradepartmental and interdepartmental orders section contains five files assigned to record and store information on drug distribution. All items removed from the stockroom and distributed are recorded, and reports can be generated for itemized bills, total cost by area, and as formatted files for the accounts payable department. The design, development, and implementation of the DBMS took approximately a year using a part-time pharmacist and minimal outside help, while the previous system required constant expensive help of a programmer/analyst. The DBMS has given the pharmacy department a flexible inventory management system with increased drug control, decreased operating expenses, increased use of department personnel, and the ability to develop and enhance other systems.

Design and mechanistic study of a novel gold nanocluster-based drug delivery system.

Science.gov (United States)

Li, Qinzhen; Pan, Yiting; Chen, Tiankai; Du, Yuanxin; Ge, Honghua; Zhang, Buchang; Xie, Jianping; Yu, Haizhu; Zhu, Manzhou

2018-05-22

Chemically-triggered drug delivery systems (DDSs) have been extensively studied as they do not require specialized equipment to deliver the drug and can deeply penetrate human tissue. However, their syntheses are complicated and they tend to be cytotoxic, which restricts their clinical utility. In this work, the self-regulated drug loading and release capabilities of peptide-protected gold nanoclusters (Pep-Au NCs) are investigated using vancomycin (Van) as the model drug. Gold nanoclusters (Au NCs) coated with a custom-designed pentapeptide are synthesized as drug delivery nanocarriers and loaded with Van - a spontaneous process reliant on the specific binding between Van and the custom-designed peptide. The Van-loaded Au NCs show comparable antimicrobial activity with Van on its own, and the number of Van released by the Pep-Au NCs is found to be proportional to the amount of bacteria present. The controlled nature of the Van release is very encouraging, and predominantly due to the stronger binding affinity of Van with bacteria than that with Au NCs. In addition, these fluorescent Au NCs could also be used to construct temperature sensors, which enable the in vitro and in vivo bioimaging.

Identification of designer drug 2C-E (4-ethyl-2, 5-dimethoxy-phenethylamine) in urine following a drug overdose.

Science.gov (United States)

Van Vrancken, Michael J; Benavides, Raul; Wians, Frank H

2013-01-01

In recent years, access to information regarding acquisition and synthesis of newer designer drugs has been at an all-time high due largely to the Internet. As these drugs have become more prevalent, laboratory techniques have been developed and refined to identify and screen for this burgeoning population of drugs. This provides a unique opportunity for learning about many of these methods. Laboratory testing techniques and instrumentation are obscure to many health care professionals, yet their results are crucial. Here, we present a case of an overdose of an uncommon designer drug (2C-E) and discuss the basics of liquid chromatography and mass spectrometry, two important techniques used in isolating and identifying the drug. Although often overlooked and taken for granted, these techniques can play a pivotal role in the diagnosis and subsequent management of select patients.

Metal complexes in cancer therapy – an update from drug design perspective

Directory of Open Access Journals (Sweden)

Ndagi U

2017-03-01

Full Text Available Umar Ndagi, Ndumiso Mhlongo, Mahmoud E Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, South Africa Abstract: In the past, metal-based compounds were widely used in the treatment of disease conditions, but the lack of clear distinction between the therapeutic and toxic doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg in 1960, a milestone in the history of metal-based compounds used in the treatment of cancers was witnessed. This forms the foundation for the modern era of the metal-based anticancer drugs. Platinum drugs, such as cisplatin, carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the treatment of cancer, but the delay in the therapeutic accomplishment of other metal-based compounds hampered the progress of research in this field. Recently, however, there has been an upsurge of activities relying on the structural information, aimed at improving and developing other forms of metal-based compounds and nonclassical platinum complexes whose mechanism of action is distinct from known drugs such as cisplatin. In line with this, many more metal-based compounds have been synthesized by redesigning the existing chemical structure through ligand substitution or building the entire new compound with enhanced safety and cytotoxic profile. However, because of increased emphasis on the clinical relevance of metal-based complexes, a few of these drugs are currently on clinical trial and many more are awaiting ethical approval to join the trial. In this review, we seek to give an overview of previous reviews on the cytotoxic effect of metal-based complexes while focusing more on newly designed metal-based complexes and their cytotoxic effect on the cancer cell lines, as well as on new approach to metal-based drug design and molecular target in cancer therapy. We are optimistic that the concept of selective

Web-based services for drug design and discovery.

Science.gov (United States)

Frey, Jeremy G; Bird, Colin L

2011-09-01

Reviews of the development of drug discovery through the 20(th) century recognised the importance of chemistry and increasingly bioinformatics, but had relatively little to say about the importance of computing and networked computing in particular. However, the design and discovery of new drugs is arguably the most significant single application of bioinformatics and cheminformatics to have benefitted from the increases in the range and power of the computational techniques since the emergence of the World Wide Web, commonly now referred to as simply 'the Web'. Web services have enabled researchers to access shared resources and to deploy standardized calculations in their search for new drugs. This article first considers the fundamental principles of Web services and workflows, and then explores the facilities and resources that have evolved to meet the specific needs of chem- and bio-informatics. This strategy leads to a more detailed examination of the basic components that characterise molecules and the essential predictive techniques, followed by a discussion of the emerging networked services that transcend the basic provisions, and the growing trend towards embracing modern techniques, in particular the Semantic Web. In the opinion of the authors, the issues that require community action are: increasing the amount of chemical data available for open access; validating the data as provided; and developing more efficient links between the worlds of cheminformatics and bioinformatics. The goal is to create ever better drug design services.

Heat effects on drug delivery across human skin

Science.gov (United States)

Hao, Jinsong; Ghosh, Priyanka; Li, S. Kevin; Newman, Bryan; Kasting, Gerald B.; Raney, Sam G.

2016-01-01

Introduction Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in vitro and in vivo methods to study them are of significant value to the development and evaluation of drug products dosed to the skin. Areas covered This review provides an overview of the underlying mechanisms and the observed effects of heat on the skin and on transdermal/topical drug delivery, thermoregulation and heat tolerability. The designs of several in vitro and in vivo heat effect studies and their results are reviewed. Expert opinion There is substantial evidence that elevated temperature can increase transdermal/topical drug delivery. However, in vitro and in vivo methods reported in the literature to study heat effects of transdermal/topical drug products have utilized inconsistent study conditions, and in vitro models require better characterization. Appropriate study designs and controls remain to be identified, and further research is warranted to evaluate in vitro-in vivo correlations and the ability of in vitro models to predict in vivo effects. The physicochemical and pharmacological properties of the drug(s) and the drug product, as well as dermal clearance and heat gradients may require careful consideration. PMID:26808472

Homology modeling and docking analyses of M. leprae Mur ligases reveals the common binding residues for structure based drug designing to eradicate leprosy.

Science.gov (United States)

Shanmugam, Anusuya; Natarajan, Jeyakumar

2012-06-01

Multi drug resistance capacity for Mycobacterium leprae (MDR-Mle) demands the profound need for developing new anti-leprosy drugs. Since most of the drugs target a single enzyme, mutation in the active site renders the antibiotic ineffective. However, structural and mechanistic information on essential bacterial enzymes in a pathway could lead to the development of antibiotics that targets multiple enzymes. Peptidoglycan is an important component of the cell wall of M. leprae. The biosynthesis of bacterial peptidoglycan represents important targets for the development of new antibacterial drugs. Biosynthesis of peptidoglycan is a multi-step process that involves four key Mur ligase enzymes: MurC (EC:6.3.2.8), MurD (EC:6.3.2.9), MurE (EC:6.3.2.13) and MurF (EC:6.3.2.10). Hence in our work, we modeled the three-dimensional structure of the above Mur ligases using homology modeling method and analyzed its common binding features. The residues playing an important role in the catalytic activity of each of the Mur enzymes were predicted by docking these Mur ligases with their substrates and ATP. The conserved sequence motifs significant for ATP binding were predicted as the probable residues for structure based drug designing. Overall, the study was successful in listing significant and common binding residues of Mur enzymes in peptidoglycan pathway for multi targeted therapy.

The role of illicit, licit, and designer drugs in the traffic in Hungary.

Science.gov (United States)

Institóris, László; Hidvégi, Előd; Dobos, Adrienn; Sija, Éva; Kereszty, Éva M; Tajti, László Balázs; Somogyi, Gábor Pál; Varga, Tibor

2017-06-01

The aim of this study was to investigate the prevalence and pattern of psychoactive substances among suspected DUID (Driving Under the Influence of Drugs) drivers in Hungary in 2014 and 2015. Blood and/or urine samples of 1252 suspected drivers (600 in 2014 and 652 in 2015) were analyzed for classical illicit and licit drugs, stimulant designer drugs (SDDs), and for synthetic cannabinoids, with 78.3% and 79.6% positive cases for at least one substance in 2014, and 2015, respectively. Impairment was proven in 39.2% (2014) and 35.7% (2015) of all drivers tested, based on the legal criteria of Hungary. Classical illicit drugs were found to be present in blood or urine of 89-61%, drivers tested. Drivers also tested positive for legal medications in 20-22%, SDDs in 21-28%, and synthetic cannabinoids in 15-19% of all cases. This indicates a drop in prevalence for classical illicit drugs and a slight but statistically non-significant increase for the other three substance groups. The distribution of drug types in each category were: [1] classical illicit drugs: cannabis (432), amphetamine (321), and cocaine (79); [2] medicines: alprazolam (94) and clonazepam (36); [3] SDDs: pentedrone (137) and α-PVP (33); [4] synthetic cannabinoids: AB-CHMINACA (46) and MDMB-CHMICA (30). The average age of illicit drug and SDD users was 30 years, while legal medications users were 36 years old on average, and the mean age of synthetic cannabinoid users was 26.5 years. The presence of both alcohol and at least one drug in samples was found in about 10% of the cases, both years. The ratio of multi-drug use was 33.0% in 2014 and 41.3% in 2015. Compared to former years the number of drivers who tested positive for drugs doubled in Hungary, but it is still low compared to alcohol positive cases. The relatively low detected rate of DUID can be explained by (1) combined alcohol consumption masking drug symptoms, (2) the absence of road-side tests for illicit and designer drugs and, (3) police

Molecular Thermodynamic Modeling and Design of Microencapsulation Systems for Drug Delivery

DEFF Research Database (Denmark)

Abildskov, Jens; O’Connell, John P.

2011-01-01

is based on fundamental thermodynamic relations and group contributions to properties of pure species (solvent, active ingredient and polymer) and their mixtures. The method is intended for pharmaceuticals with complex molecular structures, for which limited experimental information is known. Case studies......A systematic design strategy is given for computer-aided design of microparticle drug-delivery systems produced by solvent evaporation. In particular, design of solvents, polymer material, and external phase composition are considered for the case when the active ingredient is known. The procedure...... of solvent design are given....

Adjusting inkjet printhead parameters to deposit drugs into micro-sized reservoirs

Directory of Open Access Journals (Sweden)

Mau Robert

2016-09-01

Full Text Available Drug delivery systems (DDS ensure that therapeutically effective drug concentrations are delivered locally to the target site. For that reason, it is common to coat implants with a degradable polymer which contains drugs. However, the use of polymers as a drug carrier has been associated with adverse side effects. For that reason, several technologies have been developed to design polymer-free DDS. In literature it has been shown that micro-sized reservoirs can be applied as drug reservoirs. Inkjet techniques are capable of depositing drugs into these reservoirs. In this study, two different geometries of micro-sized reservoirs have been laden with a drug (ASA using a drop-on-demand inkjet printhead. Correlations between the characteristics of the drug solution, the operating parameters of the printhead and the geometric parameters of the reservoir are shown. It is indicated that wettability of the surface play a key role for drug deposition into micro-sized reservoirs.

Large Field Visualization with Demand-Driven Calculation

Science.gov (United States)

Moran, Patrick J.; Henze, Chris

1999-01-01

We present a system designed for the interactive definition and visualization of fields derived from large data sets: the Demand-Driven Visualizer (DDV). The system allows the user to write arbitrary expressions to define new fields, and then apply a variety of visualization techniques to the result. Expressions can include differential operators and numerous other built-in functions, ail of which are evaluated at specific field locations completely on demand. The payoff of following a demand-driven design philosophy throughout becomes particularly evident when working with large time-series data, where the costs of eager evaluation alternatives can be prohibitive.

Design of diversity and focused combinatorial libraries in drug discovery.

Science.gov (United States)

Young, S Stanley; Ge, Nanxiang

2004-05-01

Using well-characterized chemical reactions and readily available monomers, chemists are able to create sets of compounds, termed libraries, which are useful in drug discovery processes. The design of combinatorial chemical libraries can be complex and there has been much information recently published offering suggestions on how the design process can be carried out. This review focuses on literature with the goal of organizing current thinking. At this point in time, it is clear that benchmarking of current suggested methods is required as opposed to further new methods.

Design and fabrication of a PET/PTFE-based piezoelectric squeeze mode drop-on-demand inkjet printhead with interchangeable nozzle

KAUST Repository

Li, Erqiang

2010-09-01

A PET/PTFE-based piezoelectric squeeze mode drop-on-demand inkjet printhead with interchangeable nozzles is designed and fabricated. The printhead chamber is comprised of PET (polyethylene terephthalate) tubing or PTFE (polytetrafluoroethylene, or Teflon) tubing, which of a much softer material, than the conventionally used glass tubing. Applying the same electrical voltage, PET/PTFE-based printhead will generate a larger volume change in the material to be dispensed. The novel printhead fabricated herein has successfully dispensed liquids with viscosities up to 100 cps, as compared to 20 cps for the commercial printheads. Furthermore, PTFE-based printhead provides excellent anti-corrosive property when strongly corrosive inks are involved. The interchangeable nozzle design enables the same printhead to be fitted with nozzles of different orifice size, thus a clogged nozzle can be easily removed for cleaning or replacement. The characteristics of this novel printhead are also studied by dispensing glycerin-water solutions. © 2010 Elsevier B.V. All rights reserved.

Drug repurposing based on drug-drug interaction.

Science.gov (United States)

Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

2015-02-01

Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

An Optimization Model for Expired Drug Recycling Logistics Networks and Government Subsidy Policy Design Based on Tri-level Programming

OpenAIRE

Huang, Hui; Li, Yuyu; Huang, Bo; Pi, Xing

2015-01-01

In order to recycle and dispose of all people’s expired drugs, the government should design a subsidy policy to stimulate users to return their expired drugs, and drug-stores should take the responsibility of recycling expired drugs, in other words, to be recycling stations. For this purpose it is necessary for the government to select the right recycling stations and treatment stations to optimize the expired drug recycling logistics network and minimize the total costs of recycling and disp...

Market architecture and power demand management

International Nuclear Information System (INIS)

Rious, Vincent; Roques, Fabien

2014-12-01

Demand response is a cornerstone problem in electricity markets considering climate change constraint. Most liberalized electricity markets have a poor track record at developing demand response. In Europe, different models are considered for demand response, from a development under a regulated regime to a development under competitive perspectives. In this paper, focusing on demand response for mid-size and small consumers, we investigate which types of market signals should be sent to demand response aggregators to see demand response emerge as a competitive activity. Using data from the French power system over eight years, we compare the possible market design options to allow demand response to develop. Our simulations demonstrate that with the current market rules, demand response is not a profitable activity in the French electricity industry. Introducing a capacity remuneration could bring additional revenues to demand response aggregators if the power system has no over-capacity

The impact of South Korea's new drug-pricing policy on market competition among off-patent drugs.

Science.gov (United States)

Kwon, Hye-Young; Kim, Hyungmin; Godman, Brian; Reich, Michael R

2015-01-01

A new pricing policy was introduced in Korea in April 2012 with the aim of strengthening competition among off-patent drugs by eliminating price gaps between originators and generics. Examine the effect of newly implemented pricing policy. Retrospectively examining the effects through extracting from the National Health Insurance claims data a 30-month panel dataset (January 2011-June 2013) containing consumption data in four major therapeutic classes (antihypertensives, lipid-lowering drugs, antiulcerants and antidepressants). Proxies for market competition were examined before and after the policy. The new pricing policy did not enhance competition among off-patent drugs. In fact, price dispersion significantly decreased as opposed to the expected change. Originator-to-generic utilization increased 6.12 times (p = 0.000) after the new policy. The new pricing policy made no impact on competition among off-patent drugs. Competition in the off-patent market cannot be enhanced unless both supply and demand side measures are coordinated.

Demand Response Programs Design and Use Considering Intensive Penetration of Distributed Generation

OpenAIRE

Faria, Pedro; Vale, Zita; Baptista, José

2015-01-01

Further improvements in demand response programs implementation are needed in order to take full advantage of this resource, namely for the participation in energy and reserve market products, requiring adequate aggregation and remuneration of small size resources. The present paper focuses on SPIDER, a demand response simulation that has been improved in order to simulate demand response, including realistic power system simulation. For illustration of the simulator’s capabilities, the prese...

A train dispatching model based on fuzzy passenger demand forecasting during holidays

Directory of Open Access Journals (Sweden)

Fei Dou Dou

2013-03-01

Full Text Available Abstract: Purpose: The train dispatching is a crucial issue in the train operation adjustment when passenger flow outbursts. During holidays, the train dispatching is to meet passenger demand to the greatest extent, and ensure safety, speediness and punctuality of the train operation. In this paper, a fuzzy passenger demand forecasting model is put up, then a train dispatching optimization model is established based on passenger demand so as to evacuate stranded passengers effectively during holidays. Design/methodology/approach: First, the complex features and regularity of passenger flow during holidays are analyzed, and then a fuzzy passenger demand forecasting model is put forward based on the fuzzy set theory and time series theory. Next, the bi-objective of the train dispatching optimization model is to minimize the total operation cost of the train dispatching and unserved passenger volume during holidays. Finally, the validity of this model is illustrated with a case concerned with the Beijing-Shanghai high-speed railway in China. Findings: The case study shows that the fuzzy passenger demand forecasting model can predict outcomes more precisely than ARIMA model. Thus train dispatching optimization plan proves that a small number of trains are able to serve unserved passengers reasonably and effectively. Originality/value: On the basis of the passenger demand predictive values, the train dispatching optimization model is established, which enables train dispatching to meet passenger demand in condition that passenger flow outbursts, so as to maximize passenger demand by offering the optimal operation plan.

Towards appropriate design solutions for drug-resistant TB facilities in SA

CSIR Research Space (South Africa)

Parsons, SA

2010-07-01

Full Text Available South Africa has a high and increasing burden of both drugs-susceptible and drug-resistant tuberculosis. This disease has been declared an emergency in Africa. South Africa has committed itself to addressing this national crises by designing...

Effects of Daily Morphine Administration and Deprivation on Choice and Demand for Remifentanil and Cocaine in Rhesus Monkeys

Science.gov (United States)

Wade-Galuska, Tammy; Galuska, Chad M.; Winger, Gail

2011-01-01

Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been applied to this question. The present study assessed whether mild morphine withdrawal would increase demand for or choice of remifentanil or…

Distribution network design under demand uncertainty using genetic algorithm and Monte Carlo simulation approach: a case study in pharmaceutical industry

Science.gov (United States)

Izadi, Arman; Kimiagari, Ali Mohammad

2014-05-01

Distribution network design as a strategic decision has long-term effect on tactical and operational supply chain management. In this research, the location-allocation problem is studied under demand uncertainty. The purposes of this study were to specify the optimal number and location of distribution centers and to determine the allocation of customer demands to distribution centers. The main feature of this research is solving the model with unknown demand function which is suitable with the real-world problems. To consider the uncertainty, a set of possible scenarios for customer demands is created based on the Monte Carlo simulation. The coefficient of variation of costs is mentioned as a measure of risk and the most stable structure for firm's distribution network is defined based on the concept of robust optimization. The best structure is identified using genetic algorithms and 14 % reduction in total supply chain costs is the outcome. Moreover, it imposes the least cost variation created by fluctuation in customer demands (such as epidemic diseases outbreak in some areas of the country) to the logistical system. It is noteworthy that this research is done in one of the largest pharmaceutical distribution firms in Iran.

An Optimization Model for Expired Drug Recycling Logistics Networks and Government Subsidy Policy Design Based on Tri-level Programming.

Science.gov (United States)

Huang, Hui; Li, Yuyu; Huang, Bo; Pi, Xing

2015-07-09

In order to recycle and dispose of all people's expired drugs, the government should design a subsidy policy to stimulate users to return their expired drugs, and drug-stores should take the responsibility of recycling expired drugs, in other words, to be recycling stations. For this purpose it is necessary for the government to select the right recycling stations and treatment stations to optimize the expired drug recycling logistics network and minimize the total costs of recycling and disposal. This paper establishes a tri-level programming model to study how the government can optimize an expired drug recycling logistics network and the appropriate subsidy policies. Furthermore, a Hybrid Genetic Simulated Annealing Algorithm (HGSAA) is proposed to search for the optimal solution of the model. An experiment is discussed to illustrate the good quality of the recycling logistics network and government subsides obtained by the HGSAA. The HGSAA is proven to have the ability to converge on the global optimal solution, and to act as an effective algorithm for solving the optimization problem of expired drug recycling logistics network and government subsidies.

Drug design and discovery: translational biomedical science varies among countries.

Science.gov (United States)

Weaver, Ian N; Weaver, Donald F

2013-10-01

Drug design and discovery is an innovation process that translates the outcomes of fundamental biomedical research into therapeutics that are ultimately made available to people with medical disorders in many countries throughout the world. To identify which nations succeed, exceed, or fail at the drug design/discovery endeavor--more specifically, which countries, within the context of their national size and wealth, are "pulling their weight" when it comes to developing medications targeting the myriad of diseases that afflict humankind--we compiled and analyzed a comprehensive survey of all new drugs (small molecular entities and biologics) approved annually throughout the world over the 20-year period from 1991 to 2010. Based upon this analysis, we have devised prediction algorithms to ascertain which countries are successful (or not) in contributing to the worldwide need for effective new therapeutics. © 2013 Wiley Periodicals, Inc.

Design of stationary PEFC system configurations to meet heat and power demands

Science.gov (United States)

Wallmark, Cecilia; Alvfors, Per

This paper presents heat and power efficiencies of a modeled PEFC system and the methods used to create the system configuration. The paper also includes an example of a simulated fuel cell system supplying a building in Sweden with heat and power. The main method used to create an applicable fuel cell system configuration is pinch technology. This technology is used to evaluate and design a heat exchanger network for a PEFC system working under stationary conditions, in order to find a solution with high heat utilization. The heat exchanger network in the system connecting the reformer, the burner, gas cleaning, hot-water storage and the PEFC stack will affect the heat transferred to the hot-water storage and thereby the heating of the building. The fuel, natural gas, is reformed to a hydrogen-rich gas within a slightly pressurized system. The fuel processor investigated is steam reforming, followed by high- and low-temperature shift reactors and preferential oxidation. The system is connected to the electrical grid for backup and peak demands and to a hot-water storage to meet the varying heat demand for the building. The procedure for designing the fuel cell system installation as co-generation system is described, and the system is simulated for a specific building in Sweden during 1 year. The results show that the fuel cell system in combination with a burner and hot-water storage could supply the building with the required heat without exceeding any of the given limitations. The designed co-generation system will provide the building with most of its power requirements and would further generate income by sale of electricity to the power grid.

Data driven polypharmacological drug design for lung cancer: analyses for targeting ALK, MET, and EGFR

DEFF Research Database (Denmark)

Narayanan, Dilip; Gani, Osman ABSM; Gruber, Franz XE

2017-01-01

encoded into molecular mechanics force fields. Cheminformatics analyses of binding data show EGFR to be dissimilar to ALK and MET, but its structure shows how it may be co-targeted with the addition of a covalent trap. This suggests a strategy for the design of a focussed chemical library based on a pan......Drug design of protein kinase inhibitors is now greatly enabled by thousands of publicly available X-ray structures, extensive ligand binding data, and optimized scaffolds coming off patent. The extensive data begin to enable design against a spectrum of targets (polypharmacology); however...... consider polypharmacological targeting of protein kinases ALK, MET, and EGFR (and its drug resistant mutant T790M) in non small cell lung cancer as an example. Both EGFR and ALK represent sources of primary oncogenic lesions, while drug resistance arises from MET amplification and EGFR mutation. A drug...

[Costly drugs: analysis and proposals for the Mercosur countries].

Science.gov (United States)

Marín, Gustavo H; Polach, María Andrea

2011-08-01

Determine how the Mercosur countries access, regulate, and finance costly drugs and propose joint selection and financing strategies at the subregional level. Qualitative design, using content analyses of primary and secondary sources, document reviews, interviews, focus groups, and case studies. The variables selected included: selection criteria, access, financing, and regulations in the various countries. Costly drugs were divided into those that do not alter the natural course of the disease and those with demonstrated efficacy, using the defined daily dose to compare the costs of classical treatments and those involving costly drugs. The Mercosur countries generally lack formal strategies for dealing with the demand for costly drugs, and governments and insurers wind up financing them by court order. The case studies show that there are costly drugs whose efficacy has not been established but that nonetheless generate demand. The fragmentation of procurement, international commitments with regard to intellectual property, and low negotiating power exponentially increase the price of costly drugs, putting health system finances in jeopardy. Costly drugs must be regulated and rationally selected so that only those that substantively benefit people are accepted. To finance the drugs so selected, common country strategies are needed that include such options as flexible in trade agreements, the creation of national resource funds, or joint procurement by countries to enhance their negotiating power.

Reversible, on-demand generation of aqueous two-phase microdroplets

Science.gov (United States)

Collier, Charles Patrick; Retterer, Scott Thomas; Boreyko, Jonathan Barton; Mruetusatorn, Prachya

2017-08-15

The present invention provides methods of on-demand, reversible generation of aqueous two-phase microdroplets core-shell microbeads, microparticle preparations comprising the core-shell microbeads, and drug delivery formulation comprising the microparticle preparations. Because these aqueous microdroplets have volumes comparable to those of cells, they provide an approach to mimicking the dynamic microcompartmentation of biomaterial that naturally occurs within the cytoplasm of cells. Hence, the present methods generate femtoliter aqueous two-phase droplets within a microfluidic oil channel using gated pressure pulses to generate individual, stationary two-phase microdroplets with a well-defined time zero for carrying out controlled and sequential phase transformations over time. Reversible phase transitions between single-phase, two-phase, and core-shell microbead states are obtained via evaporation-induced dehydration and water rehydration.

New Product Development Based on Demand

OpenAIRE

Davis-Krook, Shelby

2015-01-01

The purpose of this thesis was to determine how to develop a new product based on demand within a target market for an international company. Specifically looking at developing a new product line in an already developed brand, Alpha Performance. The research I have conducted in the following topics may help Alpha Performance if they choose to use my findings to create a one of a kind woman’s clothing line based on the demands of the Finnish market: target market research, product demand rese...

Using computer-aided drug design and medicinal chemistry strategies in the fight against diabetes.

Science.gov (United States)

Semighini, Evandro P; Resende, Jonathan A; de Andrade, Peterson; Morais, Pedro A B; Carvalho, Ivone; Taft, Carlton A; Silva, Carlos H T P

2011-04-01

The aim of this work is to present a simple, practical and efficient protocol for drug design, in particular Diabetes, which includes selection of the illness, good choice of a target as well as a bioactive ligand and then usage of various computer aided drug design and medicinal chemistry tools to design novel potential drug candidates in different diseases. We have selected the validated target dipeptidyl peptidase IV (DPP-IV), whose inhibition contributes to reduce glucose levels in type 2 diabetes patients. The most active inhibitor with complex X-ray structure reported was initially extracted from the BindingDB database. By using molecular modification strategies widely used in medicinal chemistry, besides current state-of-the-art tools in drug design (including flexible docking, virtual screening, molecular interaction fields, molecular dynamics, ADME and toxicity predictions), we have proposed 4 novel potential DPP-IV inhibitors with drug properties for Diabetes control, which have been supported and validated by all the computational tools used herewith.

Rational Design of Novel Allosteric Dihydrofolate Reductase Inhibitors Showing Antibacterial Effects on Drug-Resistant Escherichia coli Escape Variants.

Science.gov (United States)

Srinivasan, Bharath; Rodrigues, João V; Tonddast-Navaei, Sam; Shakhnovich, Eugene; Skolnick, Jeffrey

2017-07-21

In drug discovery, systematic variations of substituents on a common scaffold and bioisosteric replacements are often used to generate diversity and obtain molecules with better biological effects. However, this could saturate the small-molecule diversity pool resulting in drug resistance. On the other hand, conventional drug discovery relies on targeting known pockets on protein surfaces leading to drug resistance by mutations of critical pocket residues. Here, we present a two-pronged strategy of designing novel drugs that target unique pockets on a protein's surface to overcome the above problems. Dihydrofolate reductase, DHFR, is a critical enzyme involved in thymidine and purine nucleotide biosynthesis. Several classes of compounds that are structural analogues of the substrate dihydrofolate have been explored for their antifolate activity. Here, we describe 10 novel small-molecule inhibitors of Escherichia coli DHFR, EcDHFR, belonging to the stilbenoid, deoxybenzoin, and chalcone family of compounds discovered by a combination of pocket-based virtual ligand screening and systematic scaffold hopping. These inhibitors show a unique uncompetitive or noncompetitive inhibition mechanism, distinct from those reported for all known inhibitors of DHFR, indicative of binding to a unique pocket distinct from either substrate or cofactor-binding pockets. Furthermore, we demonstrate that rescue mutants of EcDHFR, with reduced affinity to all known classes of DHFR inhibitors, are inhibited at the same concentration as the wild-type. These compounds also exhibit antibacterial activity against E. coli harboring the drug-resistant variant of DHFR. This discovery is the first report on a novel class of inhibitors targeting a unique pocket on EcDHFR.

Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases.

Science.gov (United States)

Sarafianos, Stefan G; Das, Kalyan; Hughes, Stephen H; Arnold, Eddy

2004-12-01

HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites.

Food safety information and food demand

DEFF Research Database (Denmark)

Smed, Sinne; Jensen, Jørgen Dejgård

2005-01-01

Purpose – The purpose of this paper is to analyze how news about food-related health risks affects consumers’ demands for safe food products. Design/methodology/approach – By identifying structural breaks in an econometrically estimated demand model, news with permanent impact on demand...... induces a permanent increase in the demand for pasteurized eggs, while more moderate negative news influences demand temporarily and to a lesser extent. There is, however, considerable variation in the response to food safety news across socio-demographic groups of consumers. Research limitations...... is distinguished from news with temporary impact. The Danish demand for pasteurized versus shell eggs is used as an illustrative case. Findings – Negative safety news about one product variety can provide significant stimulation to the demand for safe varieties. Severe negative news about the safety of shell eggs...

Intended and unintended consequences of China's zero markup drug policy.

Science.gov (United States)

Yi, Hongmei; Miller, Grant; Zhang, Linxiu; Li, Shaoping; Rozelle, Scott

2015-08-01

Since economic liberalization in the late 1970s, China's health care providers have grown heavily reliant on revenue from drugs, which they both prescribe and sell. To curb abuse and to promote the availability, safety, and appropriate use of essential drugs, China introduced its national essential drug list in 2009 and implemented a zero markup policy designed to decouple provider compensation from drug prescription and sales. We collected and analyzed representative data from China's township health centers and their catchment-area populations both before and after the reform. We found large reductions in drug revenue, as intended by policy makers. However, we also found a doubling of inpatient care that appeared to be driven by supply, instead of demand. Thus, the reform had an important unintended consequence: China's health care providers have sought new, potentially inappropriate, forms of revenue. Project HOPE—The People-to-People Health Foundation, Inc.

Thermo-responsive mesoporous silica/lipid bilayer hybrid nanoparticles for doxorubicin on-demand delivery and reduced premature release.

Science.gov (United States)

Zhang, Qing; Chen, Xuanxuan; Shi, Huihui; Dong, Gaoqiu; Zhou, Meiling; Wang, Tianji; Xin, Hongliang

2017-12-01

Hybrid nanocarriers based on mesoporous silica nanoparticles (MSNs) and supported lipid bilayer (SLB) have been studied as drug delivery system. It still remains challenges to develop these nanocarriers (SLB-MSNs) with on-demand drug release profile for chemotherapy. Here, we reported the biocompatible SLB-MSNs with high drug loading, which could release doxorubicin (DOX) in response to hyperthermia and reduce premature release. After synthesis of MSNs via a sol-gel procedure, the thermo-responsive SLB was deposited on the MSNs by sonication to completely seal the mesopores. The obtained SLB-MSNs consisted of 50 nm-sized MSN cores and 6.3 nm-thick SLB shells. Due to the big surface and pore volume of MSNs, the high drug loading content (7.30±0.02%) and encapsulation efficiency (91.16±0.28%) were achieved. The SLB blocking the mesopores reduced 50% of premature release and achieved on-demand release in a thermo-responsive manner. Moreover, SLB-MSNs showed good hemocompatibility at any tested concentration (25-700μg/mL), while bare MSNs caused 100% of hemolysis at concentration larger than 325μg/mL. In addition, in vitro U251 cell uptake experiment demonstrated that compared with uncapped MSNs, SLB-MSNs could prevent untargeted cellular uptake of DOX owing to reduced premature release and steric hindrance of PEG, which would be beneficial to minimize toxicity for healthy tissues. These results indicated that SLB-MSNs with thermo-responsive release capacity possessed great potential in future synergistic thermo-chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Cognitive task demands, self-control demands and the mental well-being of office workers.

Science.gov (United States)

Bridger, Robert S; Brasher, Kate

2011-09-01

The cognitive task demands of office workers and the self-control demands of their work roles were measured in a sample of 196 employees in two different office layouts using a self-report questionnaire, which was circulated electronically. Multiple linear regression analysis revealed that both factors were associated with mental well-being, but not with physical well-being, while controlling for exposure to psychosocial stressors. The interaction between cognitive task demands and self-control demands had the strongest association with mental well-being, suggesting that the deleterious effect of one was greater when the other was present. An exploratory analysis revealed that the association was stronger for employees working in a large open-plan office than for those working in smaller offices with more privacy. Frustration of work goals was the cognitive task demand having the strongest negative impact on mental well-being. Methodological limitations and scale psychometrics (particularly the use of the NASA Task Load Index) are discussed. STATEMENT OF RELEVANCE: Modern office work has high mental demands and low physical demands and there is a need to design offices to prevent adverse psychological reactions. It is shown that cognitive task demands interact with self-control demands to degrade mental well-being. The association was stronger in an open-plan office.

Do Convertible Bond Issuers Cater to Investor Demand?

NARCIS (Netherlands)

de Jong, Abe; Duca, Eric; Dutordoir, Marie

2013-01-01

We examine the impact of fluctuations in investor demand for convertible securities on convertible bond issue volumes, pricing, and design. We find evidence of a positive impact of investor demand proxies on convertible bond issue volumes. We also document significantly lower convertible bond

Maximum spectral demands in the near-fault region

Science.gov (United States)

Huang, Yin-Nan; Whittaker, Andrew S.; Luco, Nicolas

2008-01-01

The Next Generation Attenuation (NGA) relationships for shallow crustal earthquakes in the western United States predict a rotated geometric mean of horizontal spectral demand, termed GMRotI50, and not maximum spectral demand. Differences between strike-normal, strike-parallel, geometric-mean, and maximum spectral demands in the near-fault region are investigated using 147 pairs of records selected from the NGA strong motion database. The selected records are for earthquakes with moment magnitude greater than 6.5 and for closest site-to-fault distance less than 15 km. Ratios of maximum spectral demand to NGA-predicted GMRotI50 for each pair of ground motions are presented. The ratio shows a clear dependence on period and the Somerville directivity parameters. Maximum demands can substantially exceed NGA-predicted GMRotI50 demands in the near-fault region, which has significant implications for seismic design, seismic performance assessment, and the next-generation seismic design maps. Strike-normal spectral demands are a significantly unconservative surrogate for maximum spectral demands for closest distance greater than 3 to 5 km. Scale factors that transform NGA-predicted GMRotI50 to a maximum spectral demand in the near-fault region are proposed.

Excluding Orphan Drugs from the 340B Drug Discount Program: the Impact on 18 Critical Access Hospitals

Directory of Open Access Journals (Sweden)

Madeline Carpinelli Wallack

2012-01-01

Full Text Available Purpose: The 340B Drug Pricing Program is a federal program designed to reduce the amount that safety net providers spend on outpatient drugs. The Patient Protection and Affordable Health Care Act of 2010 extended eligibility for 340B to critical access hospitals (CAHs for all drugs except those designated as “orphan.” Because this policy is unprecedented, this study quantifies the gross financial impact that this exemption has on a group of CAHs. Methods: Drug spending for 2010 from 18 CAHs in Minnesota and Wisconsin are reviewed to identify the prevalence of orphan drug purchases and to calculate the price differentials between the 340B price and the hospitals’ current cost. Results: The 18 CAHs’ purchases of orphan drugs comprise an average of 44% of the total annual drug budgets, but only 5% of units purchased, thus representing a very high proportion of their expenditures. In the aggregate, the 18 hospitals would have saved $3.1 million ($171,000 average per hospital had purchases of drugs with orphan designations been made at the 340B price. Because CAH claims for Medicare are reimbursed on a cost-basis, the Federal government is losing an opportunity for savings. Conclusion: The high prevalence of orphan drug use and considerable potential for cost reduction through the 340B program demonstrate the loss of benefit to the hospitals, Federal government and the states.

The drug situation in Europe: an overview of data available on illicit drugs and new psychoactive substances from European monitoring in 2015.

Science.gov (United States)

Mounteney, Jane; Griffiths, Paul; Sedefov, Roumen; Noor, Andre; Vicente, Julián; Simon, Roland

2016-01-01

A central task for the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is to produce an annual report of the latest data available on drug demand and drug supply in Europe. This paper is intended to facilitate a better understanding of, and easier access to, the main quantitative European level data sets available in 2015. The European reporting system formally covers all 28 European Union (EU) Member States, Norway and Turkey and incorporates multiple indicators alongside an early warning system (EWS) on uncontrolled new psychoactive substances (NPS). While epidemiological information is based largely on registries, surveys and other routine data reported annually, the EWS collects case-based data on an ongoing basis. The 2015 reporting exercise is centred primarily on a set of standardized reporting tools. The most recent data provided by European countries are presented, including data on drug use, drug-related morbidity and mortality, treatment demand, drug markets and new psychoactive substances, with data tables provided and methodological information. A number of key results are highlighted for illustrative purposes. Drug prevalence estimates from national surveys since 2012 (last year prevalence of use among the 15-34 age band) range from 0.4% in Turkey to 22.1% in France for cannabis, from 0.2% in Greece and Romania to 4.2% in the United Kingdom for cocaine, from 0.1% in Italy and Turkey to 3% in the Czech Republic and the United Kingdom for ecstasy, and from 0.1% or less in Romania, Italy and Portugal to 2.5% in Estonia for amphetamine. Declining trends in new HIV detections among people who inject drugs are illustrated, in addition to presentation of a breakdown of NPS reported to the EU early warning system, which have risen exponentially from fewer than 20 a year between 2005 and 2008, to 101 reported in 2014. Structured information is now available on patterns and trends in drug consumption in Europe, which permits triangulation of

Design of massively parallel hardware multi-processors for highly-demanding embedded applications

NARCIS (Netherlands)

Jozwiak, L.; Jan, Y.

2013-01-01

Many new embedded applications require complex computations to be performed to tight schedules, while at the same time demanding low energy consumption and low cost. For implementation of these highly-demanding applications, highly-optimized application-specific multi-processor system-on-a-chip

Structure-based drug design for G protein-coupled receptors.

Science.gov (United States)

Congreve, Miles; Dias, João M; Marshall, Fiona H

2014-01-01

Our understanding of the structural biology of G protein-coupled receptors has undergone a transformation over the past 5 years. New protein-ligand complexes are described almost monthly in high profile journals. Appreciation of how small molecules and natural ligands bind to their receptors has the potential to impact enormously how medicinal chemists approach this major class of receptor targets. An outline of the key topics in this field and some recent examples of structure- and fragment-based drug design are described. A table is presented with example views of each G protein-coupled receptor for which there is a published X-ray structure, including interactions with small molecule antagonists, partial and full agonists. The possible implications of these new data for drug design are discussed. © 2014 Elsevier B.V. All rights reserved.

Aviation Frontiers: On-Demand Aircraft

Science.gov (United States)

Moore, Mark D.

2010-01-01

Throughout the 20th Century, NASA has defined the forefront of aeronautical technology, and the aviation industry owes much of its prosperity to this knowledge and technology. In recent decades, centralized aeronautics has become a mature discipline, which raises questions concerning the future aviation innovation frontiers. Three transformational aviation capabilities, bounded together by the development of a Free Flight airspace management system, have the potential to transform 21st Century society as profoundly as civil aviation transformed the 20th Century. These mobility breakthroughs will re-establish environmental sustainable centralized aviation, while opening up latent markets for civil distributed sensing and on-demand rural and regional transportation. Of these three transformations, on-demand aviation has the potential to have the largest market and productivity improvement to society. The information system revolution over the past 20 years shows that vehicles lead, and the interconnecting infrastructure to make them more effective follows; that is, unless on-demand aircraft are pioneered, a distributed Air Traffic Control system will likely never be established. There is no single technology long-pole that will enable on-demand vehicle solutions. However, fully digital aircraft that include electric propulsion has the potential to be a multi-disciplinary initiator of solid state technologies that can provide order of magnitude improvements in the ease of use, safety/reliability, community and environmental friendliness, and affordability.

Designing on-demand education for simultaneous development of domain-specific and self-directed learning skills

NARCIS (Netherlands)

Taminiau, E.M.C.; Kester, L.; Corbalan Perez, G.; Spector, J.M.; Kirschner, P.A.; Merriënboer, J.J.G. van

2015-01-01

On-demand education enables individual learners to choose their learning pathways according to their own learning needs. They must use self-directed learning (SDL) skills involving self-assessment and task selection to determine appropriate pathways for learning. Learners who lack these skills must

Designing on-demand education for simultaneous development of domain-specific and self-directed learning skills

NARCIS (Netherlands)

Taminiau, Bettine; Kester, Liesbeth; Corbalan, Gemma; Spector, J. Michael; Kirschner, Paul A.; Van Merriënboer, Jeroen

2016-01-01

On-demand education enables individual learners to choose their learning pathways according to their own learning needs. They must use self-directed learning (SDL) skills involving self-assessment and task selection to determine appropriate pathways for learning. Learners who lack these skills must

Intrinsic motivation and organizational identification among on-demand workers.

Science.gov (United States)

Rockmann, Kevin W; Ballinger, Gary A

2017-09-01

On-demand firms provide services for clients through a network of on-demand workers ready to complete specific tasks for a set contractual price. Given such on-demand work is defined by payment on short-term contracts with no obligation for continued employment, there is little reason to believe on-demand workers experience more than extrinsic motivation and a transactional relationship with the on-demand firm. However, using self-determination theory, we argue that to the degree that on-demand work fulfills innate psychological needs individual on-demand workers will develop intrinsic motivation, which further leads to organizational identification with the on-demand firm. Across 2 survey-based studies we find support for this path to organizational identification. This adds to the literature on motivation and identification by strengthening the link between individual needs and the individual-organizational relationship. Implications for theory and for the management of on-demand workers are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand.

Science.gov (United States)

Cox, Brittney M; Bentzley, Brandon S; Regen-Tuero, Helaina; See, Ronald E; Reichel, Carmela M; Aston-Jones, Gary

2017-06-01

Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth, and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in humans with addiction. The same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong. We tested the effects of systemic and microinfused oxytocin on demand for self-administered intravenous meth and reinstatement of extinguished meth seeking in male and female rats using a BE paradigm. Correlations between meth demand and meth seeking were assessed. Female rats showed greater demand (i.e., motivation) for meth compared with male rats. In both male and female rats, meth demand predicted reinstatement of meth seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, these effects of systemic oxytocin were mediated by actions in the nucleus accumbens. Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the nucleus accumbens. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

Science.gov (United States)

Guedes, Karen Marinho Maciel; Borges, Rosivaldo Santos; Fontes-Júnior, Enéas Andrade; Silva, Andressa Santa Brigida; Fernandes, Luanna Melo Pereira; Cartágenes, Sabrina Carvalho; Pinto, Ana Carla Godinho; Silva, Mallone Lopes; Queiroz, Luana Melo Diogo; Vieira, José Luís Fernandes; Sousa, Pergentino José Cunha; Maia, Cristiane Socorro Ferraz

2018-04-13

Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

An Optimization Model for Expired Drug Recycling Logistics Networks and Government Subsidy Policy Design Based on Tri-level Programming

Directory of Open Access Journals (Sweden)

Hui Huang

2015-07-01

Full Text Available In order to recycle and dispose of all people’s expired drugs, the government should design a subsidy policy to stimulate users to return their expired drugs, and drug-stores should take the responsibility of recycling expired drugs, in other words, to be recycling stations. For this purpose it is necessary for the government to select the right recycling stations and treatment stations to optimize the expired drug recycling logistics network and minimize the total costs of recycling and disposal. This paper establishes a tri-level programming model to study how the government can optimize an expired drug recycling logistics network and the appropriate subsidy policies. Furthermore, a Hybrid Genetic Simulated Annealing Algorithm (HGSAA is proposed to search for the optimal solution of the model. An experiment is discussed to illustrate the good quality of the recycling logistics network and government subsides obtained by the HGSAA. The HGSAA is proven to have the ability to converge on the global optimal solution, and to act as an effective algorithm for solving the optimization problem of expired drug recycling logistics network and government subsidies.

Mobility on Demand Operational Concept Report.

Science.gov (United States)

2017-09-10

This operational concept report provides an overview of the Mobility on Demand (MOD) concept and its evolution, description of the MOD ecosystem in a supply and demand framework, and its stakeholders and enablers. Leveraging the MOD ecosystem framewo...

The impact of predicted demand on energy production

Science.gov (United States)

El kafazi, I.; Bannari, R.; Aboutafail, My. O.

2018-05-01

Energy is crucial for human life, a secure and accessible supply of power is essential for the sustainability of societies. Economic development and demographic progression increase energy demand, prompting countries to conduct research and studies on energy demand and production. Although, increasing in energy demand in the future requires a correct determination of the amount of energy supplied. Our article studies the impact of demand on energy production to find the relationship between the two latter and managing properly the production between the different energy sources. Historical data of demand and energy production since 2000 are used. The data are processed by the regression model to study the impact of demand on production. The obtained results indicate that demand has a positive and significant impact on production (high impact). Production is also increasing but at a slower pace. In this work, Morocco is considered as a case study.

On Inventory Control For Perishable Inventory Systems Subject To Uncertainties On Customer Demands

OpenAIRE

Abbou , Rosa; Loiseau , Jean-Jacques; Khaldi , Hajer; Farraa , Berna ,

2017-01-01

International audience; This paper deals with the inventory controller design for constrained production systems subject to uncertainties on the customer demands. The case study focuses on the inventory regulation problem in production systems where contain perishable finite products. Such systems are characterized by the presence of delays due to production processes, and constraints from the instantaneous inventory level, production level and the finite capacities of stocks. To do that, we ...

DataBase on Demand

International Nuclear Information System (INIS)

Aparicio, R Gaspar; Gomez, D; Wojcik, D; Coz, I Coterillo

2012-01-01

At CERN a number of key database applications are running on user-managed MySQL database services. The database on demand project was born out of an idea to provide the CERN user community with an environment to develop and run database services outside of the actual centralised Oracle based database services. The Database on Demand (DBoD) empowers the user to perform certain actions that had been traditionally done by database administrators, DBA's, providing an enterprise platform for database applications. It also allows the CERN user community to run different database engines, e.g. presently open community version of MySQL and single instance Oracle database server. This article describes a technology approach to face this challenge, a service level agreement, the SLA that the project provides, and an evolution of possible scenarios.

Design of new polymeric formulations for drug nanocarriers

Science.gov (United States)

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

2012-07-01

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

Pill testing or drug checking in Australia: Acceptability of service design features.

Science.gov (United States)

Barratt, Monica J; Bruno, Raimondo; Ezard, Nadine; Ritter, Alison

2018-02-01

This study aimed to determine design features of a drug-checking service that would be feasible, attractive and likely to be used by Australian festival and nightlife attendees. Web survey of 851 Australians reporting use of psychostimulants and/or hallucinogens and attendance at licensed venues past midnight and/or festivals in the past year (70% male; median age 23 years). A drug-checking service located at festivals or clubs would be used by 94%; a fixed-site service external to such events by 85%. Most (80%) were willing to wait an hour for their result. Almost all (94%) would not use a service if there was a possibility of arrest, and a majority (64%) would not use a service that did not provide individual feedback of results. Drug-checking results were only slightly more attractive if they provided comprehensive quantitative results compared with qualitative results of key ingredients. Most (93%) were willing to pay up to $5, and 68% up to $10, per test. One-third (33%) reported willingness to donate a whole dose for testing: they were more likely to be male, younger, less experienced, use drugs more frequently and attend venues/festivals less frequently. In this sample, festival- or club-based drug-checking services with low wait times and low cost appear broadly attractive under conditions of legal amnesty and individualised feedback. Quantitative analysis of ecstasy pills requiring surrender of a whole pill may appeal to a minority in Australia where pills are more expensive than elsewhere. [Barratt MJ, Bruno R, Ezard N, Ritter A. Pill testing or drug checking in Australia: Acceptability of service design features. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Relationship between job demand and burnout in nurses: does it depend on work engagement?

Science.gov (United States)

García-Sierra, Rosa; Fernández-Castro, Jordi; Martínez-Zaragoza, Fermín

2016-09-01

The present study aimed to deepen the understanding of the relationships among job demands, control, social support, burnout and engagement in nurses. Burnout is a prevalent phenomenon among nurses because of the interaction between high demands and low resources, according to the job demands-resources model. A descriptive, correlational design was used in a stratified random sample of 100 nurses recruited from two Spanish hospitals. Job demand, social support, control, engagement, and burnout were measured. Data were analysed by hierarchical regression analysis. Social support is a significant predictor of nurses' engagement and demands is a predictor of nurses' burnout. Work engagement moderates the relationship between job demands and burnout. The process that leads to burnout and the process that leads to engagement are not isolated processes; engagement acts as a moderator of burnout. The prevailing paradigm in combating burnout in nursing can be changed and could be based on the enhancement of nurses' strengths through increasing engagement. © 2016 John Wiley & Sons Ltd.

Job demands-resources model

OpenAIRE

Bakker, Arnold; Demerouti, Eva

2013-01-01

markdownabstract* The question of what causes job stress and what motivates people has received a lot of research attention during the past five decades. In this paper, we discuss Job Demands-Resources (JD-R) theory, which represents an extension of the Job Demands-Resources model (Bakker & Demerouti, 2007; Demerouti, Bakker, Nachreiner, & Schaufeli, 2001) and is inspired by job design and job stress theories. JD-R theory explains how job demands and resources have unique and multiplicative e...

Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations.

Science.gov (United States)

Singh, Pankaj Kumar; Negi, Arvind; Gupta, Pawan Kumar; Chauhan, Monika; Kumar, Raj

2016-08-01

Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.

Capacity market design and renewable energy: Performance incentives, qualifying capacity, and demand curves

Energy Technology Data Exchange (ETDEWEB)

Botterud, Audun; Levin, Todd; Byers, Conleigh

2018-01-01

A review of capacity markets in the United States in the context of increasing levels of variable renewable energy finds substantial differences with respect to incentives for operational performance, methods to calculate qualifying capacity for variable renewable energy and energy storage, and demand curves for capacity. The review also reveals large differences in historical capacity market clearing prices. The authors conclude that electricity market design must continue to evolve to achieve cost-effective policies for resource adequacy.

Site Identification by Ligand Competitive Saturation (SILCS) Simulations for Fragment-Based Drug Design

OpenAIRE

Faller, Christina E.; Raman, E. Prabhu; MacKerell, Alexander D.; Guvench, Olgun

2015-01-01

Fragment-based drug design (FBDD) involves screening low molecular weight molecules (“fragments”) that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind non-overlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR ...

Designing an intuitive web application for drug discovery scientists.

Science.gov (United States)

Karamanis, Nikiforos; Pignatelli, Miguel; Carvalho-Silva, Denise; Rowland, Francis; Cham, Jennifer A; Dunham, Ian

2018-01-11

We discuss how we designed the Open Targets Platform (www.targetvalidation.org), an intuitive application for bench scientists working in early drug discovery. To meet the needs of our users, we applied lean user experience (UX) design methods: we started engaging with users very early and carried out research, design and evaluation activities within an iterative development process. We also emphasize the collaborative nature of applying lean UX design, which we believe is a foundation for success in this and many other scientific projects. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structured outpatient treatment of alcohol vs. drug dependencies.

Science.gov (United States)

Washton, A M

1990-01-01

This chapter describes the rationale, indications, design, and use of a structured outpatient treatment approach as an effective alternative to residential treatment for alcohol and drug dependencies. An increasing demand for outpatient treatment services is being created by a combination of clinical and economic factors, including the influx of employed drug abusers who do not need or desire residential care and mounting financial pressures to contain health care costs. To be effective as a primary treatment modality, outpatient programs must be highly structured and intensive and able to deal with the full spectrum of alcohol and drug addictions. Perpetuating the historical separation between alcoholism and drug abuse treatment programs is unnecessary and counterproductive, although certain modifications in treatment approaches are needed to accommodate the distinctive characteristics of particular classes of drugs and the people who use them. The "outpatient rehab," a treatment model that approximates the intensity of inpatient treatment on an outpatient basis, may help to maximize the clinical efficacy and cost-effectiveness of outpatient treatment as a viable alternative to residential care. Initial treatment results with this model are encouraging.

Insurance companies' perspectives on the orphan drug pipeline.

Science.gov (United States)

Handfield, Robert; Feldstein, Josh

2013-11-01

costs, and two thirds are relying on prior authorization as a means to control costs. More than 80% of the companies are not using cost-effectiveness methodologies with regard to rare diseases, generally because of a lack of the availability of medicines to facilitate such comparisons. CEA is used by less than 20% of our study sample of payers in dealing with orphan drug policies. Evaluating cost-effectiveness is a valuable strategy for payers seeking to facilitate appropriate access and coverage decision-making related to orphan drugs, but it is not well understood or adapted by private insurance companies. Health economists, along with providers and payers, must work together to design rational methodologies to evaluate the value of orphan drugs, perhaps by adopting cost-effectiveness methodologies to consider a compound's total research and development and commercialization demands relative to its cost-effectiveness.

National Household Survey on Drug Abuse (NHSDA-1999)

Data.gov (United States)

U.S. Department of Health & Human Services — The National Household Survey on Drug Abuse (NHSDA) series measures the prevalence and correlates of drug use in the United States. The surveys are designed to...

National Household Survey on Drug Abuse (NHSDA-1998)

Data.gov (United States)

U.S. Department of Health & Human Services — The National Household Survey on Drug Abuse (NHSDA) series measures the prevalence and correlates of drug use in the United States. The surveys are designed to...

National Household Survey on Drug Abuse (NHSDA-2001)

Data.gov (United States)

U.S. Department of Health & Human Services — The National Household Survey on Drug Abuse (NHSDA) series measures the prevalence and correlates of drug use in the United States. The surveys are designed to...

National Household Survey on Drug Abuse (NHSDA-2000)

Data.gov (United States)

U.S. Department of Health & Human Services — The National Household Survey on Drug Abuse (NHSDA) series measures the prevalence and correlates of drug use in the United States. The surveys are designed to...

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

DEFF Research Database (Denmark)

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...... computational tools, able to aid in drug-design in a fast and cheap fashion, compared to conventional pharmacological techniques....... mu-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 drug-design.......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...

Effect of fare and travel time on the demand for domestic air transportation

Science.gov (United States)

Eriksen, S. E.; Liu, E. W.

1979-01-01

An econometric travel demand model was presented. The model was used for analyzing long haul domestic passenger markets in the United States. The results showed the sensitivities of demand to changes in fares and speed reflecting technology through more efficient aircraft designs.

Survey of Models on Demand, Customer Base-Line and Demand Response and Their Relationships in the Power Market

OpenAIRE

Heshmati, Almas

2012-01-01

The increasing use of demand-side management as a tool to reliably meet electricity demand at peak time has stimulated interest among researchers, consumers and producer organizations, managers, regulators and policymakers, This research reviews the growing literature on models used to study demand, consumer baseline (CBL) and demand response in the electricity market. After characterizing the general demand models, it reviews consumer baseline based on which further study the demand response...

Auction-Based Cloud Service Pricing and Penalty with Availability on Demand

Directory of Open Access Journals (Sweden)

Xiaohong Wu

2018-04-01

Full Text Available Availability is one of the main concerns of cloud users, and cloud providers always try to provide higher availability to improve user satisfaction. However, higher availability results in higher provider costs and lower social welfare. In this paper, taking into account both the users’ valuation and desired availability, we design resource allocation, pricing and penalty mechanisms with availability on demand. Considering two scenarios: public availability in which the desired availabilities of all users are public information, and private availability in which the desired availabilities are private information of users, and, analyzing the possible behaviours of users, we design a truthful deterministic mechanism with 2-approximation in public availability scenario and a universal truthful mechanism with 1 1 + γ approximation in private availability scenario, where γ is the backup ratio of resources with the highest availability. The experiment results show that our mechanisms significantly improve the social welfare compared to the mechanism without considering availability demand of users.

Towards Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis.

Science.gov (United States)

Francipane, Maria Giovanna; Lagasse, Eric

2016-09-01

In recent years, functional three-dimensional (3D) tissue generation in vitro has been significantly advanced by tissue-engineering methods, achieving better reproduction of complex native organs compared to conventional culture systems. This review will discuss traditional 3D cell culture techniques as well as newly developed technology platforms. These recent techniques provide new possibilities in the creation of human body parts and provide more accurate predictions of tissue response to drug and chemical challenges. Given the rapid advancement in the human induced pluripotent stem cell (iPSC) field, these platforms also hold great promise in the development of patient-specific, transplantable tissues and organs on demand.

Ebola virus: A gap in drug design and discovery - experimental and computational perspective.

Science.gov (United States)

Balmith, Marissa; Faya, Mbuso; Soliman, Mahmoud E S

2017-03-01

The Ebola virus, formally known as the Ebola hemorrhagic fever, is an acute viral syndrome causing sporadic outbreaks that have ravaged West Africa. Due to its extreme virulence and highly transmissible nature, Ebola has been classified as a category A bioweapon organism. Only recently have vaccine or drug regimens for the Ebola virus been developed, including Zmapp and peptides. In addition, existing drugs which have been repurposed toward anti-Ebola virus activity have been re-examined and are seen to be promising candidates toward combating Ebola. Drug development involving computational tools has been widely employed toward target-based drug design. Screening large libraries have greatly stimulated research toward effective anti-Ebola virus drug regimens. Current emphasis has been placed on the investigation of host proteins and druggable viral targets. There is a huge gap in the literature regarding guidelines in the discovery of Ebola virus inhibitors, which may be due to the lack of information on the Ebola drug targets, binding sites, and mechanism of action of the virus. This review focuses on Ebola virus inhibitors, drugs which could be repurposed to combat the Ebola virus, computational methods which study drug-target interactions as well as providing further insight into the mode of action of the Ebola virus. © 2016 John Wiley & Sons A/S.

Wilderness Recreation Demand: A Comparison of Travel Cost and On-Site Cost Models

Science.gov (United States)

J.M. Bowker; A. Askew; L. Seymour; J.P. Zhu; D. English; C.M. Starbuck

2009-01-01

This study used travel cost and on-site day cost models, coupled with the Forest Service’s National Visitor Use Monitoring data, to examine the demand for and value of recreation access to designated Wilderness.

The impact of changing technology on the demand for air transportation

Science.gov (United States)

Kneafsey, J. T.; Taneja, N. K.

1978-01-01

Demand models for air transportation that are sensitive to the impact of changing technology were developed. The models are responsive to potential changes in technology, and to changing economic, social, and political factors as well. In addition to anticipating the wide differences in the factors influencing the demand for long haul and short haul air travel, the models were designed to clearly distinguish among the unique features of these markets.

Design of a RESTful web information system for drug prescription and administration.

Science.gov (United States)

Bianchi, Lorenzo; Paganelli, Federica; Pettenati, Maria Chiara; Turchi, Stefano; Ciofi, Lucia; Iadanza, Ernesto; Giuli, Dino

2014-05-01

Drug prescription and administration processes strongly impact on the occurrence of risks in medical settings for they can be sources of adverse drug events (ADEs). A properly engineered use of information and communication technologies has proven to be a promising approach to reduce these risks. In this study, we propose PHARMA, a web information system which supports healthcare staff in the secure cooperative execution of drug prescription, transcription and registration tasks. PHARMA allows the easy sharing and management of documents containing drug-related information (i.e., drug prescriptions, medical reports, screening), which is often inconsistent and scattered across different information systems and heterogeneous organization domains (e.g., departments, other hospital facilities). PHARMA enables users to access such information in a consistent and secure way, through the adoption of REST and web-oriented design paradigms and protocols. We describe the implementation of the PHARMA prototype, and we discuss the results of the usability evaluation that we carried out with the staff of a hospital in Florence, Italy.

Optimal Drug Policy in Low-Income Neighborhoods

Science.gov (United States)

Chang, Sheng-Wen; Coulson, N. Edward; Wang, Ping

2015-01-01

The control of drug activity currently favors supply-side policies: drug suppliers in the U.S. face a higher arrest rate and longer sentences than demanders. We construct a simple model of drug activity with search and entry frictions in labor and drug markets. Our calibration analysis suggests a strong “dealer replacement effect.” As a result, given a variety of community objectives, it is beneficial to lower supplier arrests and raise the demand arrest rate from current values. A 10% shift from supply-side to demand-side arrests can reduce the population of potential drug dealers by 22–25,000 and raise aggregate local income by $380–400 million, at 2002 prices. (JEL Classification: D60, J60, K42, H70) PMID:27616878

In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

Science.gov (United States)

Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

2018-02-01

For a drug, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

Directory of Open Access Journals (Sweden)

Hongbin Yang

2018-02-01

Full Text Available During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts.

Science.gov (United States)

Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

2018-01-01

During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

Drug-drug interactions among recently hospitalised patients--frequent but mostly clinically insignificant

DEFF Research Database (Denmark)

Glintborg, Bente; Andersen, Stig Ejdrup; Dalhoff, Kim

2005-01-01

OBJECTIVE: Patients use and store considerable amounts of drugs. The aim of the present study was to identify potential drug-drug interactions between drugs used by patients recently discharged from the hospital and, subsequently, to estimate the clinical implications of these interactions. METHODS......: Patients were visited within 1 week following their discharge from hospital and interviewed about their drug use. Stored products were inspected. We used a bibliography (Hansten and Horn; Wolters Kluwer Health, St. Louis, Mo., 2004) to identify and classify potential drug-drug interactions. RESULTS......: eight per patient; range: 1-24). With respect to those drugs used daily or on demand, 476 potential interactions were identified (126 patients); none were class 1 (always avoid drug combination) and 25 were class 2 (usually avoid combination; 24 patients). Eleven of the potential class 2 interactions...

On-Demand Cell Internal Short Circuit Device

Science.gov (United States)

Darcy, Eric; Keyser, Matthew

2014-01-01

A device implantable in Li-ion cells that can generate a hard internal short circuit on-demand by exposing the cell to 60?C has been demonstrated to be valuable for expanding our understanding of cell responses. The device provides a negligible impact to cell performance and enables the instigation of the 4 general categories of cell internal shorts to determine relative severity and cell design susceptibility. Tests with a 18650 cell design indicates that the anode active material short to the aluminum cathode current collector tends to be more catastrophic than the 3 other types of internal shorts. Advanced safety features (such as shutdown separators) to prevent or mitigate the severity of cell internal shorts can be verified with this device. The hard short success rate achieved to date in 18650 cells is about 80%, which is sufficient for using these cells in battery assemblies for field-failure-relevant, cell-cell thermal runaway propagation verification tests

Celiac Disease and Drug-Based Therapies: Inquiry into Patients Demands.

Science.gov (United States)

Branchi, Federica; Tomba, Carolina; Ferretti, Francesca; Norsa, Lorenzo; Roncoroni, Leda; Bardella, Maria Teresa; Conte, Dario; Elli, Luca

2016-01-01

Medical research is looking for alternative drug-based options to the gluten-free diet (GFD) for celiac disease. We aimed at evaluating the need for alternative therapies perceived by celiac patients. During the 2013 meeting of the Lombardy section of the Italian Celiac Patients Association, adult subjects were invited to fill in a questionnaire investigating their clinical profile in relation to compliance to the diet, quality of life (QOL) as well as their opinion on alternative therapies. Three hundred and seventy two patients (76 m, mean age 41.7 ± 13.9 years) completed the questionnaire. Patients reported a significant improvement in health status (HS) and QOL after the diet was started (p < 0.001). The GFD was accepted by 88% patients, but the need for alternative therapies was reported by 65%. Subjects expressing the need for a drug-based therapy showed a lower increase in QOL (p = 0.003) and HS (p = 0.005) on GFD. The preferred option for an alternative therapy was the use of enzymes (145 subjects), followed by a vaccine (111 subjects). The GFD is favorably accepted by most celiac patients. Nevertheless, a proportion of patients pronounce themselves in favor of the development of alternative drugs. © 2016 S. Karger AG, Basel.

Drug Partitioning in Micellar Media and Its Implications in Rational Drug Design: Insights with Streptomycin.

Science.gov (United States)

Judy, Eva; Pagariya, Darshna; Kishore, Nand

2018-03-20

Oral bioavailability of a drug molecule requires its effective delivery to the target site. In general, majority of synthetically developed molecular entities have high hydrophobic nature as well as low bioavailability, therefore the need for suitable delivery vehicles arises. Self-assembled structures such as micelles, niosomes, and liposomes have been used as effective delivery vehicles and studied extensively. However, the information available in literature is mostly qualitative in nature. We have quantitatively investigated the partitioning of antibiotic drug streptomycin into cationic, nonionic, and a mixture of cationic and nonionic surfactant micelles and its interaction with the transport protein serum albumin upon subsequent delivery. A combination of calorimetry and spectroscopy has been used to obtain the thermodynamic signatures associated with partitioning and interaction with the protein and the resulting conformational changes in the latter. The results have been correlated with other class of drugs of different nature to understand the role of molecular features in the partitioning process. These studies are oriented toward understanding the physical chemistry of partitioning of a variety of drug molecules into suitable delivery vehicles and hence establishing structure-property-energetics relationships. Such studies provide general guidelines toward a broader goal of rational drug design.

NMR screening in fragment-based drug design: a practical guide.

Science.gov (United States)

Kim, Hai-Young; Wyss, Daniel F

2015-01-01

Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

On-demand Antimicrobial Treatment with Antibiotic-Loaded Porous Silicon Capped with a pH-Responsive Dual Plasma Polymer Barrier.

Science.gov (United States)

Vasani, Roshan B; Szili, Endre J; Rajeev, Gayathri; Voelcker, Nicolas H

2017-07-04

Chronic wounds are a major socio-economic problem. Bacterial infections in such wounds are a major contributor to lack of wound healing. An early indicator of wound infection is an increase in pH of the wound fluid. Herein, we describe the development of a pH-responsive drug delivery device that can potentially be used for wound decontamination in situ and on-demand in response to an increase in the pH of the wound environment. The device is based on a porous silicon film that provides a reservoir for encapsulation of an antibiotic within the pores. Loaded porous silicon is capped with dual plasma polymer layers of poly(1,7-octadiene) and poly(acrylic acid), which provide a pH-responsive barrier for on-demand release of the antibiotic. We demonstrate that release of the antibiotic is inhibited in aqueous buffer at pH 5, whereas the drug is released in a sustainable manner at pH 8. Importantly, the released drug was bacteriostatic against the Pseudomonas aeruginosa wound pathogen. In the future, incorporation of the delivery device into wound dressings could potentially be utilized for non-invasive decontamination of wounds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of capacity incentive and energy compensation for demand response programs

Science.gov (United States)

Liu, Zhoubin; Cui, Wenqi; Shen, Ran; Hu, Yishuang; Wu, Hui; Ye, Chengjin

2018-02-01

Variability and Uncertainties caused by renewable energy sources have called for large amount of balancing services. Demand side resources (DSRs) can be a good alternative of traditional generating units to provide balancing service. In the areas where the electricity market has not been fully established, e.g., China, DSRs can help balance the power system with incentive-based demand response programs. However, there is a lack of information about the interruption cost of consumers in these areas, making it hard to determine the rational amount of capacity incentive and energy compensation for the participants of demand response programs. This paper proposes an algorithm to calculate the amount of capacity incentive and energy compensation for demand response programs when there lacks the information about interruption cost. Available statistical information of interruption cost in referenced areas is selected as the referenced data. Interruption cost of the targeted area is converted from the referenced area by product per electricity consumption. On this basis, capacity incentive and energy compensation are obtained to minimize the payment to consumers. Moreover, the loss of consumers is guaranteed to be covered by the revenue they earned from load serving entities.

An adaptive drug delivery design using neural networks for effective treatment of infectious diseases: a simulation study.

Science.gov (United States)

Padhi, Radhakant; Bhardhwaj, Jayender R

2009-06-01

An adaptive drug delivery design is presented in this paper using neural networks for effective treatment of infectious diseases. The generic mathematical model used describes the coupled evolution of concentration of pathogens, plasma cells, antibodies and a numerical value that indicates the relative characteristic of a damaged organ due to the disease under the influence of external drugs. From a system theoretic point of view, the external drugs can be interpreted as control inputs, which can be designed based on control theoretic concepts. In this study, assuming a set of nominal parameters in the mathematical model, first a nonlinear controller (drug administration) is designed based on the principle of dynamic inversion. This nominal drug administration plan was found to be effective in curing "nominal model patients" (patients whose immunological dynamics conform to the mathematical model used for the control design exactly. However, it was found to be ineffective in curing "realistic model patients" (patients whose immunological dynamics may have off-nominal parameter values and possibly unwanted inputs) in general. Hence, to make the drug delivery dosage design more effective for realistic model patients, a model-following adaptive control design is carried out next by taking the help of neural networks, that are trained online. Simulation studies indicate that the adaptive controller proposed in this paper holds promise in killing the invading pathogens and healing the damaged organ even in the presence of parameter uncertainties and continued pathogen attack. Note that the computational requirements for computing the control are very minimal and all associated computations (including the training of neural networks) can be carried out online. However it assumes that the required diagnosis process can be carried out at a sufficient faster rate so that all the states are available for control computation.

Mixing monoclonal antibody formulations using bottom-mounted mixers: impact of mechanism and design on drug product quality.

Science.gov (United States)

Gikanga, Benson; Chen, Yufei; Stauch, Oliver B; Maa, Yuh-Fun

2015-01-01

Using bottom-mounted mixers, particularly those that are magnetically driven, is becoming increasingly common during the mixing process in pharmaceutical and biotechnology manufacturing because of their associated low risk of contamination, ease of use, and ability to accommodate low minimum mixing volumes. Despite these benefits, the impact of bottom-mounted mixers on biologic drug product is not yet fully understood and is scarcely reported. This study evaluated four bottom-mounted mixers to assess their impact on monoclonal antibody formulations. Changes in product quality (size variants, particles, and turbidity) and impact on process performance (sterile filtration) were evaluated after mixing. The results suggested that mixers that are designed to function with no contact between the impeller and the drive unit are the most favorable and gentle to monoclonal antibody molecules. Designs with contact or a narrow clearance tended to shear and grind the protein and resulted in high particle count in the liquid, which would subsequently foul a filter membrane during sterile filtration using a 0.22 μm pore size filter. Despite particle formation, increases in turbidity of the protein solution and protein aggregation/fragmentation were not detected. Further particle analysis indicated particles in the range of 0.2-2 μm are responsible for filter fouling. A small-scale screening model was developed using two types of magnetic stir bars mimicking the presence or absence of contact between the impeller and drive unit in the bottom-mounted mixers. The model is capable of differentiating the sensitivity of monoclonal antibody formulations to bottom-mounted mixers with a small sample size. This study fills an important gap in understanding a critical bioprocess unit operation. Mixing is an important unit operation in drug product manufacturing for compounding (dilution, pooling, homogenization, etc.). The current trend in adopting disposable bottom-mounted mixers has

Nanocomposite thin films for triggerable drug delivery.

Science.gov (United States)

Vannozzi, Lorenzo; Iacovacci, Veronica; Menciassi, Arianna; Ricotti, Leonardo

2018-05-01

Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion. Areas covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape. Expert opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.

Deep Learning for Drug Design: an Artificial Intelligence Paradigm for Drug Discovery in the Big Data Era.

Science.gov (United States)

Jing, Yankang; Bian, Yuemin; Hu, Ziheng; Wang, Lirong; Xie, Xiang-Qun Sean

2018-03-30

Over the last decade, deep learning (DL) methods have been extremely successful and widely used to develop artificial intelligence (AI) in almost every domain, especially after it achieved its proud record on computational Go. Compared to traditional machine learning (ML) algorithms, DL methods still have a long way to go to achieve recognition in small molecular drug discovery and development. And there is still lots of work to do for the popularization and application of DL for research purpose, e.g., for small molecule drug research and development. In this review, we mainly discussed several most powerful and mainstream architectures, including the convolutional neural network (CNN), recurrent neural network (RNN), and deep auto-encoder networks (DAENs), for supervised learning and nonsupervised learning; summarized most of the representative applications in small molecule drug design; and briefly introduced how DL methods were used in those applications. The discussion for the pros and cons of DL methods as well as the main challenges we need to tackle were also emphasized.

Update on Nanotechnology-based Drug Delivery Systems in Cancer Treatment.

Science.gov (United States)

Ho, Benjamin N; Pfeffer, Claire M; Singh, Amareshwar T K

2017-11-01

The emerging field of nanotechnology meets the demands for innovative approaches in the diagnosis and treatment of cancer. The nanoparticles are biocompatible and biodegradable and are made of a core, a particle that acts as a carrier, and one or more functional groups on the core which target specific sites. Nanotech in drug delivery includes nanodisks, High Density Lipoprotein nanostructures, liposomes, and gold nanoparticles. The fundamental advantages of nanoparticles are: improved delivery of water-insoluble drugs, targeted delivery, co-delivery of two or more drugs for combination therapy, and visualization of the drug delivery site by combining imaging system and a therapeutic drug. One of the potential applications of nanotechnology is in the treatment of cancer. Conventional methods for cancer treatments have included chemotherapy, surgery, or radiation. Early recognition and treatment of cancer with these approaches is still challenging. Innovative technologies are needed to overcome multidrug resistance, and increase drug localization and efficacy. Application of nanotechnology to cancer biology has brought in a new hope for developing treatment strategies on cancer. In this study, we present a review on the recent advances in nanotechnology-based approaches in cancer treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

On Demand Internal Short Circuit Device Enables Verification of Safer, Higher Performing Battery Designs

Energy Technology Data Exchange (ETDEWEB)

Darcy, Eric; Keyser, Matthew

2017-05-15

The Internal Short Circuit (ISC) device enables critical battery safety verification. With the aluminum interstitial heat sink between the cells, normal trigger cells cannot be driven into thermal runaway without excessive temperature bias of adjacent cells. With an implantable, on-demand ISC device, thermal runaway tests show that the conductive heat sinks protected adjacent cells from propagation. High heat dissipation and structural support of Al heat sinks show high promise for safer, higher performing batteries.

An implantable thermoresponsive drug delivery system based on Peltier device.

Science.gov (United States)

Yang, Rongbing; Gorelov, Alexander V; Aldabbagh, Fawaz; Carroll, William M; Rochev, Yury

2013-04-15

Locally dropping the temperature in vivo is the main obstacle to the clinical use of a thermoresponsive drug delivery system. In this paper, a Peltier electronic element is incorporated with a thermoresponsive thin film based drug delivery system to form a new drug delivery device which can regulate the release of rhodamine B in a water environment at 37 °C. Various current signals are used to control the temperature of the cold side of the Peltier device and the volume of water on top of the Peltier device affects the change in temperature. The pulsatile on-demand release profile of the model drug is obtained by turning the current signal on and off. The work has shown that the 2600 mAh power source is enough to power this device for 1.3 h. Furthermore, the excessive heat will not cause thermal damage in the body as it will be dissipated by the thermoregulation of the human body. Therefore, this simple novel device can be implanted and should work well in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

Modern Prodrug Design for Targeted Oral Drug Delivery

Directory of Open Access Journals (Sweden)

Arik Dahan

2014-10-01

Full Text Available The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options.

Evolutions in fragment-based drug design: the deconstruction–reconstruction approach

Science.gov (United States)

Chen, Haijun; Zhou, Xiaobin; Wang, Ailan; Zheng, Yunquan; Gao, Yu; Zhou, Jia

2014-01-01

Recent advances in the understanding of molecular recognition and protein–ligand interactions have facilitated rapid development of potent and selective ligands for therapeutically relevant targets. Over the past two decades, a variety of useful approaches and emerging techniques have been developed to promote the identification and optimization of leads that have high potential for generating new therapeutic agents. Intriguingly, the innovation of a fragment-based drug design (FBDD) approach has enabled rapid and efficient progress in drug discovery. In this critical review, we focus on the construction of fragment libraries and the advantages and disadvantages of various fragment-based screening (FBS) for constructing such libraries. We also highlight the deconstruction–reconstruction strategy by utilizing privileged fragments of reported ligands. PMID:25263697

Identification of designer drug 2C-E (4-ethyl-2, 5-dimethoxy-phenethylamine) in urine following a drug overdose

OpenAIRE

Van Vrancken, Michael J.; Benavides, Raul; Wians, Frank H.

2013-01-01

In recent years, access to information regarding acquisition and synthesis of newer designer drugs has been at an all-time high due largely to the Internet. As these drugs have become more prevalent, laboratory techniques have been developed and refined to identify and screen for this burgeoning population of drugs. This provides a unique opportunity for learning about many of these methods. Laboratory testing techniques and instrumentation are obscure to many health care professionals, yet t...

Management demands on information and communication technology in process-oriented health-care organizations: the importance of understanding managers' expectations during early phases of systems design.

Science.gov (United States)

Andersson, Anna; Vimarlund, Vivian; Timpka, Toomas

2002-01-01

There are numerous challenges to overcome before information and communication technology (ICT) can achieve its full potential in process-oriented health-care organizations. One of these challenges is designing systems that meet users' needs, while reflecting a continuously changing organizational environment. Another challenge is to develop ICT that supports both the internal and the external stakeholders' demands. In this study a qualitative research strategy was used to explore the demands on ICT expressed by managers from functional and process units at a community hospitaL The results reveal a multitude of partially competing goals that can make the ICT development process confusing, poor in quality, inefficient and unnecessarily costly. Therefore, from the perspective of ICT development, the main task appears to be to coordinate the different visions and in particular clarify them, as well as to establish the impact that these visions would have on the forthcoming ICT application.

A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials.

Science.gov (United States)

Yu, Yang; Teerenstra, Steven; Neef, Cees; Burger, David; Maliepaard, Marc

2016-04-01

The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. The study was designed as a retrospective reanalysis of existing studies. Nine replicate design bioequivalence studies representing six drug classes - i.e. for alendronate, atorvastatin, cyclosporin, ebastine, exemestane, mycophenolate mofetil, and ropinirole - were retrieved from the Dutch Medicines Regulatory Authority. In most studies, the intrasubject variability in total and peak drug exposure was comparable for the brand-name [in the range 0.01-0.24 for area under the concentration-time curve (AUCt ) and 0.02-0.29 for peak plasma concentration (Cmax ) on a log scale] and generic (0.01-0.23 for AUCt and 0.08-0.33 for Cmax ) drugs, and was comparable with the intrasubject variability upon switching between those drugs (0.01-0.23 for AUCt and 0.06-0.33 for Cmax ). The variance related to subject-by-formulation interaction could be considered negligible (-0.069 to 0.047 for AUCt and -0.091 to 0.02 for Cmax ). In the investigated studies, the variation in total and peak exposure seen when a patient is switched from a brand-name to a generic drug is comparable with that seen following repeated administration of the brand-name drug in the patient. Only the intrasubject variability seems to play a crucial and decisive role in the variation in drug exposure seen; no additional formulation-dependent variation in exposure is observed upon switching. Thus, our data support that, for the medicines that were included in the present investigation, from a clinical pharmacological perspective, the benefit-risk balance of a generic drug is comparable with that of the brand-name drug. © 2015 The British Pharmacological Society.

On the Trade-off Between Real-time Pricing and the Social Acceptability Costs of Demand Response

DEFF Research Database (Denmark)

da Silva, Hendrigo Batista; Santiago, Leonardo

2018-01-01

on the social acceptability costs of implementing demand response programs, and we discuss the key features of implementing a real-time price to energy. Although the literature acknowledges the existence of a social acceptability cost, it does not propose an explicit approach to dealing with this issue. A model...... for investigating the implications of the social acceptability cost is thus introduced and through it, we discuss thoroughly the joint impact of the elasticity and externality parameters on the tariff design of a demand response program. We explore how the increases in elasticity and in externality effects...... influence price changes in such programs and how the social acceptability cost could be reduced as a function of pricing policies. We conclude by discussing the policy design mechanisms in line with demand elasticity and their role in decreasing price variations to cope with the minimum volatility principle...

What is the Impact of Utility Demand Charges on a DCFC host

International Nuclear Information System (INIS)

Francfort, James Edward

2015-01-01

The PEV Electric Vehicle Supply Equipment (EVSE) delivered by The EV Project included both AC Level 2 and DCFC units. Over 100 of these dual-port Blink DC fast chargers were deployed by The EV Project. These DCFCs were installed in workplaces and in publicly accessible locations near traffic hubs, retail centers, parking lots, restaurants, and similar locations. The Blink DCFC is capable of charging at power up to 60 kW. Its dual-port design sequences the charge from one port to the other, delivering power to only one of two vehicles connected at a time. The actual power delivered through a port is determined by the PEV's on-board battery management system (BMS). Both the power and the total energy used to recharge a PEV can represent a significant cost for the charging site host. Many electric utilities impose fees for power demand as part of their commercial rate structure. The demand charge incurred by a customer is related to the peak power used during a monthly billing cycle. This is in contrast to the cumulative total energy usage that is the more familiar utility charge seen for most residential services. A demand charge is typically assessed for the highest average power over any 15 minute interval during the monthly billing cycle. One objective of The EV Project was to identify and elucidate the motivations and barriers to potential DCFC site hosts. The application of electric utility demand charges is one such potential barrier. This subject was introduced in the paper: DC Fast Charge - Demand Charge Reduction1. It discussed demand charge impact in general terms in order to focus on potential mitigation actions. This paper identifies specific cases in order to quantify the impact of demand charges on EV Project DCFC hosts.

What is the Impact of Utility Demand Charges on a DCFC host

Energy Technology Data Exchange (ETDEWEB)

Francfort, James Edward [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-06-01

The PEV Electric Vehicle Supply Equipment (EVSE) delivered by The EV Project included both AC Level 2 and DCFC units. Over 100 of these dual-port Blink DC fast chargers were deployed by The EV Project. These DCFCs were installed in workplaces and in publicly accessible locations near traffic hubs, retail centers, parking lots, restaurants, and similar locations. The Blink DCFC is capable of charging at power up to 60 kW. Its dual-port design sequences the charge from one port to the other, delivering power to only one of two vehicles connected at a time. The actual power delivered through a port is determined by the PEV’s on-board battery management system (BMS). Both the power and the total energy used to recharge a PEV can represent a significant cost for the charging site host. Many electric utilities impose fees for power demand as part of their commercial rate structure. The demand charge incurred by a customer is related to the peak power used during a monthly billing cycle. This is in contrast to the cumulative total energy usage that is the more familiar utility charge seen for most residential services. A demand charge is typically assessed for the highest average power over any 15 minute interval during the monthly billing cycle. One objective of The EV Project was to identify and elucidate the motivations and barriers to potential DCFC site hosts. The application of electric utility demand charges is one such potential barrier. This subject was introduced in the paper: DC Fast Charge - Demand Charge Reduction1. It discussed demand charge impact in general terms in order to focus on potential mitigation actions. This paper identifies specific cases in order to quantify the impact of demand charges on EV Project DCFC hosts.

Uncertainty analysis of daily potable water demand on the performance evaluation of rainwater harvesting systems in residential buildings.

Science.gov (United States)

Silva, Arthur Santos; Ghisi, Enedir

2016-09-15

The objective of this paper is to perform a sensitivity analysis of design variables and an uncertainty analysis of daily potable water demand to evaluate the performance of rainwater harvesting systems in residential buildings. Eight cities in Brazil with different rainfall patterns were analysed. A numeric experiment was performed by means of computer simulation of rainwater harvesting. A sensitivity analysis was performed using variance-based indices for identifying the most important design parameters for rainwater harvesting systems when assessing the potential for potable water savings and underground tank capacity sizing. The uncertainty analysis was performed for different scenarios of potable water demand with stochastic variations in a normal distribution with different coefficients of variation throughout the simulated period. The results have shown that different design variables, such as potable water demand, number of occupants, rainwater demand, and roof area are important for obtaining the ideal underground tank capacity and estimating the potential for potable water savings. The stochastic variations on the potable water demand caused amplitudes of up to 4.8% on the potential for potable water savings and 9.4% on the ideal underground tank capacity. Average amplitudes were quite low for all cities. However, some combinations of parameters resulted in large amplitude of uncertainty and difference from uniform distribution for tank capacities and potential for potable water savings. Stochastic potable water demand generated low uncertainties in the performance evaluation of rainwater harvesting systems; therefore, uniform distribution could be used in computer simulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

International Oil Supplies and Demands

International Nuclear Information System (INIS)

1991-09-01

The eleventh Energy Modeling Forum (EMF) working group met four times over the 1989--90 period to compare alternative perspectives on international oil supplies and demands through 2010 and to discuss how alternative supply and demand trends influence the world's dependence upon Middle Eastern oil. Proprietors of eleven economic models of the world oil market used their respective models to simulate a dozen scenarios using standardized assumptions. From its inception, the study was not designed to focus on the short-run impacts of disruptions on oil markets. Nor did the working group attempt to provide a forecast or just a single view of the likely future path for oil prices. The model results guided the group's thinking about many important longer-run market relationships and helped to identify differences of opinion about future oil supplies, demands, and dependence

International Oil Supplies and Demands

International Nuclear Information System (INIS)

1992-04-01

The eleventh Energy Modeling Forum (EMF) working group met four times over the 1989--1990 period to compare alternative perspectives on international oil supplies and demands through 2010 and to discuss how alternative supply and demand trends influence the world's dependence upon Middle Eastern oil. Proprietors of eleven economic models of the world oil market used their respective models to simulate a dozen scenarios using standardized assumptions. From its inception, the study was not designed to focus on the short-run impacts of disruptions on oil markets. Nor did the working group attempt to provide a forecast or just a single view of the likely future path for oil prices. The model results guided the group's thinking about many important longer-run market relationships and helped to identify differences of opinion about future oil supplies, demands, and dependence

International Oil Supplies and Demands

Energy Technology Data Exchange (ETDEWEB)

1991-09-01

The eleventh Energy Modeling Forum (EMF) working group met four times over the 1989--90 period to compare alternative perspectives on international oil supplies and demands through 2010 and to discuss how alternative supply and demand trends influence the world's dependence upon Middle Eastern oil. Proprietors of eleven economic models of the world oil market used their respective models to simulate a dozen scenarios using standardized assumptions. From its inception, the study was not designed to focus on the short-run impacts of disruptions on oil markets. Nor did the working group attempt to provide a forecast or just a single view of the likely future path for oil prices. The model results guided the group's thinking about many important longer-run market relationships and helped to identify differences of opinion about future oil supplies, demands, and dependence.

International Oil Supplies and Demands

Energy Technology Data Exchange (ETDEWEB)

1992-04-01

The eleventh Energy Modeling Forum (EMF) working group met four times over the 1989--1990 period to compare alternative perspectives on international oil supplies and demands through 2010 and to discuss how alternative supply and demand trends influence the world's dependence upon Middle Eastern oil. Proprietors of eleven economic models of the world oil market used their respective models to simulate a dozen scenarios using standardized assumptions. From its inception, the study was not designed to focus on the short-run impacts of disruptions on oil markets. Nor did the working group attempt to provide a forecast or just a single view of the likely future path for oil prices. The model results guided the group's thinking about many important longer-run market relationships and helped to identify differences of opinion about future oil supplies, demands, and dependence.

Bio-Inspired Multi-Functional Drug Transport Design Concept and Simulations.

Science.gov (United States)

Pidaparti, Ramana M; Cartin, Charles; Su, Guoguang

2017-04-25

In this study, we developed a microdevice concept for drug/fluidic transport taking an inspiration from supramolecular motor found in biological cells. Specifically, idealized multi-functional design geometry (nozzle/diffuser/nozzle) was developed for (i) fluidic/particle transport; (ii) particle separation; and (iii) droplet generation. Several design simulations were conducted to demonstrate the working principles of the multi-functional device. The design simulations illustrate that the proposed design concept is feasible for multi-functionality. However, further experimentation and optimization studies are needed to fully evaluate the multifunctional device concept for multiple applications.

A Study on the demands of research reactors and considerations for an export

Energy Technology Data Exchange (ETDEWEB)

Park, Cheol; Lee, Young Jun

2008-11-15

Among around 240 research reactors in operation over the world, around 80% have been operated for more than 20 years and 65% for more than 30 years. Hence the number of operable reactors is expected, between 2010 and 2020, to be reduced to 1/3 of the present situation if the lifetime of a research reactor is assumed to be 40 years. However, considering the recent re-highlighting of nuclear energy as a practical mass energy source and the contributions to the overall areas of science and technology, the demands for constructing a new research reactor and replacing the existing research reactors will be increased in the near future. On the other hand, vendors which participate in providing research reactors are not few, and AREVA in France and INVAP in Argentina are example of them in a positive position. Japan and Russia are regarded as potential competitors, but they do not actively appear in the market so far. Comparing those competitors with Korea, we have weak points regarding experiences on exports and the organizational systems as an integrated vendor. But we may have a competitiveness by grafting our experiences on the development of nuclear power technology and the construction and operation of the HANARO. In this report, the future potential demands for research reactors and the related considerations for exports have been surveyed and described, particularly, centering around the Netherlands, Vietnam and Thailand that are countries which may construct research reactors in the near future. Considerations for exporting a research reactor have been categorized into two groups of technical and nontechnical items. From a technical point of view, the issues on fuel and reactor type, design data and design ability, design codes, and technology property rights have been reviewed. For the non-technical items, an integrated project system, reasonable estimate of demands, social and economic conditions for potential demand countries, MOU status, nuclear non

A Study on the demands of research reactors and considerations for an export

International Nuclear Information System (INIS)

Park, Cheol; Lee, Young Jun

2008-11-01

Among around 240 research reactors in operation over the world, around 80% have been operated for more than 20 years and 65% for more than 30 years. Hence the number of operable reactors is expected, between 2010 and 2020, to be reduced to 1/3 of the present situation if the lifetime of a research reactor is assumed to be 40 years. However, considering the recent re-highlighting of nuclear energy as a practical mass energy source and the contributions to the overall areas of science and technology, the demands for constructing a new research reactor and replacing the existing research reactors will be increased in the near future. On the other hand, vendors which participate in providing research reactors are not few, and AREVA in France and INVAP in Argentina are example of them in a positive position. Japan and Russia are regarded as potential competitors, but they do not actively appear in the market so far. Comparing those competitors with Korea, we have weak points regarding experiences on exports and the organizational systems as an integrated vendor. But we may have a competitiveness by grafting our experiences on the development of nuclear power technology and the construction and operation of the HANARO. In this report, the future potential demands for research reactors and the related considerations for exports have been surveyed and described, particularly, centering around the Netherlands, Vietnam and Thailand that are countries which may construct research reactors in the near future. Considerations for exporting a research reactor have been categorized into two groups of technical and nontechnical items. From a technical point of view, the issues on fuel and reactor type, design data and design ability, design codes, and technology property rights have been reviewed. For the non-technical items, an integrated project system, reasonable estimate of demands, social and economic conditions for potential demand countries, MOU status, nuclear non

Assessment of precast beam-column using capacity demand response spectrum subject to design basis earthquake and maximum considered earthquake

Science.gov (United States)

Ghani, Kay Dora Abd.; Tukiar, Mohd Azuan; Hamid, Nor Hayati Abdul

2017-08-01

Malaysia is surrounded by the tectonic feature of the Sumatera area which consists of two seismically active inter-plate boundaries, namely the Indo-Australian and the Eurasian Plates on the west and the Philippine Plates on the east. Hence, Malaysia experiences tremors from far distant earthquake occurring in Banda Aceh, Nias Island, Padang and other parts of Sumatera Indonesia. In order to predict the safety of precast buildings in Malaysia under near field ground motion the response spectrum analysis could be used for dealing with future earthquake whose specific nature is unknown. This paper aimed to develop of capacity demand response spectrum subject to Design Basis Earthquake (DBE) and Maximum Considered Earthquake (MCE) in order to assess the performance of precast beam column joint. From the capacity-demand response spectrum analysis, it can be concluded that the precast beam-column joints would not survive when subjected to earthquake excitation with surface-wave magnitude, Mw, of more than 5.5 Scale Richter (Type 1 spectra). This means that the beam-column joint which was designed using the current code of practice (BS8110) would be severely damaged when subjected to high earthquake excitation. The capacity-demand response spectrum analysis also shows that the precast beam-column joints in the prototype studied would be severely damaged when subjected to Maximum Considered Earthquake (MCE) with PGA=0.22g having a surface-wave magnitude of more than 5.5 Scale Richter, or Type 1 spectra.

Glutamic acid and its derivatives: candidates for rational design of anticancer drugs.

Science.gov (United States)

Ali, Imran; Wani, Waseem A; Haque, Ashanul; Saleem, Kishwar

2013-05-01

Throughout the history of human civilizations, cancer has been a major health problem. Its treatment has been interesting but challenging to scientists. Glutamic acid and its derivative glutamine are known to play interesting roles in cancer genesis, hence, it was realized that structurally variant glutamic acid derivatives may be designed and developed and, might be having antagonistic effects on cancer. The present article describes the state-of-art of glutamic acid and its derivatives as anticancer agents. Attempts have been made to explore the effectivity of drug-delivery systems based on glutamic acid for the delivery of anticancer drugs. Moreover, efforts have also been made to discuss the mechanism of action of glutamic acid derivatives as anticancer agents, clinical applications of glutamic acid derivatives, as well as recent developments and future perspectives of glutamic acid drug development have also been discussed.

First drop dissimilarity in drop-on-demand inkjet devices

International Nuclear Information System (INIS)

Famili, Amin; Palkar, Saurabh A.; Baldy, William J. Jr.

2011-01-01

As inkjet printing technology is increasingly applied in a broader array of applications, careful characterization of its method of use is critical due to its inherent sensitivity. A common operational mode in inkjet technology known as drop-on-demand ejection is used as a way to deliver a controlled quantity of material to a precise location on a target. This method of operation allows ejection of individual or a sequence (burst) of drops based on a timed trigger event. This work presents an examination of sequences of drops as they are ejected, indicating a number of phenomena that must be considered when designing a drop-on-demand inkjet system. These phenomena appear to be driven by differences between the first ejected drop in a burst and those that follow it and result in a break-down of the linear relationship expected between driving amplitude and drop mass. This first drop, as quantified by high-speed videography and subsequent image analysis, can be different in morphology, trajectory, velocity, and volume from subsequent drops within a burst. These findings were confirmed orthogonally by both volume and mass measurement techniques which allowed quantitation down to single drops.

Performance Analysis of On-Demand Routing Protocols in Wireless Mesh Networks

Directory of Open Access Journals (Sweden)

Arafatur RAHMAN

2009-01-01

Full Text Available Wireless Mesh Networks (WMNs have recently gained a lot of popularity due to their rapid deployment and instant communication capabilities. WMNs are dynamically self-organizing, self-configuring and self-healing with the nodes in the network automatically establishing an adiej hoc network and preserving the mesh connectivity. Designing a routing protocol for WMNs requires several aspects to consider, such as wireless networks, fixed applications, mobile applications, scalability, better performance metrics, efficient routing within infrastructure, load balancing, throughput enhancement, interference, robustness etc. To support communication, various routing protocols are designed for various networks (e.g. ad hoc, sensor, wired etc.. However, all these protocols are not suitable for WMNs, because of the architectural differences among the networks. In this paper, a detailed simulation based performance study and analysis is performed on the reactive routing protocols to verify the suitability of these protocols over such kind of networks. Ad Hoc On-Demand Distance Vector (AODV, Dynamic Source Routing (DSR and Dynamic MANET On-demand (DYMO routing protocol are considered as the representative of reactive routing protocols. The performance differentials are investigated using varying traffic load and number of source. Based on the simulation results, how the performance of each protocol can be improved is also recommended.

Psychiatric aspects of designer drugs and new psychoactive substances consumption

Directory of Open Access Journals (Sweden)

Antsyborov A.V.

2017-02-01

Full Text Available according to the authors, appeared not long ago new psychoactive substances (designer drugs, including synthetic cannabinoids, derivatives of cathinone, phenethylamines, new stimulants, synthetic opioids, tryptamine derivatives, phencyclidine, piperazine, agonists of GABA (A/B receptors have become a serious problem for both consumers and doctors. Consumers of these substances are attracted primarily by the intensity of psychoactive effects, as well as «legal purity», which is declared by shadow producers. This indicates that there are some significant difficulties of laboratory typing of new surfactants. Designer drugs when ingested, can affect a range of neurotransmitter pathways/receptors: dopamine, cannabinoid (CB1, GABA(A/B, 5-HT2A, glutamate, and k-opioid receptors (KOR, the imbalance of which leads to the development of polymorphic psychotic disorders.

Demand Response Integration Through Agent-Based Coordination of Consumers in Virtual Power Plants

DEFF Research Database (Denmark)

Clausen, Anders; Umair, Aisha; Ma, Zheng

2016-01-01

of industrial loads. Coordination happens in response to Demand Response events, while considering local objectives in the industrial domain. We illustrate the applicability of our approach on a Virtual Power Plant scenario with three simulated greenhouses. The results suggest that the proposed design is able...... Power Plant design that is able to balance the demand of energy-intensive, industrial loads with the supply situation in the electricity grid. The proposed Virtual Power Plant design uses a novel inter-agent, multi-objective, multi-issue negotiation mechanism, to coordinate the electricity demands...... to coordinate the electricity demands of industrial loads, in compliance with external Demand Response events....

Strategic and Tactical Design of Competing Decentralized Supply Chain Networks with Risk-Averse Participants for Markets with Uncertain Demand

OpenAIRE

Hafezalkotob, Ashkan; Makui, Ahmad; Sadjadi, Seyed Jafar

2011-01-01

An integrated equilibrium model for tactical decisions in network design is developed. We consider a decentralized supply chain network operating in markets under uncertain demands when there is a rival decentralized chain. The primary assumption is that two chains provide partial substitutable products to the markets, and markets' demands are affected by tactical decisions such as price, service level, and advertising expenditure. Each chain consists of one risk-averse manufacturer and a set...

Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution.

Science.gov (United States)

Clewe, Oskar; Karlsson, Mats O; Simonsson, Ulrika S H

2015-12-01

Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs.

Pu-recycling in light water reactors: calculation of fuel burn-up data for the design of reprocessing plants as well as the influence on the demand of uranium

International Nuclear Information System (INIS)

Gasteiger, R.

1977-02-01

This report gives a detailed review on the composition of radionuclides in spent LWR fuel in the case of Pu-recycling. These calculations are necessary for the design of spent fuel reprocessing plants. Furthermore the influence of Pu-recycling on the demand of uranium for a single LWR as well as for a certain growing LWR-population is shown. (orig.) [de